Final Report Summary - LIGHT+TER (Development of a compact, low-cost and easy-to-use device based on LED technology for non-invasive selective haemostasis to benefit coagulation problems)
Executive summary:
LIGHT+TER project aims to develop a new range of low-cost and easy-to-use medical devices able to induce coagulation in superficial wounds, in all the cases where a rapid and effective haemostasis is required. The project thus addresses both a public health problem, i.e. coagulation disorders, typical of hereditary diseases like haemophilia (40 000 people affected in the European Union (EU)-27), or induced by use of specific anti-coagulant drugs (20 million people in EU-27) and the needs of a wide category of people as children or elderly population for whom even small superficial brushes may need a fast intervention. Bleeding problems in general have a strong impact on the quality of life. Even small medical interventions, as dental surgery for example, pose important problems for these patients, requiring the suspension of the anticoagulant therapy days before the surgery, with the consequent risk of having a relapse of the cardiovascular problem. In this framework, there is a technological need for a cheap, safe and easy to handle tool to help blood coagulation, to be used directly by the patient or by low-specialised personnel. Starting from this social need, the emerging optoelectronics technologies can offer a possible solution, as the use of miniaturised and non-invasive devices based on optoelectronics that exploit the properties of light to bring about certain effects is becoming more and more diffuse, especially for micro-surgery, dermatologic treatments, ophthalmology and plastic surgery.
The final goal of LIGHT+TER project was to address this need through the development of a compact and easy to use medical device based on light-emitting diode (LED) technology, able to induce haemostasis of skin blood vessels without damaging the surrounding tissues. The main mechanism at the basis of LIGHT+TER project is photo-thermo haemostasis (conversion of radiant energy to heat by haemoglobin that results in thermal denaturation of blood) which up to date has been realised only through very expensive, bulky and complex laser sources. LIGHT+TER project, starting from the concept at the basis of a patent owned by the small and medium-sized enterprise (SME) partner Light4Tech, aims at demonstrating the use of low cost LEDs to induce non-invasive photo-thermal coagulation, and developed two prototypes of medical device that could be configured both as an over-the-counter product and as an ambulatory tool (e.g. dental surgery).
These two prototypes are the basis for two commercial products to be optimised in the future, providing a good opportunity for the 34 500 SMEs active in EU in the biomedical sector to gain market share in medical device market with an innovative range of products with important commercial perspectives.
Although the original target end users for the LIGHT+TER devices were people with coagulation diseases, the consortium evaluated also other customer segments in order to show that the market perspectives for the device go beyond these specific groups of patients.
From the economical point of view, by developing a LED-based medical device for the haemostasis of superficial capillary vessels, LIGHT+TER addresses two sub-sectors of the medical device market:
- Wound care device market, including products like mechanical staples or sutures for wound closure, dressings or bandages for wound care, surgical sealants, adhesives and topical absorbable haemostats.
- Laser-based medical device market, mainly used in microsurgery, ophthalmology, dental applications and dermoplastics.
Aiming at a market penetration of 2 % after 5 years after the project completion, with a potential market of about EUR 200 million.
Project context and objectives:
The main goal of the LIGHT+TER project is to develop a innovative medical device based on LED technology for non-invasive haemostasis to benefit specific categories of people as children or elder population or people suffering from coagulation problems, for whom even small superficial brushes may need a fast intervention.
A large number of coagulation disorders that makes the haemostasis process difficult, impact negatively on the quality of life and require attention in normal daily living. Even superficial wounds in the first layers of the skin may become a problem for specific groups of people, due to the difficulty in coagulation. People with heamostasis problems may incur in severe bleeding even after a small abrasion and they need to fall into specific procedures when they have to undertake a minor surgery, as for example a dental surgery, dermatologic treatments or ambulatory therapies. Among people with coagulation problems, together with people with specific hereditary diseases, are the 20 million people in Europe who assume anticoagulants that, making blood more fluid, can also cause problems in haemostasis process.
In order to avoid the difficulties described above, there is the technological need for a cheap, safe and easy-to-use device to speed up blood coagulation that can be used directly by the patient or by low-specialised medical personnel.
To better understand how the device developed within the LIGHT+TER project works, it is worth examining the heamostasis process.
The haemostasis of blood vessels can be achieved by three main methodologies, local mechanical compression, pharmacological treatment, or thermal coagulation.
Electrocoagulation and photocoagulation, both thermal coagulation techniques, can be used in order to transfer heat to the wound blood vessels. Electrocoagulation is used in surgical applications to treat haemorrhage, like bleeding ulcers, and to ablate tumours, mucosal lesions and even refractory arrhythmias. The major disadvantage in the use of this technique is that it is not selective: the heating induced by the electrical current in fact involves also the surrounding tissues close to the vessels, producing as a side effect the presence of unsightly burns on the treated skin. Moreover, the needed instrumentation is difficult to be transferred to out-of-hospital applications, and the risks connected to its use make it impossible to be used in self-medication.
The photocoagulation technique consists in the light radiation of the tissue. At the state of the art, laser is the most common light source used in biomedical devices. In recent decades the use of medical devices based on laser as for example in dermatologic laser surgery has dramatically increased. When radiation hits the skin, it may be reflected, transmitted, or absorbed. Absorbed energy is mostly responsible for the clinical effect due its thermal energy conversion through absorption of several skin components, like blood, water and melanin. The use of extremely high power and concentrated radiation, as in the case of laser used as photocoagulator, the treatment induces collateral damage because typically the light is not selectively absorbed by a single chromophore, but heats also the surrounding tissue and creating collateral effects as hyperpigmentation and hypopigmentation. In order to reduce undesired collateral damages induced by use of laser, the selective photothermolysis based on Anderson and Parrish's theory has been recently introduced.
This theory states that selective heating of a target chromophore is achieved when the laser wavelength is preferentially absorbed by the chromophore, the energy of the laser is high enough to damage the chromophore, but the pulse duration of laser energy is shorter than the thermal relaxation of the target. The majority of cutaneous treatment based on lasers in use today operate according to these principles and attempt to limit the duration of the laser light that reach the tissue. The use of laser light with the property to be selectively absorbed only by haemoglobin has the disadvantage to be very expensive and frequent maintenance interventions are need.
To overcome all the technological limitations of the photocoagulation devices based on lasers, the development of a new cheap, compact and easy-to-use photocoagulation device based on the emerging optoelectronics technologies, as high power LED sources, able to induce haemostasis of skin blood vessels through a selective photo-thermo-coagulation process is thus highly desirable.
The mechanism at the basis of LIGHT+TER project is photo-thermal haemostasis, that is the conversion of light energy into heat due to selective absorption by (de)oxyhaemoglobin and subsequent heat diffusion in order to obtain thermal denaturation of blood and vascular tissue. The appropriate selection of the LED light wavelength that ensures the selectivity of the process, in particular the specific absorption wavelength of the light by haematic components, as haemoglobin, ensures that the light interacts only with the blood components and not with the surrounding tissues guaranteeing the minimum invasivity of the technique. The technique is based on a patent 'LED device for blood vessel haemostasis', owned by SME partner Light4Tech, in which the novel concept of photocoagulation is demonstrated using incoherent ultraviolet (UV) radiation. Using light with wavelength in the range 400 - 450 nm, radiation power between 0.5 and 1 W and an exposure time of about 1 minute is possible induce photocoagulation on bleeding superficial wound, as demonstrated through an extensive testing by Light4Tech in cooperation with LENS and CNR, using large and cumbersome laboratory light source equipment projecting UV radiation on animal wounds. In particular the testing performed by Light4Tech demonstrated that the wound exposed to the light heals faster than a wound unexposed.
There are consistent advantages using LEDs instead of lasers, in particular the LED sources are more compact, allowing for the possibility to develop a portable device, have low energy consumption enabling the use of batteries and, last but not the least, they are definitely cheaper than laser sources allowing for the development of an over-the-counter product. The use of LED source is also safer than the laser source both for the patient and operator, and the recent advancements in LED technology, in particular the increase of the optical emitted power up to 1 Watt, in the close ultraviolet (390 - 470 nm), where haemoglobin has the maximum optical absorption peak, allow the technical feasibility of the intended device. The LIGHT+TER project aimed to further develop the patented concept by Light4Tech, thus demonstrating the use of low cost LED source to induce photo-thermal haemostasis, in two possible layouts.
In the layout no 1, the photocoagulator will have the appearance of small torch, in order to be easily manageable and will be powered through a rechargeable battery, ensuring the portability of the system, for example in first-aid applications. The portable device is identified as 'self-medication' device to be sold as an over-the-count product, and will be used in conjunction with a biodegradable polymeric plaster transparent to UV-blue light, that will serve as interface between the wounded skin and the LED light source, in order to avoid any type of bacterial contamination.
The layout no 2 consists in an ambulatory version of the device, in which the optical fibre is used to transmit the LED radiation, in order to be used by specialised personnel for ophthalmologic, dental, micro-surgery and plastic surgery applications.
The devices are composed by the following components:
(a) LED-based source, based on LED source with emission in the close UV region, with total power in the range 0.5 - 1 W, enough to induce haemostasis;
(b) the electronics, for the management of the LED source in order to control the emitted optical power, for the switch on / off operations, for control of user interface display and power supply;
(c) the optical system, able to focus the LED light on the skin in the case of layout no 1, and in an optical fibre in the layout no 2.
Regarding the practical use of the LIGHT+TER device, the portable device (layout no 1) is intended to be adopted in first-aid situations, in order to stop the superficial abrasions bleeding and its use consist in the application of the LED light directly onto the skin where bleeding occurs.
To ensure a sterile interface between the wound and the portable device, a specific plaster, made of a biocompatible and biodegradable material transparent to the LED wavelength has been developed. The optical fibre device (layout no 2), is intended to be used in hospital environments by specialised personnel for ambulatory applications.
However in order to bring this concept into a working hand-held able system, the following objectives had to be achieved:
(a) replacement of the UV lamp with compact and cheap LED source;
(b) design and development of focusing optical system that is also able to focus LED light into an optical fibre;
(c) design and implementation of a compact and miniaturised control electronics and power supply for the devices;
(d) identification of a polymeric material for the biodegradable plaster, transparent to the UV-blue light;
(e) set-up of a model of the interaction between light and polymeric material of the plaster in order to provide the LED light propagation into the different structures of the skin.
Beyond the project, major goal of the partners will be of course to achieve a CE mark for the final product, conducting the required clinical validation. Commercial versions of the devices are expected to be ready within 12 - 18 months from the end of LIGHT+TER project in order to be inserted in the biomedical market.
Project results:
During the duration of LIGHT+TER project, started on 1 January 2010 and finished on 31 December 2011, the activities have generated the following results:
(a) application of LED technology to induce haemostasis;
(b) control electronics;
(c) disposable plaster;
(d) optical setup for micro-surgical applications;
(e) LIGHT+TER device integration.
In the following, the above mentioned results and the activities performed to achieve them will be described in detail.
Application of LED technology to haemostasis
After the identification of the technical requirements of the LIGHT+TER devices taking into account all optic, physic and electronic aspects, three parallel but strongly interconnected research lines were started, one dedicated the LED-based source and optical system definition and design, one dedicated to the control and User-interface electronics and another one on the biodegradable plaster.
During the activities of design and development of the LED-based optical system, the consortium has developed the light-tissue interaction model, defined and tested the LED source and developed the optical system for the portable device.
Concerning the light-tissue interaction, a model based on the finite element method (FEM) has been developed and used to fix and verify the parameters required to induce haemostasis through the photothermal effect. After the theoretical treatment on the light-tissue interaction, human skin physics and optical properties, we have moved to a discussion on mathematical models. In particular, various mathematical models have been developed to study light / tissue interactions and to predict optimal light source parameters to achieve high-efficacy light-based treatment or diagnostics procedures. In all of these models, the biological tissue and in particular the skin, is considered as an optically turbid medium. The best solution for analysing through a model the light-tissue interaction is the use of the FEM, with which is possible to solve contemporarily more than one partial differential equations, studying the solution in space and time. This goal may be achieved with commercial software developed to solve multiphysics problems. Among the software that are commercially available, only the Comsol Multiphysics (produced by Comsol AB, Stockholm, Sweden) had the characteristics that enabled a user-friendly approach to this complex problem, and it was chosen to describe this particular light tissue interaction both in space and time. Moreover, the reliability of this FEM analysis of photothermal processes has been already proved by previous studies that combined the predictive analysis with experimental measurement of the temperature and histological and morphological analysis of the treated tissues. Aim of the modelling study of light / tissue interaction, is to indicate a light wavelength region were light absorption is localised in the blood content of the tissue and predominantly converted into a heat effect. The induced temperature and treatment time has to be optimised in order to induce coagulation in the blood fraction of the tissue, while the healthy tissue has not to be affected by irreversible thermal damage. Moreover, different irradiation conditions have to be tested, in order to indicate the best conditions to be designed. The modelling study of light / skin interactions evidenced that blue light sources may be used to induce a selective photothermal effect in the skin. The proposed approach is a possible solution for coagulation of superficial bleeding, as it induces a localised effect in the blood region in question without having any significant collateral effects on the surrounding tissues. The selective photo-thermal coagulation may be induced with the light source in close contact with the tissue. From this theoretical study, it has been pointed out that we could induce high temperatures inside the tissue, able to induce photocoagulation of superficial capillaries without inducing irreversible damages to adjacent tissue. The best wavelength to be used is in the range 400 - 450 nm. The best treatment time using a LED source with central wavelength at 405 nm with 300 mW of power output is 30 s, by keeping the LED surface in close contact with the tissue. The active area considered is 8 mm in diameter. In this conditions, a photocoagulator may be designed.
Concerning the LED-based source, once the main parameters derived from the light-tissue interaction have been obtained, it was possible to define a list of sources that could be taken into account for the device development. The LED sources that best fit the required performances for the LIGHT+TER device are produced by the company Roithner LaserTechnik (RLT) (see http://www.roithnerlaser.com/(odnośnik otworzy się w nowym oknie) online for further details) from Vienna, Austria. The best LEDs for our scope are models LED405-66-60 and LED435-66-60. The model LED405-66-60 emits 300 mW of optical power at 405 nm emission peak, while LED435-66-60 emits 720 mW of optical power at 435 nm emission peak. High power LED source with emission peak at 415 nm is also available, but it does not provide enough optical power to induce haemostasis (the minimum required power is 300 mW, as derived from the light-skin interaction model). Both LED sources were tested to check the optical properties of optical power emitted that the wavelength spectrum. The tests have confirmed that the LED sources identified are the best source for the self-medication layout in term of wavelength and optical power. As regards the LED-based source for the optical fibre layout, the LED source that best fit the required performances is the model Luxeon Rebel Royal Blue star (LXML-PR01-0500) produced by the company Lumileds, which emits 875 mW of optical power at 447.5 nm emission peak. Each LED source indicated above was coupled and tested with an optical system for managing the angular divergence of the incoherent light of the LED. In particular for the LED by RLT, for the portable device, has been tested in combination with optical system model TO-18, which named LED aspheric glass lens, with a diameter of 18 mm and focal distance of 13.5 mm, while for Rebel LED was used the model Carclo LED fibre coupling with focal distance of 20 mm.
Control electronics
The aim of the control electronics activities was to design and develop the miniaturised electronic board for the control and management of the LED source, providing the correct power supply and setting of the optical power emitted, together with the development of the electronics for the user interface. For the portable device, battery powered, a step-up current feedback converter is required, because the LED module operates at 18 V, driving 250 mA. It is very difficult to obtain such voltage directly from commonly available rechargeable batteries. After some battery endurance tests the chosen battery configuration is 4 x 1.2 V AA rechargeable Ni-MH batteries. The device could continuously operate for 2-3 hours from 2 400 mAh batteries AA type. Using smaller footprint AAA batteries (1 000 - 1 200 mAh typically) the device could operate continuously for about 1 hour. Typical light burst is estimated at 20 second length, about 500 applications before of complete discharge of the AA batteries, while with type AAA batteries is possible to reach 200 applications with a charge cycle.
The power converter is based on MC34063 chip, a simple and reliable boost converter, with about 80 % conversion efficiency and current feedback. The power converter footprint is only 3 x 2cm on the printed circuit board. This step-up power converter design ensures constant 250 mA current flowing through LED module, even if its voltage drop changes e.g. by temperature change. It is controlled by single ENABLE signal, connected to the microchip controlling the user interface for easy switch. The first version of the user interface has been designed according to the specifications fixed by technical requirements report. It is composed from two 7 segment display for elapsed time, 2 colour red/green LED diode for battery status and two pushbuttons: TIME and START. Pushing the TIME button adds 10 seconds to the timer and START enables the lighter and triggers the countdown. After 10 seconds of inactivity, either after finishing countdown or just not triggering START, the device returns to power down mode, in order to avoid the discharge battery. Battery status is shown using two-colour LED, changing its colour from green, thought yellow, to red. Thanks to the flexible microcontroller design it is possible to program any other user interface mode. With such user interface, the whole electronic could be assembled on a small circuit board measuring about 3 x 5 cm (with batteries in the external case). Prototype built on designed printed circuit board (PCB) using surface-mount device (SMD) technology could be much smaller and fit to any design of the plastic cover.
For the optical fibre layout, through microcontroller programme, the button functions have been reconfigured to serve START and STOP functions. After pressing START button the display shows elapsed time since start event. Switching from portable layout mode to optical fibre layout mode is a matter of loading different firmware to the microcontroller. In the final product firmware will be protected. For the development of the prototype, the microcontroller Attiny26, a low cost AVR core microcontroller manufactured by Atmel, has been chosen.
Concerning the miniaturised and final version of control electronic, in order to reduce and optimise the spatial dimension of the electronic PCBs, we have chosen to design two modules, the main module, named L+T-M, with microcontroller and LED diode driver, and the display module, named L+T-D, with 3-digit display. The main module L+T-M is common to the two versions of the device, which differ only for the components soldered, while the display module, named L+T-D, will be present only in the optical fibre device. Two versions of the L+T-M module and one version of the L+T-D module have been realised.
The portable version of the LIGHT+TER device comprises only the main module L+T-M, with the electronic component able to manage the power supply by batteries compartment. In this version the connector BAT is used to plug the battery power supply, while the power LED module driver is based on the integrated circuit MC34063ABD that is the core of step-up converter. Its operation is controlled with the ENABLE signal, which in high state turns on the driver, and in low state turns it off. The second integrated circuit, microcontroller ATtiny26IA-SU, apart from controlling the driver, monitors the battery supply voltage, reads the state of the pushbutton and controls up to two LED diodes operating as indicators. The pushbutton and these diodes are connected to the J1 connector, which is also used for programming the microcontroller in case it is needed to change the configuration of the device. The bill of materials of the L+T-M module for the portable device has been done together with an assessment of the production costs of the PCB for the portable device.
The optical fibre version of the LIGHT+TER device comprises a L+T-M module, with the electronic component able to manage the power supply by + 5 V direct current (DC) power supply, and a L+T-D module. The module L+T-M is equipped with connector PSU, which gets the power from external 5V power supply unit. Diodes D2, D3 and transistor Q2 form a supply switching circuit, which selects the external power supply, when present, or the batteries otherwise. Voltage from the PSU connector is also passed directly to microcontroller ATtiny26IA-SU, so that it can determine whether it is running on the external supply or batteries. In this version, the microcontroller ATtiny26IA-SU manages the display on the L+T-D module as well. The connection between the two modules is provided by a 10-wire, pitch 1.27 mm ribbon cable, from header J2 on L+T-M module to J1 on L+TD. Module L+T-D comprises a BCD to 7-segment display decoder and a triple 7 segment display. The microcontroller sets a logic level in order to set the number 0-9 on 3-digit display. Quickly sweeping through all three positions of the display, the microcontroller can make a three digit number visible. The bill of materials of the L+T-M and L+T-D modules for the optical fibre device was prepared and the production costs of the PCBs were assessed.
Disposable plaster
After a careful examination on the state of the art on biodegradable polymers, the consortium has developed a light-polymer interaction model, based on FEM, verifying the interaction of the biodegradable polymers with the blue light in order to select the material satisfying the requirements, also in terms of biodegradability, flexibility and transparency to UV-blue light. Was also studied the dependence of the transparency to UV-blue light as a function of film thickness used as interface between the device and bleeding wound. The choice fell on polylactic acid (PLA) and the study on the extrusion process of PLA films has been carried out, taking into account the physical and mechanical characteristics of the material. A biodegradable plaster prototypes based on PLA has also been realised. The biodegradable plaster must ensure a safe interface between the injured skin and the portable LIGHT+TER device during application. The prototype are based on the PLA film, which is transparent to the wavelengths required for haemostasis, and are surrounded by an adhesive part similar to a standards patch to ensure a good contact with the skin. It is worth noting that the plaster has to remain in contact with the skin only for the time of application required for haemostasis which is below one minute: for this reason, it is not necessary to have a very strong adhesive. Two sizes have been chosen (10 x 8 and 5 x 7 cm), to facilitate the use also in case of larger wounds, without replacing the plaster between two applications of the device on two parts of the wound.
Optical setup for micro-surgical applications
The optical setup for micro-surgical applications comprises the optical fibre connector to the LED source and the choice of the appropriate optical fibre, that can be used in the optical fibre LIGHT+TER device. The choice of the optical fibre has been done taking into account several characteristics. The fibre core material were chosen in plastic for their low cost and the possibility to be disposable. various plastic optical fibres are available on the market, the choice has been made considering the transmission of the fibres in the UV-blue region of the spectrum. Since the fibre diameter affects the angular emission and the maximum optical power available in the irradiated area to induce photo-haemostasis, during the activities plastic optical fibres of various diameters have been tested. The fibre tested are constituted by inner core of polymethyl methacrylate (PMMA) resin and a cladding of Fluorinated polymer, with global fibre diameter of 1 mm, 1.5 mm, 2 mm and 3 mm, and a length of 0.8 m.
In order to perfectly coupling the LED source and the plastic optical fibre, a mechanical mount has been developed, to centre the axis of optical propagation of the two components. The two parts, together with the LED source and the optical fibre, represent the prototype light source for the optical fibre layout. Figure 9 shows the mechanical rail to mount the LED on its heatsink, because the heatsink will represent the mechanical reference to centre the optical fibre respect to LED.
The first mount is constituted by a rail with a fixed part, in blue, and a moving part, in green. The fixed part works as holder for the heatsink of the LED source; the moving part is properly shaped to fit the holes located in the six corners of the hexagonal PCB of the LED source, as depicted in Figure 10. This mount serves to fix the LED source centred and aligned with respect to its heatsink.
It is made with two cylindrical coaxial mechanical mounts. The former mount allows to fix on it the LED source, together with the heatsink, the lens holder and the focusing optics. The latter mount, indicated in gold, works as a holder for the plastic optical fibre and it can be inserted in the former mount allowing proper positioning with respect to the optical system and LED source, maximising the optical coupling.
This optical-fibre connector and relative fibres with different diameter have been tested, in order to check the optical power at fibre output. The plastic optical fibres were all tested with the LED source equipped with focalisation apparatus and the optical fibre placed in the focus of the focalisation apparatus itself. The optical power irradiated at the fibre output was measured, together with the typical angular emission. The LED source was mounted on its mount together with the focalisation apparatus, the dedicated heatsink and supplied with a variable DC current. The current was varied in the range between 50 mA up to 1 000 mA with steps of 50 mA. The plastic optical fibres were placed in the focus of the focalisation apparatus and bent with a radius of curvature of approximately 10 cm. The fibre output was placed in front of a power meter OPHIR model PD300-3W. The emitted power at the fibre output was measured versus the input current flowing in the LED source. The angular emission was evaluated by measuring the angular profile of light emitted at the fibre output.
In order to compare the plastic optical fibres tested and to find the optimal solution for the optical fibre layout, the characteristics of maximum power density and angular emission has been considered.
The results provided by the test has been used as input for the theoretical model of light-tissue interaction, developed for the LIGHT+TER project. The model has been used to verify the photo-haemostatic capability of the optical fibre layout. The theoretical simulations have been done using 447 nm as excitation wavelength, corresponding to the central emission wavelength of the rebel LED source, and an emitted optical power with angular emission corresponding to the data measured for different plastic optical fibres tested. The theoretical simulations have been done considering the optical fibre output located at a distance of 1 mm from the tissue to be irradiated. According to the photohaemostasis model of the light and skin interaction, in all the configuration cases examined, the power density available at the fibre output is enough to perform photo-haemostasis, albeit with different irradiation time. The most comforting result is that for all the optical fibre configurations the temperature at which the denaturation process is triggered is achieved, activating photohaemostasis, although the size of the illuminated area differ. In particular, the fibre with diameter up to 1.5 mm, requires irradiation time beyond 30 seconds to reach temperatures around 70 - 80 degrees of Celsius, while the fibre with 2 mm diameter, after 5 seconds of irradiation already reached the temperature above which it begins to produce damage at the surrounding tissue. The choice of the best fibre configuration depends on the extension of the illuminated area and on the speed of the application required.
LIGHT+TER device integration
The LIGHT+TER devices integration started with the plastic case design and continued with the integration of all the sub-parts to obtain two device prototypes. The portable case device is made of four different parts each designed to be easily connected with each other without the use of screws or additional components. The internal space was optimised to keep the overall dimensions low, having the final dimensions of 140 x 56 x 50 mm (LxWxH), suitable for easy handling and use by different users / patients. The portable case was also designed to have no edges and to avoid getting hurt while it is handled.
Furthermore, the material is also sufficiently resistant to not shatter when the case is dropped. The bottom case part constitutes the main body, where most of the device internal components are mounted to it, the first case component to be mounted is the top case part which connects to the bottom case by snap-in connections. The battery compartment case part has the same connection method as the top case, and joins with both the top and bottom case parts. To disconnect the components from each other, the snap-in connections can be released be pressing on the levers using a thin object such as a screwdriver. The portable case has two distinct compartments in which all the components are firmly mounted. The right area includes the power supply of the portable device, constituting of three AA batteries and electric terminals, while on the left side there is the PCB with all the connections, push button, optical lens, LED source and its heatsink.
The case design of the optical fibre version has different features with respect to the portable case design. However, the design process followed the same targets defined for the portable case where the case had to be lightweight, ergonomic, and safe. Since the tabletop device is based on fibre optics, it has different components compared to the portable device and the final dimensions are 100 x 110 x 80 mm (LxWxH). The tabletop case is made of two main parts: a top part and a bottom part. The two parts connect using snap-in connections which tightly join the two case parts without the need of screws. The front part has visible all the fundamental elements necessary for the user, including the display, to operate the device. The display digit is placed at a 45-degree angle being suitable for reading it when the user is either sitting at the desk or standing up. On the left side of the display there is a coloured LED indicator which has the purpose to notify the user when the system is receiving power and ready to operate. On the other side of the display there is a round push button which starts and stops the operation of the system when pressed. Once this button is released, the display will start counting the operation time elapsed. On the case in the rear side there are the switch to turn ON the device and a power connector, which receives electricity from the socket on the wall. The PCB for the tabletop device was positioned to easily connect the internal components. In the tabletop device, there are two PCBs mounted to the case, the first is the main PCB, being the same for the portable device, and the second PCB was designed to manage the display. The optical fibre connector is mounted to the case without screws. A hole at the front of the case was also added to allow the passage of the optical fibre through the case.
The prototype cases, the LEDs source and the electronic PCBs in its miniaturised version have been integrated to construct the LIGHT+TER devices prototypes.
The tests on the prototypes confirmed that the overall performances of devices are the same of the single subparts.
Potential impact:
Although the main target end users for the LIGHT+TER devices indicated in the Description of Work are people with coagulation diseases, such as haemophilia or other diseases, it is not possible to prove without specific in vivo tests, not foreseen within the project, that some specific clinical conditions occurring in these patients do not interfere with photocoagulation process at the basis of the intended device.
In this framework, it is worth evaluating other possible customer segments, in order to show that the application fields and market perspectives for the LIGHT+TER device go beyond these specific groups of patients, being wider and more general. It is foreseen in fact that such devices, if the price will be in a reasonable range, will have a wide market also among people without particular coagulation problems, in particular in all the cases in which a fast haemostasis in superficial brushes can be important, e.g. in children, in elderly population or, for the portable device, as a part of first aid kits for example in sports facilities. In the following, a realistic market perspective will be provided, describing the reference market segments for the new devices and highlighting the customer needs and the key success factors that could ensure a good market penetration of these devices once ready for commercialisation.
Topical haemostats market
Sales in topical absorbable haemostats as fibrin sealants, collagen sheets coated with a mixture of fibrinogen and thrombin, and thrombin products are forecast to increase by 7 % CAGR to reach a value of about EUR 850 million by 2011 and are expected to grow to over EUR 1 billion in the next five years. This growth will be fuelled by increased incidence of surgery, greater adoption of these products within the European surgical environment, and the need for improved haemostasis products during minimally invasive surgical procedures. As far as European market is concerned, according to a recent analysis reported in 'European Tissue Sealants and Topical Haemostats Market', it is estimated to reach a value of about EUR 650 million in 2014.
Industry leaders in this sector are at the moment large multinational companies as Ethicon, with 25 % share, King Pharmaceuticals, 3M, or Convatec. Usually SMEs are involved in such market only as manufacturers of single components, without being protagonists and taking advantages of such large market.
Light-based medical devices market
The world market for energy-based devices was well in excess of USD 25 billion in 2008. This represents almost 14 % of the total medical device market; however, the share varies from country to country, since ablation therapy is high technology and fairly high cost; in poorer economies, low-cost medical products such as consumables account for a relatively higher share of the medical market.
Analyses of the medical market by product category typically divide it into a small number of broad product classes such as electromedical equipment, syringes, needles and catheters, and medical consumables; etc. The products included in 'energy-based therapies' are divided among several of these categories.
Light-based devices, which are of interest to understand the market potential of the LIGHT+TER device, are part of energy-based devices. According to LED Magazine, the number of worldwide consumers utilising light-based medical devices will increase to more than EUR 12 million, with consumer sales exceeding 1 billion by 2011. It is worth noticing that in this estimation, laser systems accounts for the large majority of devices and LED technology represents at the moment only a small portion of such large market.
Laser-based devices found their main use in small ambulatory surgery applications, mainly in ophthalmology, dental surgery and dermoplastics. Medical applications of lasers include laser eye surgery and cosmetic procedures such as port wine stain treatment and tattoo removal. The earliest uses in medicine involved the cutting and vaporising of superficial tissues with a far infrared carbon dioxide (CO2) laser; other lasers with different wavelengths, in particular the mid-infrared Nd:YAG laser and ultraviolet excimer laser, that allows deeper tissue penetration, are widely used for dermatological and optic surgery. Over 2 million individuals seek the therapeutic benefits of laser vision correction each year; low level 'cold' lasers are being employed to treat chronic pain relief for debilitating conditions like carpal tunnel syndrome, while intense pulsed light (IPL) that affects subtle changes in collagen is being used to treat vascular and pigmentation irregularities. Furthermore, lasers provide surgeons with more precise cutting tools than the conventional scalpel and can also reducing bleeding occluding small blood vessels along incisions.
According to a BCC Research report , the global market for medical lasers by end use was worth approximately USD 2.7 billion in 2008. This market declined to less than USD 2.3 billion in 2009 under the impact of the recession in many of the world's major economies, it is projected to grow to nearly $4.8 billion between 2009 and 2014, at a CAGR of 16.1 % over the 5-year period. Therapeutic laser applications market was nearly USD 1.9 billion in 2009 and it is projected to reach USD 3.7 billion in 2014, for a 5-year CAGR of 13.3 %.
First aid kits market
First aid kits market is projected to reach USD 79.1 million by 2012. Active lifestyles among young and old alike, meanwhile, are giving year-round life to the first aid category. The trend towards self-care is a major force for widening market opportunities in the first aid products category. The global first aid kits market, part of first aid accessories segment, has been witnessing product advancements coupled with most innovative presentations. According to BizAcumen, Inc., demand has been on rise especially for first aid kits designed to meet the needs of families and sporting industry. Despite the existence of numerous first aid branded products from major players, private labels have been successful in making room in consumer product realm. Additionally, innovation coupled with broad spectrum of products, have been aiding private labels to compete with major players' branded products. United States, Europe and Japan represent the three major markets accounting for an estimated 79 % of the world first aid kits market, as stated by Global Industry Analysts, Inc. Market for first aid kits in Europe has reached USD 22 million in 2010. France, Germany, and the United Kingdom (UK) collectively account for about 70 % of the market. Rapidly industrialising countries in the Pacific Rim such as South Korea, Thailand, India, China, Malaysia and Taiwan are projected to offer better growth prospects. This is attributed to greater unmet resident health care needs along with the effect of healthy economic advances, and the public commitments to boost health-related standards.
Global first aid kits market comprises numerous small-specialised operators and a few large players. Key players include 3M, Acme United Corporation, Beiersdorf AG, Certified Safety Manufacturing, Fieldtex, First Aid Only Inc, HARTMANN Group, and Johnson and Johnson among others.
Customer needs and key success factors
As highlighted in the three previous sections, there are good market perspectives for both local haemostatic products, also in first aid kits and in laser based medical devices. However, in order to evaluate the real market potential of the LIGHT+TER device, it is worth investigating the real point of view of potential customers representative of the market segments addressed by the project, understanding their needs and expectations from a new device for self medication or for ambulatory surgery.
To do this, we have identified two possible customer profiles which well represent the possible end users of the two versions of the LIGHT+TER device:
(a) young women or men with children for the portable device;
(b) dentists for the tabletop device.
For these two customer profiles, we constructed an empathy map, which evidences the aspirations, needs feelings and potential problems to be solved for a specific customer, representative of a whole customer segment. Empathy Map was developed by visual thinking company XPLANE and helps to better understand the customer environment, behaviour, concerns, and aspirations, allowing to identify the strong points of the offer and more convenient ways to reach customers. Ultimately it allows you to better understand what a customer is truly willing to pay for.
To construct the empathy map, we answered to a series of questions on the specific customer profile, also asking directly to people of these categories if necessary. Below are the results for the two types of customers.
According to the above table, it is possible to identify the main market drivers that would lead to the use of new products for haemostasis and fast small traumatic wound healing, both in daily life and in a surgical and medical context, also by people without particular coagulation problems. To address the needs of women with children for example, important characteristics of a new device for superficial wound care would be:
(a) the ease of use;
(b) the improved healing time;
(c) the reduction of scars;
(d) the compactness;
(e) the competitive price with respect to existing products.
The LIGHT+TER portable device will have all the required characteristics, being user-friendly, with a very simple user interface, inducing haemostasis in less than 30 seconds without damaging the surrounding tissues, and hence minimising the presence of scars. Although the price will be higher than standard haemostatic patches or dressings, it will be however competitive, as the device can be reused many times, just changing the biodegradable plaster, sent separately at a very small price. Furthermore, the price foreseen is comparable with that of other electronic biomedical devices commercialised as over the counter products, as for example IR thermometers, that are often used for children. Another key success factor for the portable device, apart from its technical characteristics (as selectivity and reduced healing time), could be the growing environmental consciousness among European population, who may prefer to buy a single device instead of disposable products, if the performances are the same or even better.
The characteristic of the LIGHT+TER portable device makes it also extremely interesting to be included in first aid kits, in schools, fitness centres, grounds or soccer fields, providing an added value service for the large community. This also represents an important potential market for the device, addressing the needs of young women with children for example. As for the market drivers for the optical fibre device, the following aspects appeared to be important criteria for the use of a new haemostatic device or product in surgery:
(a) to prevent excessive bleeding, to ensure safe procedure, and to avoid complications associated with excessive bleeding;
(b) to reduce morbidity thanks to improved procedure, reduced surgery time, and prevention of complications;
(c) to be cost effective and time saving for the medical personnel;
(d) to have aesthetic and perceived benefits for the patient.
The LIGHT+TER optical fibre device satisfies all these requirements, inducing effective haemostasis in small blood vessels, with size up to around 100 - 200 µm, in a very short time, thus reducing the surgery time and minimising complications due to excessive bleeding occurring in small superficial blood vessels. In addition, it minimise the use of suture products having also an aesthetic benefit for the patient, in particular in dermatologic surgery.
In the specific case of dentists, the availability of a tool able to stop bleeding in small blood vessel through a very small probe will be extremely useful, taking into account the reduced space available in oral surgery. The fast haemostasis induced by the LIGHT+TER device will also lead to an important saving of time for dentists, representing another point of strength for the product. In addition, in case of dental surgery, the patients will not have to stop their therapy with anticoagulants, thus preventing even more serious cardiovascular problems. These aspects represent key success factor for the LIGHT+TER optical fibre devices that are even more strengthened by the price aspects: the foreseen cost of the device in fact is extremely low with respect to other similar equipment present in ambulatories for dental treatments or day surgery.
All the above analysis showed that the LIGHT+TER device, in its two versions, has a big potential market also excluding people with coagulation problems due to hereditary diseases or other pathologies. The key success factor will be not only the reasonable expected cost, but also its technical characteristics, able to address the main needs of a large spectrum of potential customers.
Exploitation and dissemination
The technological core of the LIGHT+TER devices in the two versions is the same and it is composed by a LED source with the related optical system, the electronics managing the user interface and controlling the device operation, a power supply and a series of external parts, including case, buttons, etc. Then the over-the-counter device has also a biodegradable plaster to be used as an interface with the wound during the treatment, while the optical fibre device is equipped with an optical fibre and a proper connector.
Preliminary activities beyond the project duration
In order to be able to put the LIGHT+TER devices on the market, a series of activities are required at the end of the project, to ensure their compliance with exiting standards and regulations for medical devices at national and European level.
First of all, in vivo tests will be carried out in the framework of the procedure to obtain the CE marking, in order to validate the clinical efficacy of the device both on healthy patients and in patients with coagulation diseases. The medical structure in which these tests will be carried out will be already selected at the end of the project, and will be indicated in D6.2 to be issued at M24. These tests will be carried out during the clinical trial, after the end of this project, in order to obtain the clinical data able to validate the effectiveness of the device with in vivo data. They will focus on the photocoagulation of superficial abrasions of healthy people under the supervision of a dermatologist; the application of the device on people suffering from coagulation disorders will be also done, under the supervision of a haematologist.
These kind of tests were not foreseen in the project workplan due to the short time frame available and characteristics of this funding scheme (research for SMEs), but need to be carried out as a very first step toward the commercialisation of both devices. Then, having the final device available and tested, the procedure to obtain the CE certification will be completed and, once certified, the marketing of the device could start.
Approach to market
Although the project coordinator L4T owns the patent which is at the basis of the project idea, an agreement has been reached between the prime proposer and the other SMEs in the consortium to license to them the manufacturing and exploitation of the sub-systems and consumables. In particular:
- Light4Tech will be responsible for the assembly LED array with the related optical system (including optical fibre) and heat sink, starting from commercial LEDs and fibres, and to the integration of the overall system.
- MACROS will realise the control electronics for the LED array and the user interface electronics for the two layouts.
- LEPOLAM will supply the power management system and will produce the components for the final assembly of the device (case, buttons..).
- BS will produce the biodegradable plasters for the portable device.
As anticipated, the initial demand is expected to be satisfied by the SMEs in the project consortium and the device will be produced starting from the components supplied by them, and put on the market by L4T.
However, the expected growth in the demand and their geographical dispersion will be far beyond their joint capability to satisfy it. Thus, it is expected that the LIGHT+TER concept and related technologies will be transferred to a wider industrial community, by selling licenses to companies in the medical device sector, who will commercialise the whole system, and to companies operating in each technological sub-sector who will be suppliers of components, generating royalty revenues.
Distributors will be selected for the different Countries, with whom special agreements will be stipulated in order to define the economical and Intellectual properties conditions.
Description of the supply chain
The supply chain for the LIGHT+TER devices is formed by the producers / integrators of the single components which constitutes the device.
In the first stages after the commercialisation of the system, the companies involved in the project activities and in the development of the device will be the main suppliers of components and thus the main players in the supply chain. In particular:
- Light4Tech will be responsible for the assembly LED array with the related optical system (including optical fibre) and heat sink, starting from commercial LEDs and fibres, and to the integration of the overall system.
- MACROS will realise the control electronics for the LED array and the user interface electronics for the two layouts.
- LEPOLAM will supply the power management system and will produce the components for the final assembly of the device (case, buttons.).
- BS will produce the biodegradable plasters for the portable device.
As anticipated, the initial demand is expected to be satisfied by the SMEs in the project consortium and the device will be produced starting from the components supplied by them, and put on the market by L4T. However, the expected growth in the demand and their geographical dispersion will be far beyond their joint capability to satisfy it. Thus, it is expected that the LIGHT+TER concept and related technologies will be transferred to a wider industrial community, by selling licenses to companies in the medical device sector, who will commercialise the whole system, and to companies operating in each technological sub-sectors who will be suppliers of components, generating royalty revenues.
Distributors will be selected for the different countries, with whom special agreements will be stipulated in order to define the economical and Intellectual properties conditions. Industry cost structure.
Having described the supply chain for the final production of the LIGHT+TER devices, it is possible to estimate their final selling price, taking into consideration the estimated production costs for each subcomponent, and other expenses that will be sustained by the companies involved in the commercialisation, as for example costs for the CE mark procedure, costs for clinical evaluation etc.
The estimation of the final price of the LIGHT+TER device allows to better understand the competitiveness of the product on the market as well as its sells potential. Furthermore, together with the analysis of the market trends, it can help to identify which one of the two layouts will be more promising in terms of market potential. Table 3 below reports a realistic forecast of the initial costs for the components required to assembly the two versions of the LIGHT+TER LED device. The two values indicated refer to a prototype production (higher value) and to a volume production of 100 000 units.
The costs presented refer to the core of the LIGHT+TER device, without optical fibre, and have been estimated taking into account that increasing the production volume, the cost of the components will be drastically reduced, even in case of the LED module, which is the most expensive part of the device.
According to these data, the cost of the LIGHT+TER device in the over the counter version will be about EUR 215 in the prototype phase, but will be reduced down to EUR 35 in case of a production of 100 000 units, leading to a selling price of about EUR 50 - 60. This price is actually higher than haemostatic patches and common dressing, but it can be affordable taking into account the many advantages with respect to existing products, as for example the fact that it is reusable.
As for the optical fibre device, the component cost will be similar to that of the portable device: only a slightly higher cost can be foreseen for the user interface electronics, but the incidence on the final price will be very small. In addition, the cost for the optical fibre bundle and the connector must be added, which can be estimated in about EUR 100 for small volumes, to be reduced to EUR 40 for large supply volumes. In this framework, as a realistic forecast one can estimate that the optical fibre device will be put on the market with a price of about EUR 200 - 250, extremely low with respect to other instruments used in dental ambulatories or during day surgery.
The estimated selling price for the two devices has been calculated adding 30 % to the estimated components costs to account for investments for marketing, promotional campaign, costs for assembly and packaging, and for obtaining CE mark and certifications. Taking into account these values and the potential end users, it can be estimated that after a promotional campaign, within 5 years from the end of the project, leading to about 500 000 pieces sold, the revenue for the LIGHT+TER portable device could be projected to be about EUR 25 million. This estimation can be even larger for the system with the optical fibre, where the end users are dentists, first aid organisations, hospitals, ambulatories and centres for day surgery.
Distribution channels
Taking into account the large market potential emerged from the present analysis, the SMEs in the consortium agrees on the need to transfer the LIGHT+TER concept and related technologies to a wider industrial community by offering licenses all over Europe and generating royalty revenues. Preliminary discussions are being carried out under non-disclosure agreements with other European companies involved in medical device production and distribution which thus would contribute to LIGHT+TER penetration. Licenses negotiations will be carried out as soon as the market demands will be generated, which is expected to be after the fifth year since LIGHT+TER commercialisation.
During the commercialisation phase, three business routes will be followed, in order to ensure an effective take up from the market of wound care, haemostatic products and laser medical devices:
- The direct selling of the LIGHT+TER device to the end users, to be carried out in the first promotional phase, when production volumes will be small.
- Sale of the single components to companies interested to assembly the final device, upon opportune licensing of the whole LIGHT+TER concept: this strategy would be interesting in order to penetrate in the market in a more effective way, exploiting the visibility of larger medical companies.
- Licensing of the concept of single components to other companies in the medical device sector on a case by case basis: this route will be effective when production volumes will increase as a consequence of a growing market demand and large companies will have larger production facilities.
As for the distribution channels to the end users, there will be two main routes to reach a the community of end users, taking into account the product characteristics. The portable device, as already discussed, has been conceived as an over the counter product, and thus it will be sold in pharmacies or shops specialised in sanitary and medical products. In this case, the company in charge for device assembly will be responsible for distributing the product, unless the distribution will be carried out by other distribution companies selected for each country.
The optical fibre device instead, being used mainly in hospitals, ambulatories, dentists, will be put in commerce directly by the company in charge of the assembly, who will interact directly with end-users through sales representatives.
List of websites: http://www.lightplaster.com(odnośnik otworzy się w nowym oknie)
LIGHT+TER project aims to develop a new range of low-cost and easy-to-use medical devices able to induce coagulation in superficial wounds, in all the cases where a rapid and effective haemostasis is required. The project thus addresses both a public health problem, i.e. coagulation disorders, typical of hereditary diseases like haemophilia (40 000 people affected in the European Union (EU)-27), or induced by use of specific anti-coagulant drugs (20 million people in EU-27) and the needs of a wide category of people as children or elderly population for whom even small superficial brushes may need a fast intervention. Bleeding problems in general have a strong impact on the quality of life. Even small medical interventions, as dental surgery for example, pose important problems for these patients, requiring the suspension of the anticoagulant therapy days before the surgery, with the consequent risk of having a relapse of the cardiovascular problem. In this framework, there is a technological need for a cheap, safe and easy to handle tool to help blood coagulation, to be used directly by the patient or by low-specialised personnel. Starting from this social need, the emerging optoelectronics technologies can offer a possible solution, as the use of miniaturised and non-invasive devices based on optoelectronics that exploit the properties of light to bring about certain effects is becoming more and more diffuse, especially for micro-surgery, dermatologic treatments, ophthalmology and plastic surgery.
The final goal of LIGHT+TER project was to address this need through the development of a compact and easy to use medical device based on light-emitting diode (LED) technology, able to induce haemostasis of skin blood vessels without damaging the surrounding tissues. The main mechanism at the basis of LIGHT+TER project is photo-thermo haemostasis (conversion of radiant energy to heat by haemoglobin that results in thermal denaturation of blood) which up to date has been realised only through very expensive, bulky and complex laser sources. LIGHT+TER project, starting from the concept at the basis of a patent owned by the small and medium-sized enterprise (SME) partner Light4Tech, aims at demonstrating the use of low cost LEDs to induce non-invasive photo-thermal coagulation, and developed two prototypes of medical device that could be configured both as an over-the-counter product and as an ambulatory tool (e.g. dental surgery).
These two prototypes are the basis for two commercial products to be optimised in the future, providing a good opportunity for the 34 500 SMEs active in EU in the biomedical sector to gain market share in medical device market with an innovative range of products with important commercial perspectives.
Although the original target end users for the LIGHT+TER devices were people with coagulation diseases, the consortium evaluated also other customer segments in order to show that the market perspectives for the device go beyond these specific groups of patients.
From the economical point of view, by developing a LED-based medical device for the haemostasis of superficial capillary vessels, LIGHT+TER addresses two sub-sectors of the medical device market:
- Wound care device market, including products like mechanical staples or sutures for wound closure, dressings or bandages for wound care, surgical sealants, adhesives and topical absorbable haemostats.
- Laser-based medical device market, mainly used in microsurgery, ophthalmology, dental applications and dermoplastics.
Aiming at a market penetration of 2 % after 5 years after the project completion, with a potential market of about EUR 200 million.
Project context and objectives:
The main goal of the LIGHT+TER project is to develop a innovative medical device based on LED technology for non-invasive haemostasis to benefit specific categories of people as children or elder population or people suffering from coagulation problems, for whom even small superficial brushes may need a fast intervention.
A large number of coagulation disorders that makes the haemostasis process difficult, impact negatively on the quality of life and require attention in normal daily living. Even superficial wounds in the first layers of the skin may become a problem for specific groups of people, due to the difficulty in coagulation. People with heamostasis problems may incur in severe bleeding even after a small abrasion and they need to fall into specific procedures when they have to undertake a minor surgery, as for example a dental surgery, dermatologic treatments or ambulatory therapies. Among people with coagulation problems, together with people with specific hereditary diseases, are the 20 million people in Europe who assume anticoagulants that, making blood more fluid, can also cause problems in haemostasis process.
In order to avoid the difficulties described above, there is the technological need for a cheap, safe and easy-to-use device to speed up blood coagulation that can be used directly by the patient or by low-specialised medical personnel.
To better understand how the device developed within the LIGHT+TER project works, it is worth examining the heamostasis process.
The haemostasis of blood vessels can be achieved by three main methodologies, local mechanical compression, pharmacological treatment, or thermal coagulation.
Electrocoagulation and photocoagulation, both thermal coagulation techniques, can be used in order to transfer heat to the wound blood vessels. Electrocoagulation is used in surgical applications to treat haemorrhage, like bleeding ulcers, and to ablate tumours, mucosal lesions and even refractory arrhythmias. The major disadvantage in the use of this technique is that it is not selective: the heating induced by the electrical current in fact involves also the surrounding tissues close to the vessels, producing as a side effect the presence of unsightly burns on the treated skin. Moreover, the needed instrumentation is difficult to be transferred to out-of-hospital applications, and the risks connected to its use make it impossible to be used in self-medication.
The photocoagulation technique consists in the light radiation of the tissue. At the state of the art, laser is the most common light source used in biomedical devices. In recent decades the use of medical devices based on laser as for example in dermatologic laser surgery has dramatically increased. When radiation hits the skin, it may be reflected, transmitted, or absorbed. Absorbed energy is mostly responsible for the clinical effect due its thermal energy conversion through absorption of several skin components, like blood, water and melanin. The use of extremely high power and concentrated radiation, as in the case of laser used as photocoagulator, the treatment induces collateral damage because typically the light is not selectively absorbed by a single chromophore, but heats also the surrounding tissue and creating collateral effects as hyperpigmentation and hypopigmentation. In order to reduce undesired collateral damages induced by use of laser, the selective photothermolysis based on Anderson and Parrish's theory has been recently introduced.
This theory states that selective heating of a target chromophore is achieved when the laser wavelength is preferentially absorbed by the chromophore, the energy of the laser is high enough to damage the chromophore, but the pulse duration of laser energy is shorter than the thermal relaxation of the target. The majority of cutaneous treatment based on lasers in use today operate according to these principles and attempt to limit the duration of the laser light that reach the tissue. The use of laser light with the property to be selectively absorbed only by haemoglobin has the disadvantage to be very expensive and frequent maintenance interventions are need.
To overcome all the technological limitations of the photocoagulation devices based on lasers, the development of a new cheap, compact and easy-to-use photocoagulation device based on the emerging optoelectronics technologies, as high power LED sources, able to induce haemostasis of skin blood vessels through a selective photo-thermo-coagulation process is thus highly desirable.
The mechanism at the basis of LIGHT+TER project is photo-thermal haemostasis, that is the conversion of light energy into heat due to selective absorption by (de)oxyhaemoglobin and subsequent heat diffusion in order to obtain thermal denaturation of blood and vascular tissue. The appropriate selection of the LED light wavelength that ensures the selectivity of the process, in particular the specific absorption wavelength of the light by haematic components, as haemoglobin, ensures that the light interacts only with the blood components and not with the surrounding tissues guaranteeing the minimum invasivity of the technique. The technique is based on a patent 'LED device for blood vessel haemostasis', owned by SME partner Light4Tech, in which the novel concept of photocoagulation is demonstrated using incoherent ultraviolet (UV) radiation. Using light with wavelength in the range 400 - 450 nm, radiation power between 0.5 and 1 W and an exposure time of about 1 minute is possible induce photocoagulation on bleeding superficial wound, as demonstrated through an extensive testing by Light4Tech in cooperation with LENS and CNR, using large and cumbersome laboratory light source equipment projecting UV radiation on animal wounds. In particular the testing performed by Light4Tech demonstrated that the wound exposed to the light heals faster than a wound unexposed.
There are consistent advantages using LEDs instead of lasers, in particular the LED sources are more compact, allowing for the possibility to develop a portable device, have low energy consumption enabling the use of batteries and, last but not the least, they are definitely cheaper than laser sources allowing for the development of an over-the-counter product. The use of LED source is also safer than the laser source both for the patient and operator, and the recent advancements in LED technology, in particular the increase of the optical emitted power up to 1 Watt, in the close ultraviolet (390 - 470 nm), where haemoglobin has the maximum optical absorption peak, allow the technical feasibility of the intended device. The LIGHT+TER project aimed to further develop the patented concept by Light4Tech, thus demonstrating the use of low cost LED source to induce photo-thermal haemostasis, in two possible layouts.
In the layout no 1, the photocoagulator will have the appearance of small torch, in order to be easily manageable and will be powered through a rechargeable battery, ensuring the portability of the system, for example in first-aid applications. The portable device is identified as 'self-medication' device to be sold as an over-the-count product, and will be used in conjunction with a biodegradable polymeric plaster transparent to UV-blue light, that will serve as interface between the wounded skin and the LED light source, in order to avoid any type of bacterial contamination.
The layout no 2 consists in an ambulatory version of the device, in which the optical fibre is used to transmit the LED radiation, in order to be used by specialised personnel for ophthalmologic, dental, micro-surgery and plastic surgery applications.
The devices are composed by the following components:
(a) LED-based source, based on LED source with emission in the close UV region, with total power in the range 0.5 - 1 W, enough to induce haemostasis;
(b) the electronics, for the management of the LED source in order to control the emitted optical power, for the switch on / off operations, for control of user interface display and power supply;
(c) the optical system, able to focus the LED light on the skin in the case of layout no 1, and in an optical fibre in the layout no 2.
Regarding the practical use of the LIGHT+TER device, the portable device (layout no 1) is intended to be adopted in first-aid situations, in order to stop the superficial abrasions bleeding and its use consist in the application of the LED light directly onto the skin where bleeding occurs.
To ensure a sterile interface between the wound and the portable device, a specific plaster, made of a biocompatible and biodegradable material transparent to the LED wavelength has been developed. The optical fibre device (layout no 2), is intended to be used in hospital environments by specialised personnel for ambulatory applications.
However in order to bring this concept into a working hand-held able system, the following objectives had to be achieved:
(a) replacement of the UV lamp with compact and cheap LED source;
(b) design and development of focusing optical system that is also able to focus LED light into an optical fibre;
(c) design and implementation of a compact and miniaturised control electronics and power supply for the devices;
(d) identification of a polymeric material for the biodegradable plaster, transparent to the UV-blue light;
(e) set-up of a model of the interaction between light and polymeric material of the plaster in order to provide the LED light propagation into the different structures of the skin.
Beyond the project, major goal of the partners will be of course to achieve a CE mark for the final product, conducting the required clinical validation. Commercial versions of the devices are expected to be ready within 12 - 18 months from the end of LIGHT+TER project in order to be inserted in the biomedical market.
Project results:
During the duration of LIGHT+TER project, started on 1 January 2010 and finished on 31 December 2011, the activities have generated the following results:
(a) application of LED technology to induce haemostasis;
(b) control electronics;
(c) disposable plaster;
(d) optical setup for micro-surgical applications;
(e) LIGHT+TER device integration.
In the following, the above mentioned results and the activities performed to achieve them will be described in detail.
Application of LED technology to haemostasis
After the identification of the technical requirements of the LIGHT+TER devices taking into account all optic, physic and electronic aspects, three parallel but strongly interconnected research lines were started, one dedicated the LED-based source and optical system definition and design, one dedicated to the control and User-interface electronics and another one on the biodegradable plaster.
During the activities of design and development of the LED-based optical system, the consortium has developed the light-tissue interaction model, defined and tested the LED source and developed the optical system for the portable device.
Concerning the light-tissue interaction, a model based on the finite element method (FEM) has been developed and used to fix and verify the parameters required to induce haemostasis through the photothermal effect. After the theoretical treatment on the light-tissue interaction, human skin physics and optical properties, we have moved to a discussion on mathematical models. In particular, various mathematical models have been developed to study light / tissue interactions and to predict optimal light source parameters to achieve high-efficacy light-based treatment or diagnostics procedures. In all of these models, the biological tissue and in particular the skin, is considered as an optically turbid medium. The best solution for analysing through a model the light-tissue interaction is the use of the FEM, with which is possible to solve contemporarily more than one partial differential equations, studying the solution in space and time. This goal may be achieved with commercial software developed to solve multiphysics problems. Among the software that are commercially available, only the Comsol Multiphysics (produced by Comsol AB, Stockholm, Sweden) had the characteristics that enabled a user-friendly approach to this complex problem, and it was chosen to describe this particular light tissue interaction both in space and time. Moreover, the reliability of this FEM analysis of photothermal processes has been already proved by previous studies that combined the predictive analysis with experimental measurement of the temperature and histological and morphological analysis of the treated tissues. Aim of the modelling study of light / tissue interaction, is to indicate a light wavelength region were light absorption is localised in the blood content of the tissue and predominantly converted into a heat effect. The induced temperature and treatment time has to be optimised in order to induce coagulation in the blood fraction of the tissue, while the healthy tissue has not to be affected by irreversible thermal damage. Moreover, different irradiation conditions have to be tested, in order to indicate the best conditions to be designed. The modelling study of light / skin interactions evidenced that blue light sources may be used to induce a selective photothermal effect in the skin. The proposed approach is a possible solution for coagulation of superficial bleeding, as it induces a localised effect in the blood region in question without having any significant collateral effects on the surrounding tissues. The selective photo-thermal coagulation may be induced with the light source in close contact with the tissue. From this theoretical study, it has been pointed out that we could induce high temperatures inside the tissue, able to induce photocoagulation of superficial capillaries without inducing irreversible damages to adjacent tissue. The best wavelength to be used is in the range 400 - 450 nm. The best treatment time using a LED source with central wavelength at 405 nm with 300 mW of power output is 30 s, by keeping the LED surface in close contact with the tissue. The active area considered is 8 mm in diameter. In this conditions, a photocoagulator may be designed.
Concerning the LED-based source, once the main parameters derived from the light-tissue interaction have been obtained, it was possible to define a list of sources that could be taken into account for the device development. The LED sources that best fit the required performances for the LIGHT+TER device are produced by the company Roithner LaserTechnik (RLT) (see http://www.roithnerlaser.com/(odnośnik otworzy się w nowym oknie) online for further details) from Vienna, Austria. The best LEDs for our scope are models LED405-66-60 and LED435-66-60. The model LED405-66-60 emits 300 mW of optical power at 405 nm emission peak, while LED435-66-60 emits 720 mW of optical power at 435 nm emission peak. High power LED source with emission peak at 415 nm is also available, but it does not provide enough optical power to induce haemostasis (the minimum required power is 300 mW, as derived from the light-skin interaction model). Both LED sources were tested to check the optical properties of optical power emitted that the wavelength spectrum. The tests have confirmed that the LED sources identified are the best source for the self-medication layout in term of wavelength and optical power. As regards the LED-based source for the optical fibre layout, the LED source that best fit the required performances is the model Luxeon Rebel Royal Blue star (LXML-PR01-0500) produced by the company Lumileds, which emits 875 mW of optical power at 447.5 nm emission peak. Each LED source indicated above was coupled and tested with an optical system for managing the angular divergence of the incoherent light of the LED. In particular for the LED by RLT, for the portable device, has been tested in combination with optical system model TO-18, which named LED aspheric glass lens, with a diameter of 18 mm and focal distance of 13.5 mm, while for Rebel LED was used the model Carclo LED fibre coupling with focal distance of 20 mm.
Control electronics
The aim of the control electronics activities was to design and develop the miniaturised electronic board for the control and management of the LED source, providing the correct power supply and setting of the optical power emitted, together with the development of the electronics for the user interface. For the portable device, battery powered, a step-up current feedback converter is required, because the LED module operates at 18 V, driving 250 mA. It is very difficult to obtain such voltage directly from commonly available rechargeable batteries. After some battery endurance tests the chosen battery configuration is 4 x 1.2 V AA rechargeable Ni-MH batteries. The device could continuously operate for 2-3 hours from 2 400 mAh batteries AA type. Using smaller footprint AAA batteries (1 000 - 1 200 mAh typically) the device could operate continuously for about 1 hour. Typical light burst is estimated at 20 second length, about 500 applications before of complete discharge of the AA batteries, while with type AAA batteries is possible to reach 200 applications with a charge cycle.
The power converter is based on MC34063 chip, a simple and reliable boost converter, with about 80 % conversion efficiency and current feedback. The power converter footprint is only 3 x 2cm on the printed circuit board. This step-up power converter design ensures constant 250 mA current flowing through LED module, even if its voltage drop changes e.g. by temperature change. It is controlled by single ENABLE signal, connected to the microchip controlling the user interface for easy switch. The first version of the user interface has been designed according to the specifications fixed by technical requirements report. It is composed from two 7 segment display for elapsed time, 2 colour red/green LED diode for battery status and two pushbuttons: TIME and START. Pushing the TIME button adds 10 seconds to the timer and START enables the lighter and triggers the countdown. After 10 seconds of inactivity, either after finishing countdown or just not triggering START, the device returns to power down mode, in order to avoid the discharge battery. Battery status is shown using two-colour LED, changing its colour from green, thought yellow, to red. Thanks to the flexible microcontroller design it is possible to program any other user interface mode. With such user interface, the whole electronic could be assembled on a small circuit board measuring about 3 x 5 cm (with batteries in the external case). Prototype built on designed printed circuit board (PCB) using surface-mount device (SMD) technology could be much smaller and fit to any design of the plastic cover.
For the optical fibre layout, through microcontroller programme, the button functions have been reconfigured to serve START and STOP functions. After pressing START button the display shows elapsed time since start event. Switching from portable layout mode to optical fibre layout mode is a matter of loading different firmware to the microcontroller. In the final product firmware will be protected. For the development of the prototype, the microcontroller Attiny26, a low cost AVR core microcontroller manufactured by Atmel, has been chosen.
Concerning the miniaturised and final version of control electronic, in order to reduce and optimise the spatial dimension of the electronic PCBs, we have chosen to design two modules, the main module, named L+T-M, with microcontroller and LED diode driver, and the display module, named L+T-D, with 3-digit display. The main module L+T-M is common to the two versions of the device, which differ only for the components soldered, while the display module, named L+T-D, will be present only in the optical fibre device. Two versions of the L+T-M module and one version of the L+T-D module have been realised.
The portable version of the LIGHT+TER device comprises only the main module L+T-M, with the electronic component able to manage the power supply by batteries compartment. In this version the connector BAT is used to plug the battery power supply, while the power LED module driver is based on the integrated circuit MC34063ABD that is the core of step-up converter. Its operation is controlled with the ENABLE signal, which in high state turns on the driver, and in low state turns it off. The second integrated circuit, microcontroller ATtiny26IA-SU, apart from controlling the driver, monitors the battery supply voltage, reads the state of the pushbutton and controls up to two LED diodes operating as indicators. The pushbutton and these diodes are connected to the J1 connector, which is also used for programming the microcontroller in case it is needed to change the configuration of the device. The bill of materials of the L+T-M module for the portable device has been done together with an assessment of the production costs of the PCB for the portable device.
The optical fibre version of the LIGHT+TER device comprises a L+T-M module, with the electronic component able to manage the power supply by + 5 V direct current (DC) power supply, and a L+T-D module. The module L+T-M is equipped with connector PSU, which gets the power from external 5V power supply unit. Diodes D2, D3 and transistor Q2 form a supply switching circuit, which selects the external power supply, when present, or the batteries otherwise. Voltage from the PSU connector is also passed directly to microcontroller ATtiny26IA-SU, so that it can determine whether it is running on the external supply or batteries. In this version, the microcontroller ATtiny26IA-SU manages the display on the L+T-D module as well. The connection between the two modules is provided by a 10-wire, pitch 1.27 mm ribbon cable, from header J2 on L+T-M module to J1 on L+TD. Module L+T-D comprises a BCD to 7-segment display decoder and a triple 7 segment display. The microcontroller sets a logic level in order to set the number 0-9 on 3-digit display. Quickly sweeping through all three positions of the display, the microcontroller can make a three digit number visible. The bill of materials of the L+T-M and L+T-D modules for the optical fibre device was prepared and the production costs of the PCBs were assessed.
Disposable plaster
After a careful examination on the state of the art on biodegradable polymers, the consortium has developed a light-polymer interaction model, based on FEM, verifying the interaction of the biodegradable polymers with the blue light in order to select the material satisfying the requirements, also in terms of biodegradability, flexibility and transparency to UV-blue light. Was also studied the dependence of the transparency to UV-blue light as a function of film thickness used as interface between the device and bleeding wound. The choice fell on polylactic acid (PLA) and the study on the extrusion process of PLA films has been carried out, taking into account the physical and mechanical characteristics of the material. A biodegradable plaster prototypes based on PLA has also been realised. The biodegradable plaster must ensure a safe interface between the injured skin and the portable LIGHT+TER device during application. The prototype are based on the PLA film, which is transparent to the wavelengths required for haemostasis, and are surrounded by an adhesive part similar to a standards patch to ensure a good contact with the skin. It is worth noting that the plaster has to remain in contact with the skin only for the time of application required for haemostasis which is below one minute: for this reason, it is not necessary to have a very strong adhesive. Two sizes have been chosen (10 x 8 and 5 x 7 cm), to facilitate the use also in case of larger wounds, without replacing the plaster between two applications of the device on two parts of the wound.
Optical setup for micro-surgical applications
The optical setup for micro-surgical applications comprises the optical fibre connector to the LED source and the choice of the appropriate optical fibre, that can be used in the optical fibre LIGHT+TER device. The choice of the optical fibre has been done taking into account several characteristics. The fibre core material were chosen in plastic for their low cost and the possibility to be disposable. various plastic optical fibres are available on the market, the choice has been made considering the transmission of the fibres in the UV-blue region of the spectrum. Since the fibre diameter affects the angular emission and the maximum optical power available in the irradiated area to induce photo-haemostasis, during the activities plastic optical fibres of various diameters have been tested. The fibre tested are constituted by inner core of polymethyl methacrylate (PMMA) resin and a cladding of Fluorinated polymer, with global fibre diameter of 1 mm, 1.5 mm, 2 mm and 3 mm, and a length of 0.8 m.
In order to perfectly coupling the LED source and the plastic optical fibre, a mechanical mount has been developed, to centre the axis of optical propagation of the two components. The two parts, together with the LED source and the optical fibre, represent the prototype light source for the optical fibre layout. Figure 9 shows the mechanical rail to mount the LED on its heatsink, because the heatsink will represent the mechanical reference to centre the optical fibre respect to LED.
The first mount is constituted by a rail with a fixed part, in blue, and a moving part, in green. The fixed part works as holder for the heatsink of the LED source; the moving part is properly shaped to fit the holes located in the six corners of the hexagonal PCB of the LED source, as depicted in Figure 10. This mount serves to fix the LED source centred and aligned with respect to its heatsink.
It is made with two cylindrical coaxial mechanical mounts. The former mount allows to fix on it the LED source, together with the heatsink, the lens holder and the focusing optics. The latter mount, indicated in gold, works as a holder for the plastic optical fibre and it can be inserted in the former mount allowing proper positioning with respect to the optical system and LED source, maximising the optical coupling.
This optical-fibre connector and relative fibres with different diameter have been tested, in order to check the optical power at fibre output. The plastic optical fibres were all tested with the LED source equipped with focalisation apparatus and the optical fibre placed in the focus of the focalisation apparatus itself. The optical power irradiated at the fibre output was measured, together with the typical angular emission. The LED source was mounted on its mount together with the focalisation apparatus, the dedicated heatsink and supplied with a variable DC current. The current was varied in the range between 50 mA up to 1 000 mA with steps of 50 mA. The plastic optical fibres were placed in the focus of the focalisation apparatus and bent with a radius of curvature of approximately 10 cm. The fibre output was placed in front of a power meter OPHIR model PD300-3W. The emitted power at the fibre output was measured versus the input current flowing in the LED source. The angular emission was evaluated by measuring the angular profile of light emitted at the fibre output.
In order to compare the plastic optical fibres tested and to find the optimal solution for the optical fibre layout, the characteristics of maximum power density and angular emission has been considered.
The results provided by the test has been used as input for the theoretical model of light-tissue interaction, developed for the LIGHT+TER project. The model has been used to verify the photo-haemostatic capability of the optical fibre layout. The theoretical simulations have been done using 447 nm as excitation wavelength, corresponding to the central emission wavelength of the rebel LED source, and an emitted optical power with angular emission corresponding to the data measured for different plastic optical fibres tested. The theoretical simulations have been done considering the optical fibre output located at a distance of 1 mm from the tissue to be irradiated. According to the photohaemostasis model of the light and skin interaction, in all the configuration cases examined, the power density available at the fibre output is enough to perform photo-haemostasis, albeit with different irradiation time. The most comforting result is that for all the optical fibre configurations the temperature at which the denaturation process is triggered is achieved, activating photohaemostasis, although the size of the illuminated area differ. In particular, the fibre with diameter up to 1.5 mm, requires irradiation time beyond 30 seconds to reach temperatures around 70 - 80 degrees of Celsius, while the fibre with 2 mm diameter, after 5 seconds of irradiation already reached the temperature above which it begins to produce damage at the surrounding tissue. The choice of the best fibre configuration depends on the extension of the illuminated area and on the speed of the application required.
LIGHT+TER device integration
The LIGHT+TER devices integration started with the plastic case design and continued with the integration of all the sub-parts to obtain two device prototypes. The portable case device is made of four different parts each designed to be easily connected with each other without the use of screws or additional components. The internal space was optimised to keep the overall dimensions low, having the final dimensions of 140 x 56 x 50 mm (LxWxH), suitable for easy handling and use by different users / patients. The portable case was also designed to have no edges and to avoid getting hurt while it is handled.
Furthermore, the material is also sufficiently resistant to not shatter when the case is dropped. The bottom case part constitutes the main body, where most of the device internal components are mounted to it, the first case component to be mounted is the top case part which connects to the bottom case by snap-in connections. The battery compartment case part has the same connection method as the top case, and joins with both the top and bottom case parts. To disconnect the components from each other, the snap-in connections can be released be pressing on the levers using a thin object such as a screwdriver. The portable case has two distinct compartments in which all the components are firmly mounted. The right area includes the power supply of the portable device, constituting of three AA batteries and electric terminals, while on the left side there is the PCB with all the connections, push button, optical lens, LED source and its heatsink.
The case design of the optical fibre version has different features with respect to the portable case design. However, the design process followed the same targets defined for the portable case where the case had to be lightweight, ergonomic, and safe. Since the tabletop device is based on fibre optics, it has different components compared to the portable device and the final dimensions are 100 x 110 x 80 mm (LxWxH). The tabletop case is made of two main parts: a top part and a bottom part. The two parts connect using snap-in connections which tightly join the two case parts without the need of screws. The front part has visible all the fundamental elements necessary for the user, including the display, to operate the device. The display digit is placed at a 45-degree angle being suitable for reading it when the user is either sitting at the desk or standing up. On the left side of the display there is a coloured LED indicator which has the purpose to notify the user when the system is receiving power and ready to operate. On the other side of the display there is a round push button which starts and stops the operation of the system when pressed. Once this button is released, the display will start counting the operation time elapsed. On the case in the rear side there are the switch to turn ON the device and a power connector, which receives electricity from the socket on the wall. The PCB for the tabletop device was positioned to easily connect the internal components. In the tabletop device, there are two PCBs mounted to the case, the first is the main PCB, being the same for the portable device, and the second PCB was designed to manage the display. The optical fibre connector is mounted to the case without screws. A hole at the front of the case was also added to allow the passage of the optical fibre through the case.
The prototype cases, the LEDs source and the electronic PCBs in its miniaturised version have been integrated to construct the LIGHT+TER devices prototypes.
The tests on the prototypes confirmed that the overall performances of devices are the same of the single subparts.
Potential impact:
Although the main target end users for the LIGHT+TER devices indicated in the Description of Work are people with coagulation diseases, such as haemophilia or other diseases, it is not possible to prove without specific in vivo tests, not foreseen within the project, that some specific clinical conditions occurring in these patients do not interfere with photocoagulation process at the basis of the intended device.
In this framework, it is worth evaluating other possible customer segments, in order to show that the application fields and market perspectives for the LIGHT+TER device go beyond these specific groups of patients, being wider and more general. It is foreseen in fact that such devices, if the price will be in a reasonable range, will have a wide market also among people without particular coagulation problems, in particular in all the cases in which a fast haemostasis in superficial brushes can be important, e.g. in children, in elderly population or, for the portable device, as a part of first aid kits for example in sports facilities. In the following, a realistic market perspective will be provided, describing the reference market segments for the new devices and highlighting the customer needs and the key success factors that could ensure a good market penetration of these devices once ready for commercialisation.
Topical haemostats market
Sales in topical absorbable haemostats as fibrin sealants, collagen sheets coated with a mixture of fibrinogen and thrombin, and thrombin products are forecast to increase by 7 % CAGR to reach a value of about EUR 850 million by 2011 and are expected to grow to over EUR 1 billion in the next five years. This growth will be fuelled by increased incidence of surgery, greater adoption of these products within the European surgical environment, and the need for improved haemostasis products during minimally invasive surgical procedures. As far as European market is concerned, according to a recent analysis reported in 'European Tissue Sealants and Topical Haemostats Market', it is estimated to reach a value of about EUR 650 million in 2014.
Industry leaders in this sector are at the moment large multinational companies as Ethicon, with 25 % share, King Pharmaceuticals, 3M, or Convatec. Usually SMEs are involved in such market only as manufacturers of single components, without being protagonists and taking advantages of such large market.
Light-based medical devices market
The world market for energy-based devices was well in excess of USD 25 billion in 2008. This represents almost 14 % of the total medical device market; however, the share varies from country to country, since ablation therapy is high technology and fairly high cost; in poorer economies, low-cost medical products such as consumables account for a relatively higher share of the medical market.
Analyses of the medical market by product category typically divide it into a small number of broad product classes such as electromedical equipment, syringes, needles and catheters, and medical consumables; etc. The products included in 'energy-based therapies' are divided among several of these categories.
Light-based devices, which are of interest to understand the market potential of the LIGHT+TER device, are part of energy-based devices. According to LED Magazine, the number of worldwide consumers utilising light-based medical devices will increase to more than EUR 12 million, with consumer sales exceeding 1 billion by 2011. It is worth noticing that in this estimation, laser systems accounts for the large majority of devices and LED technology represents at the moment only a small portion of such large market.
Laser-based devices found their main use in small ambulatory surgery applications, mainly in ophthalmology, dental surgery and dermoplastics. Medical applications of lasers include laser eye surgery and cosmetic procedures such as port wine stain treatment and tattoo removal. The earliest uses in medicine involved the cutting and vaporising of superficial tissues with a far infrared carbon dioxide (CO2) laser; other lasers with different wavelengths, in particular the mid-infrared Nd:YAG laser and ultraviolet excimer laser, that allows deeper tissue penetration, are widely used for dermatological and optic surgery. Over 2 million individuals seek the therapeutic benefits of laser vision correction each year; low level 'cold' lasers are being employed to treat chronic pain relief for debilitating conditions like carpal tunnel syndrome, while intense pulsed light (IPL) that affects subtle changes in collagen is being used to treat vascular and pigmentation irregularities. Furthermore, lasers provide surgeons with more precise cutting tools than the conventional scalpel and can also reducing bleeding occluding small blood vessels along incisions.
According to a BCC Research report , the global market for medical lasers by end use was worth approximately USD 2.7 billion in 2008. This market declined to less than USD 2.3 billion in 2009 under the impact of the recession in many of the world's major economies, it is projected to grow to nearly $4.8 billion between 2009 and 2014, at a CAGR of 16.1 % over the 5-year period. Therapeutic laser applications market was nearly USD 1.9 billion in 2009 and it is projected to reach USD 3.7 billion in 2014, for a 5-year CAGR of 13.3 %.
First aid kits market
First aid kits market is projected to reach USD 79.1 million by 2012. Active lifestyles among young and old alike, meanwhile, are giving year-round life to the first aid category. The trend towards self-care is a major force for widening market opportunities in the first aid products category. The global first aid kits market, part of first aid accessories segment, has been witnessing product advancements coupled with most innovative presentations. According to BizAcumen, Inc., demand has been on rise especially for first aid kits designed to meet the needs of families and sporting industry. Despite the existence of numerous first aid branded products from major players, private labels have been successful in making room in consumer product realm. Additionally, innovation coupled with broad spectrum of products, have been aiding private labels to compete with major players' branded products. United States, Europe and Japan represent the three major markets accounting for an estimated 79 % of the world first aid kits market, as stated by Global Industry Analysts, Inc. Market for first aid kits in Europe has reached USD 22 million in 2010. France, Germany, and the United Kingdom (UK) collectively account for about 70 % of the market. Rapidly industrialising countries in the Pacific Rim such as South Korea, Thailand, India, China, Malaysia and Taiwan are projected to offer better growth prospects. This is attributed to greater unmet resident health care needs along with the effect of healthy economic advances, and the public commitments to boost health-related standards.
Global first aid kits market comprises numerous small-specialised operators and a few large players. Key players include 3M, Acme United Corporation, Beiersdorf AG, Certified Safety Manufacturing, Fieldtex, First Aid Only Inc, HARTMANN Group, and Johnson and Johnson among others.
Customer needs and key success factors
As highlighted in the three previous sections, there are good market perspectives for both local haemostatic products, also in first aid kits and in laser based medical devices. However, in order to evaluate the real market potential of the LIGHT+TER device, it is worth investigating the real point of view of potential customers representative of the market segments addressed by the project, understanding their needs and expectations from a new device for self medication or for ambulatory surgery.
To do this, we have identified two possible customer profiles which well represent the possible end users of the two versions of the LIGHT+TER device:
(a) young women or men with children for the portable device;
(b) dentists for the tabletop device.
For these two customer profiles, we constructed an empathy map, which evidences the aspirations, needs feelings and potential problems to be solved for a specific customer, representative of a whole customer segment. Empathy Map was developed by visual thinking company XPLANE and helps to better understand the customer environment, behaviour, concerns, and aspirations, allowing to identify the strong points of the offer and more convenient ways to reach customers. Ultimately it allows you to better understand what a customer is truly willing to pay for.
To construct the empathy map, we answered to a series of questions on the specific customer profile, also asking directly to people of these categories if necessary. Below are the results for the two types of customers.
According to the above table, it is possible to identify the main market drivers that would lead to the use of new products for haemostasis and fast small traumatic wound healing, both in daily life and in a surgical and medical context, also by people without particular coagulation problems. To address the needs of women with children for example, important characteristics of a new device for superficial wound care would be:
(a) the ease of use;
(b) the improved healing time;
(c) the reduction of scars;
(d) the compactness;
(e) the competitive price with respect to existing products.
The LIGHT+TER portable device will have all the required characteristics, being user-friendly, with a very simple user interface, inducing haemostasis in less than 30 seconds without damaging the surrounding tissues, and hence minimising the presence of scars. Although the price will be higher than standard haemostatic patches or dressings, it will be however competitive, as the device can be reused many times, just changing the biodegradable plaster, sent separately at a very small price. Furthermore, the price foreseen is comparable with that of other electronic biomedical devices commercialised as over the counter products, as for example IR thermometers, that are often used for children. Another key success factor for the portable device, apart from its technical characteristics (as selectivity and reduced healing time), could be the growing environmental consciousness among European population, who may prefer to buy a single device instead of disposable products, if the performances are the same or even better.
The characteristic of the LIGHT+TER portable device makes it also extremely interesting to be included in first aid kits, in schools, fitness centres, grounds or soccer fields, providing an added value service for the large community. This also represents an important potential market for the device, addressing the needs of young women with children for example. As for the market drivers for the optical fibre device, the following aspects appeared to be important criteria for the use of a new haemostatic device or product in surgery:
(a) to prevent excessive bleeding, to ensure safe procedure, and to avoid complications associated with excessive bleeding;
(b) to reduce morbidity thanks to improved procedure, reduced surgery time, and prevention of complications;
(c) to be cost effective and time saving for the medical personnel;
(d) to have aesthetic and perceived benefits for the patient.
The LIGHT+TER optical fibre device satisfies all these requirements, inducing effective haemostasis in small blood vessels, with size up to around 100 - 200 µm, in a very short time, thus reducing the surgery time and minimising complications due to excessive bleeding occurring in small superficial blood vessels. In addition, it minimise the use of suture products having also an aesthetic benefit for the patient, in particular in dermatologic surgery.
In the specific case of dentists, the availability of a tool able to stop bleeding in small blood vessel through a very small probe will be extremely useful, taking into account the reduced space available in oral surgery. The fast haemostasis induced by the LIGHT+TER device will also lead to an important saving of time for dentists, representing another point of strength for the product. In addition, in case of dental surgery, the patients will not have to stop their therapy with anticoagulants, thus preventing even more serious cardiovascular problems. These aspects represent key success factor for the LIGHT+TER optical fibre devices that are even more strengthened by the price aspects: the foreseen cost of the device in fact is extremely low with respect to other similar equipment present in ambulatories for dental treatments or day surgery.
All the above analysis showed that the LIGHT+TER device, in its two versions, has a big potential market also excluding people with coagulation problems due to hereditary diseases or other pathologies. The key success factor will be not only the reasonable expected cost, but also its technical characteristics, able to address the main needs of a large spectrum of potential customers.
Exploitation and dissemination
The technological core of the LIGHT+TER devices in the two versions is the same and it is composed by a LED source with the related optical system, the electronics managing the user interface and controlling the device operation, a power supply and a series of external parts, including case, buttons, etc. Then the over-the-counter device has also a biodegradable plaster to be used as an interface with the wound during the treatment, while the optical fibre device is equipped with an optical fibre and a proper connector.
Preliminary activities beyond the project duration
In order to be able to put the LIGHT+TER devices on the market, a series of activities are required at the end of the project, to ensure their compliance with exiting standards and regulations for medical devices at national and European level.
First of all, in vivo tests will be carried out in the framework of the procedure to obtain the CE marking, in order to validate the clinical efficacy of the device both on healthy patients and in patients with coagulation diseases. The medical structure in which these tests will be carried out will be already selected at the end of the project, and will be indicated in D6.2 to be issued at M24. These tests will be carried out during the clinical trial, after the end of this project, in order to obtain the clinical data able to validate the effectiveness of the device with in vivo data. They will focus on the photocoagulation of superficial abrasions of healthy people under the supervision of a dermatologist; the application of the device on people suffering from coagulation disorders will be also done, under the supervision of a haematologist.
These kind of tests were not foreseen in the project workplan due to the short time frame available and characteristics of this funding scheme (research for SMEs), but need to be carried out as a very first step toward the commercialisation of both devices. Then, having the final device available and tested, the procedure to obtain the CE certification will be completed and, once certified, the marketing of the device could start.
Approach to market
Although the project coordinator L4T owns the patent which is at the basis of the project idea, an agreement has been reached between the prime proposer and the other SMEs in the consortium to license to them the manufacturing and exploitation of the sub-systems and consumables. In particular:
- Light4Tech will be responsible for the assembly LED array with the related optical system (including optical fibre) and heat sink, starting from commercial LEDs and fibres, and to the integration of the overall system.
- MACROS will realise the control electronics for the LED array and the user interface electronics for the two layouts.
- LEPOLAM will supply the power management system and will produce the components for the final assembly of the device (case, buttons..).
- BS will produce the biodegradable plasters for the portable device.
As anticipated, the initial demand is expected to be satisfied by the SMEs in the project consortium and the device will be produced starting from the components supplied by them, and put on the market by L4T.
However, the expected growth in the demand and their geographical dispersion will be far beyond their joint capability to satisfy it. Thus, it is expected that the LIGHT+TER concept and related technologies will be transferred to a wider industrial community, by selling licenses to companies in the medical device sector, who will commercialise the whole system, and to companies operating in each technological sub-sector who will be suppliers of components, generating royalty revenues.
Distributors will be selected for the different Countries, with whom special agreements will be stipulated in order to define the economical and Intellectual properties conditions.
Description of the supply chain
The supply chain for the LIGHT+TER devices is formed by the producers / integrators of the single components which constitutes the device.
In the first stages after the commercialisation of the system, the companies involved in the project activities and in the development of the device will be the main suppliers of components and thus the main players in the supply chain. In particular:
- Light4Tech will be responsible for the assembly LED array with the related optical system (including optical fibre) and heat sink, starting from commercial LEDs and fibres, and to the integration of the overall system.
- MACROS will realise the control electronics for the LED array and the user interface electronics for the two layouts.
- LEPOLAM will supply the power management system and will produce the components for the final assembly of the device (case, buttons.).
- BS will produce the biodegradable plasters for the portable device.
As anticipated, the initial demand is expected to be satisfied by the SMEs in the project consortium and the device will be produced starting from the components supplied by them, and put on the market by L4T. However, the expected growth in the demand and their geographical dispersion will be far beyond their joint capability to satisfy it. Thus, it is expected that the LIGHT+TER concept and related technologies will be transferred to a wider industrial community, by selling licenses to companies in the medical device sector, who will commercialise the whole system, and to companies operating in each technological sub-sectors who will be suppliers of components, generating royalty revenues.
Distributors will be selected for the different countries, with whom special agreements will be stipulated in order to define the economical and Intellectual properties conditions. Industry cost structure.
Having described the supply chain for the final production of the LIGHT+TER devices, it is possible to estimate their final selling price, taking into consideration the estimated production costs for each subcomponent, and other expenses that will be sustained by the companies involved in the commercialisation, as for example costs for the CE mark procedure, costs for clinical evaluation etc.
The estimation of the final price of the LIGHT+TER device allows to better understand the competitiveness of the product on the market as well as its sells potential. Furthermore, together with the analysis of the market trends, it can help to identify which one of the two layouts will be more promising in terms of market potential. Table 3 below reports a realistic forecast of the initial costs for the components required to assembly the two versions of the LIGHT+TER LED device. The two values indicated refer to a prototype production (higher value) and to a volume production of 100 000 units.
The costs presented refer to the core of the LIGHT+TER device, without optical fibre, and have been estimated taking into account that increasing the production volume, the cost of the components will be drastically reduced, even in case of the LED module, which is the most expensive part of the device.
According to these data, the cost of the LIGHT+TER device in the over the counter version will be about EUR 215 in the prototype phase, but will be reduced down to EUR 35 in case of a production of 100 000 units, leading to a selling price of about EUR 50 - 60. This price is actually higher than haemostatic patches and common dressing, but it can be affordable taking into account the many advantages with respect to existing products, as for example the fact that it is reusable.
As for the optical fibre device, the component cost will be similar to that of the portable device: only a slightly higher cost can be foreseen for the user interface electronics, but the incidence on the final price will be very small. In addition, the cost for the optical fibre bundle and the connector must be added, which can be estimated in about EUR 100 for small volumes, to be reduced to EUR 40 for large supply volumes. In this framework, as a realistic forecast one can estimate that the optical fibre device will be put on the market with a price of about EUR 200 - 250, extremely low with respect to other instruments used in dental ambulatories or during day surgery.
The estimated selling price for the two devices has been calculated adding 30 % to the estimated components costs to account for investments for marketing, promotional campaign, costs for assembly and packaging, and for obtaining CE mark and certifications. Taking into account these values and the potential end users, it can be estimated that after a promotional campaign, within 5 years from the end of the project, leading to about 500 000 pieces sold, the revenue for the LIGHT+TER portable device could be projected to be about EUR 25 million. This estimation can be even larger for the system with the optical fibre, where the end users are dentists, first aid organisations, hospitals, ambulatories and centres for day surgery.
Distribution channels
Taking into account the large market potential emerged from the present analysis, the SMEs in the consortium agrees on the need to transfer the LIGHT+TER concept and related technologies to a wider industrial community by offering licenses all over Europe and generating royalty revenues. Preliminary discussions are being carried out under non-disclosure agreements with other European companies involved in medical device production and distribution which thus would contribute to LIGHT+TER penetration. Licenses negotiations will be carried out as soon as the market demands will be generated, which is expected to be after the fifth year since LIGHT+TER commercialisation.
During the commercialisation phase, three business routes will be followed, in order to ensure an effective take up from the market of wound care, haemostatic products and laser medical devices:
- The direct selling of the LIGHT+TER device to the end users, to be carried out in the first promotional phase, when production volumes will be small.
- Sale of the single components to companies interested to assembly the final device, upon opportune licensing of the whole LIGHT+TER concept: this strategy would be interesting in order to penetrate in the market in a more effective way, exploiting the visibility of larger medical companies.
- Licensing of the concept of single components to other companies in the medical device sector on a case by case basis: this route will be effective when production volumes will increase as a consequence of a growing market demand and large companies will have larger production facilities.
As for the distribution channels to the end users, there will be two main routes to reach a the community of end users, taking into account the product characteristics. The portable device, as already discussed, has been conceived as an over the counter product, and thus it will be sold in pharmacies or shops specialised in sanitary and medical products. In this case, the company in charge for device assembly will be responsible for distributing the product, unless the distribution will be carried out by other distribution companies selected for each country.
The optical fibre device instead, being used mainly in hospitals, ambulatories, dentists, will be put in commerce directly by the company in charge of the assembly, who will interact directly with end-users through sales representatives.
List of websites: http://www.lightplaster.com(odnośnik otworzy się w nowym oknie)
