Final Report Summary - DIMIDPLUS (Commercialization of an Innovative Microfluidic Impedance-based Device for multi-parametric cell analysis)
Executive Summary:
Based on the scientific results of its predecessor project DIMID GAo286692, the DIMIDplus project GAo606100 has successfully commercialized a novel, highly innovative technology for multi-parametric single cell analysis based on impedance flow cytometry.
While this new methodology was already scope of researchers for several years, the DIMIDplus project could demonstrate for the first time the successful transfer of this innovation to the markets. The competitive advantages compared to traditional approaches like fluorescence based flow cytometry could be shown for several applications.
Haematology Milk Analysis Pollen Analysis
Haematology Milk Analysis Pollen Analysis
• Reduced complexity and cost for diagnostic applications
• Reduced footprint to enable point-of-care applications
• Portable devices enabling to be used for emergency applications
• 100% label free • Reduced complexity
• No sample preparation
• Analysis of raw milk directly at the farm
• Footprint and portability • Today, the only reliable and the most cost efficient methodology available to measure pollen viability
• Footprint and portability
Besides the commercialization of three specific applications, the project produced a new, highly innovative measurement instrument, the MFLI. This instrument is a versatile lock-in amplifier and impedance analyser, which serves typical physics and biology applications like optical chopper and pulsed laser applications, scanning microscopy, material research and impedance spectroscopy for single cell analysis. The measurement instrument is sold as a bench-top, stand-alone product on the one hand or for integrated applications as an OEM version on the other hand.
Project Context and Objectives:
Cell analysis has become an important technique and represents a fast growing market for a wealth of applications in the fields of life sciences, medicine, environmental, dairy and greenhouse analytics. Clinical (diagnostic) and research applications in the healthcare and drug discovery markets demand rather complex analyses at the single cell level, whereas routine and quality control applications in bioprocess monitoring must presently content themselves with simpler, quicker and cheaper analyses.
What these markets are calling for is a device comparable to the high-end solutions, allowing faster and less expensive analyses and therefore offering a valuable alternative for the more price-sensitive applications, or for real-time cell culture monitoring, for which high-content analyses are presently not available.
In the context of the DIMID project GAo286692, the technology to build such a device has been developed by a highly specialized Consortium consisting of both RTD and SME performers. At the end of the project, a prototype has been produced which has been successfully tested for selected applications like haematology and dairy food quality analysis. The results obtained have carefully been analysed and were benchmarked against competing technologies. Finally, a business plan was developed depicting a roadmap how to commercialize the DIMID prototype and some of its sub-components. Under GAo 606100, a follow-up project proposal called DIMIDplus has been submitted. This report details the results of the last 12 months of this demonstration activity project.
The consortium of the DIMIDplus project consists of all formerly involved SMEs (ZURICH, CELLIX, CYTOGNOS) and is complemented by LABS64 (IT provider, specialized in software quality, verification and testing) and AMPHASYS (single-cell electrical impedance technology leader and IPR holder) to commercialize the DIMID device and the electronic unit by verifying their performance, further testing to increase reliability, checking CE conformity and product packaging.
An important concept of the DIMIDplus project is to manage risks for the SMEs involved. As usual when working on high-potential, high-tech products there is a significant risk attached to each application. For this reason the DIMIDplus project aims at exploiting the developed technologies for multiple applications and markets. This is happening at multiple levels. First ZURICH, a supplier of technology for the DIMID device, will not only deliver the electronics to the end integrator CELLIX but ZURICH will also market the technology directly. This significantly reduces the risk for ZURICH. Secondly, AMPHASYS and CELLIX are targeting multiple applications like haematology assays, dairy quality control and pollen quality control. This again spreads the risk over several fields of applications.
Following on the DIMID project, the commercial objectives of the DIMIDplus project are set out as follows:
In order to reach those objectives, a step-by-step plan consisting of 12 strategic goals have been defined:
Specific activities devised into five work packages were carried out in order to obtain the goals mentioned above. Two work packages (WP 1 & WP 2) were dedicated to technical work, two work packages (WP 3 & WP 4) had commercial focus and one work package (WP5) was dedicated to project management. In the following, for each of the work packages WP 1 – WP 4, the specific sub-goals as initially defined along with the project plan are shown.
Objectives and plan for WP1 – Industrialization of “ETZEL”
• Increasing stability and usability of the software in line with commercial requirements
• Set up SW verification and regression environment
• Validating the final hardware of ETZEL
• Set up calibration environment and implement calibration and burn-in tests
• Submit deliverables D1.1 “ETZEL Device” and D1.2 “ETZEL Documentation”
Objectives and plan for WP2 – Preparation for Market “DIMID”
• Execution of the RBC and WBC assay according to deliverable D2.1 “Validation Plan”
• Execution of the greenhouse and milk assay according to the validation plan
• Finalization of the DIMID haematology device to achieve demonstration level
• Finalization of the DIMID pollen analysis and dairy device in line with commercial requirements
• Integration of additional SW requirements into DIMIDSoft for the DIMID greenhouse and dairy device
• Submit deliverables D2.2 “DIMID Device” and D2.3 “DIMID Documentation”
Objectives and plan for WP3 – “DIMID” Commercialization and Marketing
• Define and submit the business plan D3.1 “Business Plan”.
• Deliver D3.2 “Patent Search”: Carefully monitor the risk of patent infringements.
• Submit deliverable D3.3 “Report on Scale-up and Supply Chain Management”: The DIMID and ETZEL contain several critical components, which require careful risk management of the supply chain.
• Submit deliverable D3.4 “Product Folder”: all marketing material need to be ready for the respective product launches, namely leaflets, brochures, specifications, advertisements and product web sites.
• Implement, test and document the web shop, submit deliverable D3.5 “Web Shop”.
Objectives and plan for WP4 – Trainings and Customer Demos
• Prepare training material and perform customer demonstrations
• Submit the deliverables D4.1 “Training Material” and D4.2 “Report on Customer Demos”
Project Results:
Results achieved under WP1 – Industrialization of “ETZEL”
Main focus of this work package was on the preparation of the market launch of the ETZEL measurement instrument. A major part of the staff of Zurich Instruments was working in parallel on creating marketing material, commercial ads, product user and programmers manuals and product videos. In parallel, the ETZEL hardware and software validation tasks were taking most of the attention. On the hardware side, two further design spins were required mainly with the focus on noise performance improvements. On the software side, there were three areas of focus, which were executed in close collaboration with the consortium partner LABS64: functional verification including setup of a complete regression environment, increased stability and improved usability. For the latter one, a graphical view of the main lock-in tab was added to the LabOne measurement software package. Other activities focused on the scale-up of the manufacturing and warehousing processes. The anticipated sales volume of the MFLI required the introduction of a company wide ERP system including the setup of a web shop. Both systems were defined, implemented and verified during the second period of the project. On January 30th, 2015, Zurich Instruments launched the ETZEL under the brand name MFLI to the market. All product is found under:
http://www.zhinst.com/products/mfli.
All deliverables of this work package were submitted on time, namely the ETZEL device and documentation.
D1.1 “ETZEL Device”:
For more information on the product, a short video is available under:
https://www.youtube.com/watch?feature=player_embedded&v=5ihQH0hCmr4
The new product is intended to become the new standard for lock-in amplifiers in the frequency range of up to 500 kHz challenging the current market leader, the SRS 830:
The MFLI product comes along with an outstanding tool set: LabOne.
D1.2: “ETZEL Documentation”
The MFLI comes with a detailed set of user documentation. For detailed information, please refer to:
http://www.zhinst.com/products/mfli.
Results achieved under WP2 – Preparation for Market “DIMID”
In work package two, the consortium partners CELLIX, AMPHASYS and CYTOGNOS worked in parallel on the market preparation for their products.
D2.1 “Assay Validation”
The main focus on CELLIX side was on the RBC and WBC haematology assay validation including creation of a draft project plan on how to achieve IVDD certification:
In parallel, the portable DIMIDplus haematology analyser was further integrated and brought to a stage where it can be deployed to potential OEM partners. First clinical tests with volunteers were setup. On January 29, CELLIX successfully demonstrated the DIMIDplus haematology device at the premises of Zurich Instruments in the context of a F2F consortium meeting. Blood of several volunteers of Zurich Instruments was measured demonstrating the performance of the device and assay including the analysis of cell populations with the DIMIDsoft provided by CYTOGNOS.
On the side of AMPHASYS, the key activities were related to the validation of the assays for pollen analysis and dairy food applications.
The first priority was on the successful launch of the pollen analysis assay. For the determination of pollen viability no standard method exists. Individual seed companies have developed their own protocols that rely basically on some published data and depend, of course, on the sort of pollen to analyse. Most seed companies have validated the AMPHASYS technology with their methods, but do not want to disclose the data.
However, analyses were performed at 0.5 and 12 MHz and compared with pollen stained with FDA/PI (Fluorescein Diacetate / Propidium Iodide), a fluorescence dye mixture that selectively reveals viable and dead cells by fluorescence microscopy. Pictures of the stained samples are taken, the green (DAPI, viable) and red (PI, dead) cell counted and the obtained ratios compared with the analyses performed with the DIMIDplus device. A very high correlation between both methods could be demonstrated.
Based on the excellent results, AMPHASYS successfully launched the DIMIDplus device for pollen analysis, named as AMPHA Z30 to the market in April 2014.
During the last 6 months of the project, AMPHASYS increased its focus on the milk assay. Several laboratories were contacted and the device was demonstrated to customers in Switzerland and France. The performance of the assay continuously improved and was finally benchmarked against traditional, optical based technologies. An evaluation of the technology was done with a prototype of the AMPHA Z30. Samples were measured at the facility of Amphasys and at Swissmilk (Zollikofen, CH). The data provided evidence of a good correlation between the DIMIDplus for somatic cell count on raw milk and the Fossomatic device, which is considered to be the gold standard.
D2.2 “DIMID Device”
During the DIMIDplus project, both CELLIX and AMPHASYS further improved their DIMID devices. Below the pictures are shown for the portable DIMID haematology analyser that is used as a demonstrator for potential OEM partners and the DIMID device for pollen analysis and dairy food applications.
D2.3 “DIMID Documentation”
This document was written in tight collaboration with CELLIX, AMPHASYS, ZURICH and CYTOGNOS. It contains three main sections, which are related to the DIMID device for haematology, the DIMID device for pollen and milk analysis and the DIMIDSoft impedance flow cytometry analysis software.
a) DIMIDplus Portable Device for Haematology
The documentation part for the DIMIDplus portable device for haematology has been made available and serves as a base for further steps towards final commercialization in collaboration with a potential OEM partner. In particular, it contains all information about the sub-systems of the device, the validation results of the RBC and WBC assays and a roadmap towards IVDD certification.
b) DIMIDplus Device for Pollen Analysis and Dairy Food Applications
The documentation part for the DIMIDplus device for pollen analysis and dairy food applications has been made available and serves as a base for manufacturing. In particular, it contains all information about the sub-systems of the device and the validation results of the pollen and milk assays.
c) DIMIDSoft Analysis Software for Impedance Flow Cytometry Data
The documentation part for the DIMIDSoft analysis software for impedance flow cytometry data has been made available. It describes an overview of the software architecture. Even if DIMIDSoft scope was not foreseen to pass a potential IVD certification audit, the ISO: 13485 and UNE: 62304 SOPs implemented at CYTOGNOS for software design and development would allow complying with IVD requirements rather straightforward.
Results achieved under WP3 – Commercialization and Marketing
The work performed in work package three included mainly the study of the relevant markets and the preparation of marketing material like product folders and videos and the scale-up for production ramp-up of the various devices.
All deliverables of this work package were submitted on time or with a minor delay.
D3.1 “Business Plan”
A detailed business plan was defined based on several market studies performed. A lot of emphasis was put on understanding the competitor landscape for the various technology offerings:
Competitive comparison haematology analyser market:
Company Cellix Samsung Abbott Horiba Sysmex
Device DIMIDplus
LabGeo HC10
Cell-Dyn Emerald
HHi 2K,en Derzlic
pocH-100i
Dimensions (HxWxD) 10.6” x 11.8” x5.9”
27 x 30 x 15(cm) 14.5” x 13.5” x 11.5”
39 x 34.4 x 29.3 (cm) 13.8” x 9.8” x 13.8”
13 x 25 x 35(cm) 16.5” x 14” x 12.5”
41.9 x 35.6 x 31.8 (cm) 7.3” x 13.8” x18.1”
18.5 x 35 x 46
Weight (lbs/kg) 5.5lbs / 2.5kg 28lbs / 12.8kg 20lbs / 9kg 31lbs / 14kg 30.8lbs / 14kg
List Price €6,000 / $8,000 €2,800 / $4,841 *Source: http://www.medicalequipmentcentre.com/
€22,000 / $30,000 €16,500 / $22,500 €13,200 / $18,000
Used N/A Unknown €3,700 – 5,900 / $5,000 €4,400 / $6,000 €1,800 / $2,500
Parameters RBC, WBC & WBC-3 diff. 18 parameters:
WBC-3 diff, WBC, LYM, MON, GRA, LYM%, MON%, GRA%, Hb, HCT, RBC, MCV, MCH, RDW, MCHC, PLT, PCT, MPV, PDW 18 parameters: WBC, RBC, Hb, Hct, MCV, MCH, MCHC, PLT, %&# neut, mono, lymph, eos, baso CBC Mode (16 parameters): WBC, RBC, HGB, HCT, MCV, RDW, MCH, MCHC, PLT, MPV,*PCT,*PDW, % and # of LYM, MON and GRA Whole blood mode: 17 parameters with 3-part Differential
Pre-dilute mode: 8 Parameters, which includes WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT
CV 3% WBC count
3% RBC count 1.6% WBC count
1.3% RBC count
0.8%Hb
3.3% platelet 3.5% WBC count
2.0% RBC count
2.1%Hb
6.1% platelet
1.7% Hct
0.8% MCV 2.5% WBC count
2.0% RBC count
1.5%Hb
5% platelet (WB or PLT concentrate)
2% Hct
Min Volume 25 µL 25 µL 9.8 µL 10 µL 15 µL
Time to result ~60 seconds 45 seconds
Sample type EDTA whole blood EDTA whole blood WB, PRP WB and pre-dilute
Throughput Unknown 80 samples / hr 60 samples / hr 60 samples / hr 25 samples / hr
The demand for haematology analysers is influenced by the development of alternative technologies such as point-of-care (POC) instruments and integrated analysers, advancements in product automation and highly streamlined lab processes. Cell analysers presently available for lab purpose are multi-channelled, as they analyse various haematology measurements utilizing diverse techniques. A number of patients prefer home monitoring devices.
Developing products by integrating complementary technologies such as imaging, software, HT and multiplexing in compact bench top flow cytometers, which may target POC markets can help market players gain a substantial boost in sales. Existing players have already started considering the importance of automation and sample handling; however, there is still a lot of scope in this space, as developing flow cytometers with integrated sample automation can save costs significantly by reducing the amount of sample volume and offering HT. Also, automation can enable rapid data exchange across different systems. With increasing focus on the need for HT, there would also be a continuous need for advanced software that can analyse and manage the large amount of data generated. Thus the market players can tap this opportunity. The DIMIDplus haematology device is a small, portable, low-cost system, which can target applications in point-of-care settings such as:
• Emergency rooms where devices may need to be moved to the patient bed-site
• Mobile first responders including air and ground ambulances
• Remote medical centres or satellite hospitals.
• Doctor’s office
The attractiveness of the compact footprint of the DIMIDplus device was echoed during interviews with key stakeholders. Further benefits of the DIMIDplus haematology device include leveraging the microfluidic nature of the device thereby enabling the targeting of specific patients such as neonates and children where typical blood volumes are in the region of 1-4mL.
Going forward, the global market for in vitro diagnostic products will remain captive to the growing and significant financial challenges facing health care delivery systems as population age and underserved populations demand improved care. The advent of Obamacare in the US is expected to particularly constrain service and product pricing in that nation as the delivery system attempts to accommodate significantly more patients, many of whom have the expensive “triad” of diseases – obesity, diabetes, and hypertension. Other developed nations will also be coping with aging, sicker populations, pushing their health delivery systems to the limits. For these reasons, health care systems and players are looking for disruptive technologies that significantly reduce costs, significantly improve health care or preferably do both. This will raise the bar for companies seeking to develop blockbuster products, as technologies that offer incremental improvements will not see broad application.
On the risk side to enter these markets, the regulatory constraints need to be well understood. In Europe, the Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices and successive amendments and corrections, aims at creating a single market and reducing technical barriers to trade for medical devices. It introduces common regulatory requirements for IVDs across Europe, bringing IVDs in line with other medical devices. The Directive lays down harmonising rules designed on the safety, quality and performance of IVDs. In the USA, the procedure on how to market a diagnostic device is well explained on the FDA website:
http://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/default.htm
Comparative comparison milk analysis:
The quality of milk is among others assessed by counting the number of bacterial and somatic cells. Current analytical instruments are too complex and expensive (instruments and assay costs) for most dairy food producers. Therefore, thousands of samples are screened daily by simple qualitative tests, which occasionally fail causing costly production losses.
Ampha Z30 represents a low-cost, easy-to-use device that can be used for both bacterial and somatic cell counting. So far, there is no solution on the market for a simultaneous count of bacterial and somatic cells. Amphasys’ technology could fill that gap and achieve a comfortable position if the analysis is possible directly on raw milk. In the course of the DIMIDplus project, this was successfully demonstrated.
In contrast to the haematology market described above, somatic and bacterial cell counting of raw milk is not subjected to severe regulatory norms. The qualification of the product quality, however, is clearly defined and regulated, which means that cell counters do need to fulfil counting precision and accuracy criteria for being used in the qualification process. The technology must therefore prove to meet the specifications of the established and accepted analysers (from FOSS or Bentley Instruments), which will require regular calibrations and validations of the systems.
The development of a specific sales force for the milk analysis application seems not to be the optimal choice for penetrating the market. Partnering with one of the larger companies (FOSS, for example) as an OEM supplier would provide a much faster access to this large market.
Comparative comparison pollen analysis:
Presently, the only alternative to determine pollen viability is either using fluorescent dyes and counting the cells with microscopes, or performing germination assays, which however take a lot of time. Amphasys’ impedance flow cytometer will clearly fill this technological gap. The table below lists current technologies used and compares it with Amphasys’ solution.
Technology Impedance Flow Cytometry Fluorescence microscopy In vitro germination
Device Ampha Z30 Fluorescence Microscope Petri dish
Throughput 20 analyses / h 6 analyses / h 100 analyses / day
Reproducibility High Low Low
Analysed cells / test 10’000-50’000 < 50 < 50
Reliability High Low Low
Specificity towards pollen types Low High High
Suitability for greenhouse Yes No Not effective
Portability Yes No Yes
(A) Pollination results expectedly in no fruits at all. (B) Correlation between measured pollen viability and production of embryos, which generate new plants. (C) Typical seed setting curve for tomato resulting from pollen viability analysis with Amphasys’ device.
D3.2 “Paten Search”
The patent search was executed by CELLIX with support of AMPHASYS. The study was executed taking into account the key objectives of the DIMIDplus project and subsequently distributed to the DIMIDplus consortium in order to avoid possible patent infringements. This study acted as well as an aid for the consortium to define an appropriate IPR protection strategy.
D3.3 “Report on Scale-Up and Supply Chain Management”
The work on a scale up concepts and basic supply chains for all three products resulting out of DIMIDplus has been reported in D3.3 “Report on Scale Up and SC Status”. The DIMIDplus Consortium has a highly interlinked supply chain strategy with strong mutual dependencies.
All partners have performed a detailed risk assessment creating awareness of their supply chain dependencies and how this might impact their ramp-up schedule. Where possible, a second source supplier has been defined. However, this was not feasible for all critical parts of the respective products.
In order to mitigate those risks, the partners are currently negotiating OEM respectively license agreements for critical parts that have no obvious alternative for second source supply.
D3.4 “Product Folder”
All partners developed marketing material for their respective products. Below a small excerpt of the respective product folders:
Product Folder MFLI:
Product Folder DIMID device for haematology:
Product Folder AMPHA Z30:
Product Folder DIMIDSoft:
For further information, please refer to the relevant product pages:
• http://www.zhinst.com/products/mfli
• http://cellixltd.com/products
• http://www.amphasys.com/impedance-flow-cytometry
• http://www.cytognos.com/dimidsoft
D3.5 “Web Shop”
The MFLI is the third product platform of ZURICH and covers the frequency range of 50 kHz to 5 MHz. It has been launched to the market January 30th, 2015 under the brand name MFLI. The MFLI platform has the potential to reach a sales volume of 1000 units per year by end of 2018.
This strong growth requires dedicated strategies, which target on:
• Efficiency of the pre-sales, sales and post-sales processes including provision of a webshop
• Efficiency and scale-up of the supply chain including manufacturing and warehousing
As a consequence, ZURICH decided to define an IT Integration strategy, which has been implemented and is reflected in the deliverables D3.3 “Report on Scale-Up and SCM” and D3.5 “Webshop”.
At the end of the DIMIDplus project, two essential elements of this strategy are now available: the Webshop and the ERP manufacturing and warehouse modules.
With those two elements in place, ZURICH is prepared to successfully execute the manufacturing, warehousing and sales processes for up to 1000 MFLI units per year.
At the time of taking the screen shots, the webshop was still undergoing tests and was hosted on a test environment: ziweb2/deploy/droducts/mfli (the test environment is not visible to the outside world)
Results achieved under WP4 – Training and Customer Demos
This work package only started in project period two. Apart from LABS64, who are not planning to deploy a commercial product within the scope of DIMIDplus, all consortium partners prepared and executed several trainings and customer demos.
This work is documented in detail within the deliverables “Training Material” and “Report on Customer Demos”. Leaflets, user manuals and application notes can be found as well on the respective home pages of the partners. Both deliverables of this work package were submitted on time or with a minor delay.
D4.1 “Training Material”
All training material required to conduct trainings and to perform customer demos has been made available. The deliverable D4.1 “Training Material” has been submitted in Month 16 with a delay of one month. Although this deliverable has been submitted, new training material is constantly being generated.
The table bellows shows a summary of the training material that has been made available:
ZURICH CELLIX AMPHASYS CYTOGNOS
Technical Specifications Technical Specifications AmphaZ30 User Manual Technical Specifications
Quick Start Guide Videos AmphSoft User Manual User Manual
Tutorials Quick Start Guide
Functional Description Webinars
Programmer Manual
Application Notes
Videos
D4.2 “Report on Customer Demos”
The product launches of the ETZEL under the brand name MFLI and the DIMID device for pollen analysis under the brand name AMPHA Z30 occurred in January 2015 and April 2014, respectively. For both products, ZURICH and AMPHASYS did numerous customer demonstrations, either during product fairs or directly on-site with customers. For the DIMID device for milk analysis, AMPHASYS did so far one demonstration. More customer demonstrations will follow in the second half of 2015. On CELLIX side, the focus in the second period was still on assay validation. Results of the validation stage were presented to numerous potential OEM partners, but so far on slides only. Demonstrations with the actual device are planned to occur in the second half of 2015. CYTOGNOS demonstrated DIMIDSoft so far only to Consortium internal stakeholders.
Results achieved under WP5 – Project Management
The project management main focus was on tracking the overall progress of the project towards the end of the period. The critical path towards the end goals of the project was constantly monitored and optimized by frequent Skype calls, and where required, by F2F meetings. On top of this, a common platform for information sharing was installed (Confluence). Work shared between partners was tracked and documented there.
While some of the project tasks could be executed quite independently by the individual partners some other tasks required very close alignment and task interfaces between partners had to be carefully reviewed and constantly optimized. Most challenging was the final integration of the product components provided by ZURICH, AMPHASYS and CYTOGNOS into the final version of the DIMIDplus haematology of CELLIX. For this reasons, dedicated handover Skype calls were organized, in particular between CELLIX and ZURICH. A final handover of the ETZEL electronic unit to CELLIX was successfully performed beginning of November 2014 during a handover and training session taking place in Dublin.
During the second period of the project, more and more focus was put on exploitation and on dissemination, which is reflected in the list of deliverables below. All deliverables of this work package were submitted on time without any delay.
D5.1 “Consortium Agreement”
The Consortium Agreement was negotiated at the very beginning of the DIMIDplus project and signed by all partners in December 2013.
D5.2 “Draft PUDK and D5.3 Final PUDK”
Dissemination of knowledge of projects funded under the FP 7 is an obligation, but also an opportunity to increase the expected impact and visibility of the project outcome. For a demonstration project such as DIMIDplus, where final products ready to be marketed are the expected outcome, dissemination activities are even more important than in R&D projects. WP3 Commercialization and Marketing and WP4 Training and Customer demos of the present project are already including major dissemination activities and are therefore just briefly mentioned in this deliverable. Besides those, the deliverable contains an IP strategy followed in this project.
D5.4 “Exploitation Agreement”
One of the key deliverables of project management during the second period of the project was to negotiate and finalize the exploitation agreements among all partners. IP and OEM partnership agreements not detailed in the Consortium Agreement had to be clarified and resulted in complementing exploitation agreements.
Potential Impact:
The DIMIDplus project has bridged the gap between research and market by investing a joint effort of five SMEs to commercialize a high-tech, high-potential technology. The consortium has formed a highly linked business model focussing on six business opportunities:
During the DIMIDplus project, the five partners have further built and strengthened their core competences:
In the following section, the achieved commercial results of all SME and the wider impact are summarized:
Commercialization Opportunity 1: ZURICH – Physics Research
The ETZEL has been commercialized and launched under the name MFLI as instrument dedicated to Physics Research on January 30, 2015. The product can be found and ordered under http://www.zhinst.com/products/mfli. The MFLI sets the new standard for measurements in the medium and low frequency range and is available in two versions: DC to 500 kHz and DC to 5 MHz (an upgrade from 500 kHz to 5 MHz is possible later). The MFLI combines superior performance with the outstanding LabOne® toolset. The embedded data and web servers allow straightforward connection to any device running a web browser.
Typical Physics applications are:
• Optical chopper applications
• Pulsed laser applications (e.g. high power lasers)
• Materials research
• Quantum- and Nano-electronics
• Materials research
• Scanning tunnelling microscopy
• Low temperature physics
• Impedance spectroscopy
• Seismic measurements
Commercialization Opportunity 2: ZURICH – Biology Engineering and Research
The MFLI is commercially available and can be purchased in a 5 MHz and a 500 kHz version. Customers that initially purchased a 500 kHz version can upgrade their device later to 5 MHz by purchasing the MF-F5M frequency extension option. Furthermore, a MF-MD multi-demodulator option is available. Both options together turn the MFLI into a powerful instrument for impedance spectroscopy serving the biology engineering and research markets.
Socio-economic Impact and wider societal implications (Opportunity 1 & 2):
• Creation of 15 job opportunities directly at Zurich Instruments within the next 3 years
• Creation of up to 25 job opportunities with suppliers of Zurich Instruments within the next 5 years
Dissemination Activities (see Annex for more details)::
• Strong representation at several exhibitions during the product launch in February and March 2015
• Press releases
• Videos
Exploitation Results (see Annex for more details):
• Two commercially available products MFLI 500 kHz and MFLI 5 MHz.
• LabOne measurement software, trademark submitted and registered in September 2014.
Commercialization Opportunity 3: AMPHASYS – Seed and Pollen Analysis
The AMPHA Z30 is commercially available and can be purchased under http://www.amphasys.com. This instrument is being used for many research applications like bacterial analysis, apoptosis or cell differentiation (cancer and stem cell research) as an alternative to conventional, fluorescence-based flow cytometers. Besides the classical research applications, AMPHASYS is also focusing its activities on industrial applications, where the company sees a huge potential for the technology.
The reliable determination of pollen quality is a key success factor in the seed production process. Experiments show a clear correlation between the viability (also called vitality) of pollen used for pollination and the obtained seed yield. External factors such as light, rain, temperature or chemical agents may influence pollen viability. Amphasys provides an easy method to monitor pollen viability and thus a powerful tool to optimize the plant breeding and seed production process. This is particularly important if laborious manual steps are involved and if pollen needs to be stored or transported from one site to another. The technology can be used on-site, directly in or near the greenhouse.
The product has been launched in April 2014. AMPHASYS has received several orders and is shipping the device to customers.
Commercialization Opportunity 4: AMPHASYS – Dairy
For the milk industry, the quality of raw milk is a major concern. High somatic cell counts mainly caused by bacterial infections and bacterial contamination caused by insufficient equipment sanitation or insufficient cleansing of the cow's udder and teats have an adverse impact on the milk products. Amphasys’ technology allows a direct determination of the somatic cell count in untreated raw milk. The product will be launched in the second half of 2015. AMPHASYS is in contact with several customers interested in the dairy application and first orders are likely to materialize in the end of 2015.
Socio-economic Impact and wider societal implications (Opportunity 3 & 4):
• Creation of several job opportunities directly at AMPHASYS and as well at their suppliers
• Increased efficiency of seed and crop production through availability of a new technology that can reliably measure pollen viability
• Improved herd management for farmers by efficient and cost effective monitoring of the somatic cell count of raw milk
Dissemination Activities (see Annex for more details):
• Press releases
• Conferences
• Videos
Exploitation Results (see Annex for more details):
• Commercially available product AMPHA Z30
• Single cell analysis software AMPHAsoft
Commercialization Opportunity 5: CELLIX - Non-IVD Haematology applications
The DIMIDplus portable device for haematology may be marketed to the non-IVD scientific research market. This business case has not been actively pursued within the DIMIDplus, but remains a valid business option.
Commercialization Opportunity 6: CELLIX - Haematology diagnostics (OEM)
The DIMIDplus portable device for haematology diagnostics is available for demonstration to research customers and potential OEM partners. Due to its complexity, this commercialization opportunity has received the highest attention within the Consortium, as it required the close cooperation of all partners. CELLIX has entered negotiations on deploying the new technology to several diagnostics partners.
Socio-economic Impact and wider societal implications (Opportunity 6):
• Strongly depending of future collaboration with potential OEM partners
• Full scale-up and commercialization of a portable point-of-care device will create a significant number of job opportunities at CELLIX itself, at its OEM partner and at the corresponding suppliers
• The cost advantage over traditional optical based haematology analysers combined with the portability of the device can have a significant impact on personal health coverage for emerging markets and regions with reduced access to hospitals.
Dissemination Activities (see Annex for more details):
• Presentation of the technology at various conferences, e.g. uTAS in Texas, October 2014.
• Videos
Exploitation Results (see Annex for more details):
• Available demonstrator for haematology diagnostic applications targeting RBC and WBC assays
List of Websites:
The DIMIDplus Website has been continuously updated during the project including a new front page with images for pollen and dairy applications, new videos, updated partner’s events participation, press releases and news. Following the EC recommendations FP 7th logo has been substituted by the EU emblem on the DIMIDplus website.
The website maintains a simple and clear structure presenting the outcomes of the DIMIDplus project and the future marketable products. During the entire project, new DIMIDplus brochure, posters and logo have been created with a new refreshing aspect focused on benefits and broad potential applications of the impedance flow cytometry. DIMIDplus brochure and posters are available at the home page.
Contacts of the project partners are listed below:
ZURICH INSTRUMENTS AG Coordinator • Adrian Messmer, VP R&D
• Email: adrian.messmer@zhinst.com
CELLIX LIMITED Partner • Vivienne Williams, CEO
Email: v.williams@cellixltd.com
CYTOGNOS SL Partner • Álvaro Rodríguez, CFO
Email: alrodriguez@cytognos.com
AMPHASYS AG Partner • Marco Di Berardino, Executive Partner
• Email: marco.diberardino@amphasys.com
LABS64 GMBH Partner • Konstantin Korotkov, CEO
• Email: konstantin.korotkov@labs64.de
Based on the scientific results of its predecessor project DIMID GAo286692, the DIMIDplus project GAo606100 has successfully commercialized a novel, highly innovative technology for multi-parametric single cell analysis based on impedance flow cytometry.
While this new methodology was already scope of researchers for several years, the DIMIDplus project could demonstrate for the first time the successful transfer of this innovation to the markets. The competitive advantages compared to traditional approaches like fluorescence based flow cytometry could be shown for several applications.
Haematology Milk Analysis Pollen Analysis
Haematology Milk Analysis Pollen Analysis
• Reduced complexity and cost for diagnostic applications
• Reduced footprint to enable point-of-care applications
• Portable devices enabling to be used for emergency applications
• 100% label free • Reduced complexity
• No sample preparation
• Analysis of raw milk directly at the farm
• Footprint and portability • Today, the only reliable and the most cost efficient methodology available to measure pollen viability
• Footprint and portability
Besides the commercialization of three specific applications, the project produced a new, highly innovative measurement instrument, the MFLI. This instrument is a versatile lock-in amplifier and impedance analyser, which serves typical physics and biology applications like optical chopper and pulsed laser applications, scanning microscopy, material research and impedance spectroscopy for single cell analysis. The measurement instrument is sold as a bench-top, stand-alone product on the one hand or for integrated applications as an OEM version on the other hand.
Project Context and Objectives:
Cell analysis has become an important technique and represents a fast growing market for a wealth of applications in the fields of life sciences, medicine, environmental, dairy and greenhouse analytics. Clinical (diagnostic) and research applications in the healthcare and drug discovery markets demand rather complex analyses at the single cell level, whereas routine and quality control applications in bioprocess monitoring must presently content themselves with simpler, quicker and cheaper analyses.
What these markets are calling for is a device comparable to the high-end solutions, allowing faster and less expensive analyses and therefore offering a valuable alternative for the more price-sensitive applications, or for real-time cell culture monitoring, for which high-content analyses are presently not available.
In the context of the DIMID project GAo286692, the technology to build such a device has been developed by a highly specialized Consortium consisting of both RTD and SME performers. At the end of the project, a prototype has been produced which has been successfully tested for selected applications like haematology and dairy food quality analysis. The results obtained have carefully been analysed and were benchmarked against competing technologies. Finally, a business plan was developed depicting a roadmap how to commercialize the DIMID prototype and some of its sub-components. Under GAo 606100, a follow-up project proposal called DIMIDplus has been submitted. This report details the results of the last 12 months of this demonstration activity project.
The consortium of the DIMIDplus project consists of all formerly involved SMEs (ZURICH, CELLIX, CYTOGNOS) and is complemented by LABS64 (IT provider, specialized in software quality, verification and testing) and AMPHASYS (single-cell electrical impedance technology leader and IPR holder) to commercialize the DIMID device and the electronic unit by verifying their performance, further testing to increase reliability, checking CE conformity and product packaging.
An important concept of the DIMIDplus project is to manage risks for the SMEs involved. As usual when working on high-potential, high-tech products there is a significant risk attached to each application. For this reason the DIMIDplus project aims at exploiting the developed technologies for multiple applications and markets. This is happening at multiple levels. First ZURICH, a supplier of technology for the DIMID device, will not only deliver the electronics to the end integrator CELLIX but ZURICH will also market the technology directly. This significantly reduces the risk for ZURICH. Secondly, AMPHASYS and CELLIX are targeting multiple applications like haematology assays, dairy quality control and pollen quality control. This again spreads the risk over several fields of applications.
Following on the DIMID project, the commercial objectives of the DIMIDplus project are set out as follows:
In order to reach those objectives, a step-by-step plan consisting of 12 strategic goals have been defined:
Specific activities devised into five work packages were carried out in order to obtain the goals mentioned above. Two work packages (WP 1 & WP 2) were dedicated to technical work, two work packages (WP 3 & WP 4) had commercial focus and one work package (WP5) was dedicated to project management. In the following, for each of the work packages WP 1 – WP 4, the specific sub-goals as initially defined along with the project plan are shown.
Objectives and plan for WP1 – Industrialization of “ETZEL”
• Increasing stability and usability of the software in line with commercial requirements
• Set up SW verification and regression environment
• Validating the final hardware of ETZEL
• Set up calibration environment and implement calibration and burn-in tests
• Submit deliverables D1.1 “ETZEL Device” and D1.2 “ETZEL Documentation”
Objectives and plan for WP2 – Preparation for Market “DIMID”
• Execution of the RBC and WBC assay according to deliverable D2.1 “Validation Plan”
• Execution of the greenhouse and milk assay according to the validation plan
• Finalization of the DIMID haematology device to achieve demonstration level
• Finalization of the DIMID pollen analysis and dairy device in line with commercial requirements
• Integration of additional SW requirements into DIMIDSoft for the DIMID greenhouse and dairy device
• Submit deliverables D2.2 “DIMID Device” and D2.3 “DIMID Documentation”
Objectives and plan for WP3 – “DIMID” Commercialization and Marketing
• Define and submit the business plan D3.1 “Business Plan”.
• Deliver D3.2 “Patent Search”: Carefully monitor the risk of patent infringements.
• Submit deliverable D3.3 “Report on Scale-up and Supply Chain Management”: The DIMID and ETZEL contain several critical components, which require careful risk management of the supply chain.
• Submit deliverable D3.4 “Product Folder”: all marketing material need to be ready for the respective product launches, namely leaflets, brochures, specifications, advertisements and product web sites.
• Implement, test and document the web shop, submit deliverable D3.5 “Web Shop”.
Objectives and plan for WP4 – Trainings and Customer Demos
• Prepare training material and perform customer demonstrations
• Submit the deliverables D4.1 “Training Material” and D4.2 “Report on Customer Demos”
Project Results:
Results achieved under WP1 – Industrialization of “ETZEL”
Main focus of this work package was on the preparation of the market launch of the ETZEL measurement instrument. A major part of the staff of Zurich Instruments was working in parallel on creating marketing material, commercial ads, product user and programmers manuals and product videos. In parallel, the ETZEL hardware and software validation tasks were taking most of the attention. On the hardware side, two further design spins were required mainly with the focus on noise performance improvements. On the software side, there were three areas of focus, which were executed in close collaboration with the consortium partner LABS64: functional verification including setup of a complete regression environment, increased stability and improved usability. For the latter one, a graphical view of the main lock-in tab was added to the LabOne measurement software package. Other activities focused on the scale-up of the manufacturing and warehousing processes. The anticipated sales volume of the MFLI required the introduction of a company wide ERP system including the setup of a web shop. Both systems were defined, implemented and verified during the second period of the project. On January 30th, 2015, Zurich Instruments launched the ETZEL under the brand name MFLI to the market. All product is found under:
http://www.zhinst.com/products/mfli.
All deliverables of this work package were submitted on time, namely the ETZEL device and documentation.
D1.1 “ETZEL Device”:
For more information on the product, a short video is available under:
https://www.youtube.com/watch?feature=player_embedded&v=5ihQH0hCmr4
The new product is intended to become the new standard for lock-in amplifiers in the frequency range of up to 500 kHz challenging the current market leader, the SRS 830:
The MFLI product comes along with an outstanding tool set: LabOne.
D1.2: “ETZEL Documentation”
The MFLI comes with a detailed set of user documentation. For detailed information, please refer to:
http://www.zhinst.com/products/mfli.
Results achieved under WP2 – Preparation for Market “DIMID”
In work package two, the consortium partners CELLIX, AMPHASYS and CYTOGNOS worked in parallel on the market preparation for their products.
D2.1 “Assay Validation”
The main focus on CELLIX side was on the RBC and WBC haematology assay validation including creation of a draft project plan on how to achieve IVDD certification:
In parallel, the portable DIMIDplus haematology analyser was further integrated and brought to a stage where it can be deployed to potential OEM partners. First clinical tests with volunteers were setup. On January 29, CELLIX successfully demonstrated the DIMIDplus haematology device at the premises of Zurich Instruments in the context of a F2F consortium meeting. Blood of several volunteers of Zurich Instruments was measured demonstrating the performance of the device and assay including the analysis of cell populations with the DIMIDsoft provided by CYTOGNOS.
On the side of AMPHASYS, the key activities were related to the validation of the assays for pollen analysis and dairy food applications.
The first priority was on the successful launch of the pollen analysis assay. For the determination of pollen viability no standard method exists. Individual seed companies have developed their own protocols that rely basically on some published data and depend, of course, on the sort of pollen to analyse. Most seed companies have validated the AMPHASYS technology with their methods, but do not want to disclose the data.
However, analyses were performed at 0.5 and 12 MHz and compared with pollen stained with FDA/PI (Fluorescein Diacetate / Propidium Iodide), a fluorescence dye mixture that selectively reveals viable and dead cells by fluorescence microscopy. Pictures of the stained samples are taken, the green (DAPI, viable) and red (PI, dead) cell counted and the obtained ratios compared with the analyses performed with the DIMIDplus device. A very high correlation between both methods could be demonstrated.
Based on the excellent results, AMPHASYS successfully launched the DIMIDplus device for pollen analysis, named as AMPHA Z30 to the market in April 2014.
During the last 6 months of the project, AMPHASYS increased its focus on the milk assay. Several laboratories were contacted and the device was demonstrated to customers in Switzerland and France. The performance of the assay continuously improved and was finally benchmarked against traditional, optical based technologies. An evaluation of the technology was done with a prototype of the AMPHA Z30. Samples were measured at the facility of Amphasys and at Swissmilk (Zollikofen, CH). The data provided evidence of a good correlation between the DIMIDplus for somatic cell count on raw milk and the Fossomatic device, which is considered to be the gold standard.
D2.2 “DIMID Device”
During the DIMIDplus project, both CELLIX and AMPHASYS further improved their DIMID devices. Below the pictures are shown for the portable DIMID haematology analyser that is used as a demonstrator for potential OEM partners and the DIMID device for pollen analysis and dairy food applications.
D2.3 “DIMID Documentation”
This document was written in tight collaboration with CELLIX, AMPHASYS, ZURICH and CYTOGNOS. It contains three main sections, which are related to the DIMID device for haematology, the DIMID device for pollen and milk analysis and the DIMIDSoft impedance flow cytometry analysis software.
a) DIMIDplus Portable Device for Haematology
The documentation part for the DIMIDplus portable device for haematology has been made available and serves as a base for further steps towards final commercialization in collaboration with a potential OEM partner. In particular, it contains all information about the sub-systems of the device, the validation results of the RBC and WBC assays and a roadmap towards IVDD certification.
b) DIMIDplus Device for Pollen Analysis and Dairy Food Applications
The documentation part for the DIMIDplus device for pollen analysis and dairy food applications has been made available and serves as a base for manufacturing. In particular, it contains all information about the sub-systems of the device and the validation results of the pollen and milk assays.
c) DIMIDSoft Analysis Software for Impedance Flow Cytometry Data
The documentation part for the DIMIDSoft analysis software for impedance flow cytometry data has been made available. It describes an overview of the software architecture. Even if DIMIDSoft scope was not foreseen to pass a potential IVD certification audit, the ISO: 13485 and UNE: 62304 SOPs implemented at CYTOGNOS for software design and development would allow complying with IVD requirements rather straightforward.
Results achieved under WP3 – Commercialization and Marketing
The work performed in work package three included mainly the study of the relevant markets and the preparation of marketing material like product folders and videos and the scale-up for production ramp-up of the various devices.
All deliverables of this work package were submitted on time or with a minor delay.
D3.1 “Business Plan”
A detailed business plan was defined based on several market studies performed. A lot of emphasis was put on understanding the competitor landscape for the various technology offerings:
Competitive comparison haematology analyser market:
Company Cellix Samsung Abbott Horiba Sysmex
Device DIMIDplus
LabGeo HC10
Cell-Dyn Emerald
HHi 2K,en Derzlic
pocH-100i
Dimensions (HxWxD) 10.6” x 11.8” x5.9”
27 x 30 x 15(cm) 14.5” x 13.5” x 11.5”
39 x 34.4 x 29.3 (cm) 13.8” x 9.8” x 13.8”
13 x 25 x 35(cm) 16.5” x 14” x 12.5”
41.9 x 35.6 x 31.8 (cm) 7.3” x 13.8” x18.1”
18.5 x 35 x 46
Weight (lbs/kg) 5.5lbs / 2.5kg 28lbs / 12.8kg 20lbs / 9kg 31lbs / 14kg 30.8lbs / 14kg
List Price €6,000 / $8,000 €2,800 / $4,841 *Source: http://www.medicalequipmentcentre.com/
€22,000 / $30,000 €16,500 / $22,500 €13,200 / $18,000
Used N/A Unknown €3,700 – 5,900 / $5,000 €4,400 / $6,000 €1,800 / $2,500
Parameters RBC, WBC & WBC-3 diff. 18 parameters:
WBC-3 diff, WBC, LYM, MON, GRA, LYM%, MON%, GRA%, Hb, HCT, RBC, MCV, MCH, RDW, MCHC, PLT, PCT, MPV, PDW 18 parameters: WBC, RBC, Hb, Hct, MCV, MCH, MCHC, PLT, %&# neut, mono, lymph, eos, baso CBC Mode (16 parameters): WBC, RBC, HGB, HCT, MCV, RDW, MCH, MCHC, PLT, MPV,*PCT,*PDW, % and # of LYM, MON and GRA Whole blood mode: 17 parameters with 3-part Differential
Pre-dilute mode: 8 Parameters, which includes WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT
CV 3% WBC count
3% RBC count 1.6% WBC count
1.3% RBC count
0.8%Hb
3.3% platelet 3.5% WBC count
2.0% RBC count
2.1%Hb
6.1% platelet
1.7% Hct
0.8% MCV 2.5% WBC count
2.0% RBC count
1.5%Hb
5% platelet (WB or PLT concentrate)
2% Hct
Min Volume 25 µL 25 µL 9.8 µL 10 µL 15 µL
Time to result ~60 seconds 45 seconds
Sample type EDTA whole blood EDTA whole blood WB, PRP WB and pre-dilute
Throughput Unknown 80 samples / hr 60 samples / hr 60 samples / hr 25 samples / hr
The demand for haematology analysers is influenced by the development of alternative technologies such as point-of-care (POC) instruments and integrated analysers, advancements in product automation and highly streamlined lab processes. Cell analysers presently available for lab purpose are multi-channelled, as they analyse various haematology measurements utilizing diverse techniques. A number of patients prefer home monitoring devices.
Developing products by integrating complementary technologies such as imaging, software, HT and multiplexing in compact bench top flow cytometers, which may target POC markets can help market players gain a substantial boost in sales. Existing players have already started considering the importance of automation and sample handling; however, there is still a lot of scope in this space, as developing flow cytometers with integrated sample automation can save costs significantly by reducing the amount of sample volume and offering HT. Also, automation can enable rapid data exchange across different systems. With increasing focus on the need for HT, there would also be a continuous need for advanced software that can analyse and manage the large amount of data generated. Thus the market players can tap this opportunity. The DIMIDplus haematology device is a small, portable, low-cost system, which can target applications in point-of-care settings such as:
• Emergency rooms where devices may need to be moved to the patient bed-site
• Mobile first responders including air and ground ambulances
• Remote medical centres or satellite hospitals.
• Doctor’s office
The attractiveness of the compact footprint of the DIMIDplus device was echoed during interviews with key stakeholders. Further benefits of the DIMIDplus haematology device include leveraging the microfluidic nature of the device thereby enabling the targeting of specific patients such as neonates and children where typical blood volumes are in the region of 1-4mL.
Going forward, the global market for in vitro diagnostic products will remain captive to the growing and significant financial challenges facing health care delivery systems as population age and underserved populations demand improved care. The advent of Obamacare in the US is expected to particularly constrain service and product pricing in that nation as the delivery system attempts to accommodate significantly more patients, many of whom have the expensive “triad” of diseases – obesity, diabetes, and hypertension. Other developed nations will also be coping with aging, sicker populations, pushing their health delivery systems to the limits. For these reasons, health care systems and players are looking for disruptive technologies that significantly reduce costs, significantly improve health care or preferably do both. This will raise the bar for companies seeking to develop blockbuster products, as technologies that offer incremental improvements will not see broad application.
On the risk side to enter these markets, the regulatory constraints need to be well understood. In Europe, the Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices and successive amendments and corrections, aims at creating a single market and reducing technical barriers to trade for medical devices. It introduces common regulatory requirements for IVDs across Europe, bringing IVDs in line with other medical devices. The Directive lays down harmonising rules designed on the safety, quality and performance of IVDs. In the USA, the procedure on how to market a diagnostic device is well explained on the FDA website:
http://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/default.htm
Comparative comparison milk analysis:
The quality of milk is among others assessed by counting the number of bacterial and somatic cells. Current analytical instruments are too complex and expensive (instruments and assay costs) for most dairy food producers. Therefore, thousands of samples are screened daily by simple qualitative tests, which occasionally fail causing costly production losses.
Ampha Z30 represents a low-cost, easy-to-use device that can be used for both bacterial and somatic cell counting. So far, there is no solution on the market for a simultaneous count of bacterial and somatic cells. Amphasys’ technology could fill that gap and achieve a comfortable position if the analysis is possible directly on raw milk. In the course of the DIMIDplus project, this was successfully demonstrated.
In contrast to the haematology market described above, somatic and bacterial cell counting of raw milk is not subjected to severe regulatory norms. The qualification of the product quality, however, is clearly defined and regulated, which means that cell counters do need to fulfil counting precision and accuracy criteria for being used in the qualification process. The technology must therefore prove to meet the specifications of the established and accepted analysers (from FOSS or Bentley Instruments), which will require regular calibrations and validations of the systems.
The development of a specific sales force for the milk analysis application seems not to be the optimal choice for penetrating the market. Partnering with one of the larger companies (FOSS, for example) as an OEM supplier would provide a much faster access to this large market.
Comparative comparison pollen analysis:
Presently, the only alternative to determine pollen viability is either using fluorescent dyes and counting the cells with microscopes, or performing germination assays, which however take a lot of time. Amphasys’ impedance flow cytometer will clearly fill this technological gap. The table below lists current technologies used and compares it with Amphasys’ solution.
Technology Impedance Flow Cytometry Fluorescence microscopy In vitro germination
Device Ampha Z30 Fluorescence Microscope Petri dish
Throughput 20 analyses / h 6 analyses / h 100 analyses / day
Reproducibility High Low Low
Analysed cells / test 10’000-50’000 < 50 < 50
Reliability High Low Low
Specificity towards pollen types Low High High
Suitability for greenhouse Yes No Not effective
Portability Yes No Yes
(A) Pollination results expectedly in no fruits at all. (B) Correlation between measured pollen viability and production of embryos, which generate new plants. (C) Typical seed setting curve for tomato resulting from pollen viability analysis with Amphasys’ device.
D3.2 “Paten Search”
The patent search was executed by CELLIX with support of AMPHASYS. The study was executed taking into account the key objectives of the DIMIDplus project and subsequently distributed to the DIMIDplus consortium in order to avoid possible patent infringements. This study acted as well as an aid for the consortium to define an appropriate IPR protection strategy.
D3.3 “Report on Scale-Up and Supply Chain Management”
The work on a scale up concepts and basic supply chains for all three products resulting out of DIMIDplus has been reported in D3.3 “Report on Scale Up and SC Status”. The DIMIDplus Consortium has a highly interlinked supply chain strategy with strong mutual dependencies.
All partners have performed a detailed risk assessment creating awareness of their supply chain dependencies and how this might impact their ramp-up schedule. Where possible, a second source supplier has been defined. However, this was not feasible for all critical parts of the respective products.
In order to mitigate those risks, the partners are currently negotiating OEM respectively license agreements for critical parts that have no obvious alternative for second source supply.
D3.4 “Product Folder”
All partners developed marketing material for their respective products. Below a small excerpt of the respective product folders:
Product Folder MFLI:
Product Folder DIMID device for haematology:
Product Folder AMPHA Z30:
Product Folder DIMIDSoft:
For further information, please refer to the relevant product pages:
• http://www.zhinst.com/products/mfli
• http://cellixltd.com/products
• http://www.amphasys.com/impedance-flow-cytometry
• http://www.cytognos.com/dimidsoft
D3.5 “Web Shop”
The MFLI is the third product platform of ZURICH and covers the frequency range of 50 kHz to 5 MHz. It has been launched to the market January 30th, 2015 under the brand name MFLI. The MFLI platform has the potential to reach a sales volume of 1000 units per year by end of 2018.
This strong growth requires dedicated strategies, which target on:
• Efficiency of the pre-sales, sales and post-sales processes including provision of a webshop
• Efficiency and scale-up of the supply chain including manufacturing and warehousing
As a consequence, ZURICH decided to define an IT Integration strategy, which has been implemented and is reflected in the deliverables D3.3 “Report on Scale-Up and SCM” and D3.5 “Webshop”.
At the end of the DIMIDplus project, two essential elements of this strategy are now available: the Webshop and the ERP manufacturing and warehouse modules.
With those two elements in place, ZURICH is prepared to successfully execute the manufacturing, warehousing and sales processes for up to 1000 MFLI units per year.
At the time of taking the screen shots, the webshop was still undergoing tests and was hosted on a test environment: ziweb2/deploy/droducts/mfli (the test environment is not visible to the outside world)
Results achieved under WP4 – Training and Customer Demos
This work package only started in project period two. Apart from LABS64, who are not planning to deploy a commercial product within the scope of DIMIDplus, all consortium partners prepared and executed several trainings and customer demos.
This work is documented in detail within the deliverables “Training Material” and “Report on Customer Demos”. Leaflets, user manuals and application notes can be found as well on the respective home pages of the partners. Both deliverables of this work package were submitted on time or with a minor delay.
D4.1 “Training Material”
All training material required to conduct trainings and to perform customer demos has been made available. The deliverable D4.1 “Training Material” has been submitted in Month 16 with a delay of one month. Although this deliverable has been submitted, new training material is constantly being generated.
The table bellows shows a summary of the training material that has been made available:
ZURICH CELLIX AMPHASYS CYTOGNOS
Technical Specifications Technical Specifications AmphaZ30 User Manual Technical Specifications
Quick Start Guide Videos AmphSoft User Manual User Manual
Tutorials Quick Start Guide
Functional Description Webinars
Programmer Manual
Application Notes
Videos
D4.2 “Report on Customer Demos”
The product launches of the ETZEL under the brand name MFLI and the DIMID device for pollen analysis under the brand name AMPHA Z30 occurred in January 2015 and April 2014, respectively. For both products, ZURICH and AMPHASYS did numerous customer demonstrations, either during product fairs or directly on-site with customers. For the DIMID device for milk analysis, AMPHASYS did so far one demonstration. More customer demonstrations will follow in the second half of 2015. On CELLIX side, the focus in the second period was still on assay validation. Results of the validation stage were presented to numerous potential OEM partners, but so far on slides only. Demonstrations with the actual device are planned to occur in the second half of 2015. CYTOGNOS demonstrated DIMIDSoft so far only to Consortium internal stakeholders.
Results achieved under WP5 – Project Management
The project management main focus was on tracking the overall progress of the project towards the end of the period. The critical path towards the end goals of the project was constantly monitored and optimized by frequent Skype calls, and where required, by F2F meetings. On top of this, a common platform for information sharing was installed (Confluence). Work shared between partners was tracked and documented there.
While some of the project tasks could be executed quite independently by the individual partners some other tasks required very close alignment and task interfaces between partners had to be carefully reviewed and constantly optimized. Most challenging was the final integration of the product components provided by ZURICH, AMPHASYS and CYTOGNOS into the final version of the DIMIDplus haematology of CELLIX. For this reasons, dedicated handover Skype calls were organized, in particular between CELLIX and ZURICH. A final handover of the ETZEL electronic unit to CELLIX was successfully performed beginning of November 2014 during a handover and training session taking place in Dublin.
During the second period of the project, more and more focus was put on exploitation and on dissemination, which is reflected in the list of deliverables below. All deliverables of this work package were submitted on time without any delay.
D5.1 “Consortium Agreement”
The Consortium Agreement was negotiated at the very beginning of the DIMIDplus project and signed by all partners in December 2013.
D5.2 “Draft PUDK and D5.3 Final PUDK”
Dissemination of knowledge of projects funded under the FP 7 is an obligation, but also an opportunity to increase the expected impact and visibility of the project outcome. For a demonstration project such as DIMIDplus, where final products ready to be marketed are the expected outcome, dissemination activities are even more important than in R&D projects. WP3 Commercialization and Marketing and WP4 Training and Customer demos of the present project are already including major dissemination activities and are therefore just briefly mentioned in this deliverable. Besides those, the deliverable contains an IP strategy followed in this project.
D5.4 “Exploitation Agreement”
One of the key deliverables of project management during the second period of the project was to negotiate and finalize the exploitation agreements among all partners. IP and OEM partnership agreements not detailed in the Consortium Agreement had to be clarified and resulted in complementing exploitation agreements.
Potential Impact:
The DIMIDplus project has bridged the gap between research and market by investing a joint effort of five SMEs to commercialize a high-tech, high-potential technology. The consortium has formed a highly linked business model focussing on six business opportunities:
During the DIMIDplus project, the five partners have further built and strengthened their core competences:
In the following section, the achieved commercial results of all SME and the wider impact are summarized:
Commercialization Opportunity 1: ZURICH – Physics Research
The ETZEL has been commercialized and launched under the name MFLI as instrument dedicated to Physics Research on January 30, 2015. The product can be found and ordered under http://www.zhinst.com/products/mfli. The MFLI sets the new standard for measurements in the medium and low frequency range and is available in two versions: DC to 500 kHz and DC to 5 MHz (an upgrade from 500 kHz to 5 MHz is possible later). The MFLI combines superior performance with the outstanding LabOne® toolset. The embedded data and web servers allow straightforward connection to any device running a web browser.
Typical Physics applications are:
• Optical chopper applications
• Pulsed laser applications (e.g. high power lasers)
• Materials research
• Quantum- and Nano-electronics
• Materials research
• Scanning tunnelling microscopy
• Low temperature physics
• Impedance spectroscopy
• Seismic measurements
Commercialization Opportunity 2: ZURICH – Biology Engineering and Research
The MFLI is commercially available and can be purchased in a 5 MHz and a 500 kHz version. Customers that initially purchased a 500 kHz version can upgrade their device later to 5 MHz by purchasing the MF-F5M frequency extension option. Furthermore, a MF-MD multi-demodulator option is available. Both options together turn the MFLI into a powerful instrument for impedance spectroscopy serving the biology engineering and research markets.
Socio-economic Impact and wider societal implications (Opportunity 1 & 2):
• Creation of 15 job opportunities directly at Zurich Instruments within the next 3 years
• Creation of up to 25 job opportunities with suppliers of Zurich Instruments within the next 5 years
Dissemination Activities (see Annex for more details)::
• Strong representation at several exhibitions during the product launch in February and March 2015
• Press releases
• Videos
Exploitation Results (see Annex for more details):
• Two commercially available products MFLI 500 kHz and MFLI 5 MHz.
• LabOne measurement software, trademark submitted and registered in September 2014.
Commercialization Opportunity 3: AMPHASYS – Seed and Pollen Analysis
The AMPHA Z30 is commercially available and can be purchased under http://www.amphasys.com. This instrument is being used for many research applications like bacterial analysis, apoptosis or cell differentiation (cancer and stem cell research) as an alternative to conventional, fluorescence-based flow cytometers. Besides the classical research applications, AMPHASYS is also focusing its activities on industrial applications, where the company sees a huge potential for the technology.
The reliable determination of pollen quality is a key success factor in the seed production process. Experiments show a clear correlation between the viability (also called vitality) of pollen used for pollination and the obtained seed yield. External factors such as light, rain, temperature or chemical agents may influence pollen viability. Amphasys provides an easy method to monitor pollen viability and thus a powerful tool to optimize the plant breeding and seed production process. This is particularly important if laborious manual steps are involved and if pollen needs to be stored or transported from one site to another. The technology can be used on-site, directly in or near the greenhouse.
The product has been launched in April 2014. AMPHASYS has received several orders and is shipping the device to customers.
Commercialization Opportunity 4: AMPHASYS – Dairy
For the milk industry, the quality of raw milk is a major concern. High somatic cell counts mainly caused by bacterial infections and bacterial contamination caused by insufficient equipment sanitation or insufficient cleansing of the cow's udder and teats have an adverse impact on the milk products. Amphasys’ technology allows a direct determination of the somatic cell count in untreated raw milk. The product will be launched in the second half of 2015. AMPHASYS is in contact with several customers interested in the dairy application and first orders are likely to materialize in the end of 2015.
Socio-economic Impact and wider societal implications (Opportunity 3 & 4):
• Creation of several job opportunities directly at AMPHASYS and as well at their suppliers
• Increased efficiency of seed and crop production through availability of a new technology that can reliably measure pollen viability
• Improved herd management for farmers by efficient and cost effective monitoring of the somatic cell count of raw milk
Dissemination Activities (see Annex for more details):
• Press releases
• Conferences
• Videos
Exploitation Results (see Annex for more details):
• Commercially available product AMPHA Z30
• Single cell analysis software AMPHAsoft
Commercialization Opportunity 5: CELLIX - Non-IVD Haematology applications
The DIMIDplus portable device for haematology may be marketed to the non-IVD scientific research market. This business case has not been actively pursued within the DIMIDplus, but remains a valid business option.
Commercialization Opportunity 6: CELLIX - Haematology diagnostics (OEM)
The DIMIDplus portable device for haematology diagnostics is available for demonstration to research customers and potential OEM partners. Due to its complexity, this commercialization opportunity has received the highest attention within the Consortium, as it required the close cooperation of all partners. CELLIX has entered negotiations on deploying the new technology to several diagnostics partners.
Socio-economic Impact and wider societal implications (Opportunity 6):
• Strongly depending of future collaboration with potential OEM partners
• Full scale-up and commercialization of a portable point-of-care device will create a significant number of job opportunities at CELLIX itself, at its OEM partner and at the corresponding suppliers
• The cost advantage over traditional optical based haematology analysers combined with the portability of the device can have a significant impact on personal health coverage for emerging markets and regions with reduced access to hospitals.
Dissemination Activities (see Annex for more details):
• Presentation of the technology at various conferences, e.g. uTAS in Texas, October 2014.
• Videos
Exploitation Results (see Annex for more details):
• Available demonstrator for haematology diagnostic applications targeting RBC and WBC assays
List of Websites:
The DIMIDplus Website has been continuously updated during the project including a new front page with images for pollen and dairy applications, new videos, updated partner’s events participation, press releases and news. Following the EC recommendations FP 7th logo has been substituted by the EU emblem on the DIMIDplus website.
The website maintains a simple and clear structure presenting the outcomes of the DIMIDplus project and the future marketable products. During the entire project, new DIMIDplus brochure, posters and logo have been created with a new refreshing aspect focused on benefits and broad potential applications of the impedance flow cytometry. DIMIDplus brochure and posters are available at the home page.
Contacts of the project partners are listed below:
ZURICH INSTRUMENTS AG Coordinator • Adrian Messmer, VP R&D
• Email: adrian.messmer@zhinst.com
CELLIX LIMITED Partner • Vivienne Williams, CEO
Email: v.williams@cellixltd.com
CYTOGNOS SL Partner • Álvaro Rodríguez, CFO
Email: alrodriguez@cytognos.com
AMPHASYS AG Partner • Marco Di Berardino, Executive Partner
• Email: marco.diberardino@amphasys.com
LABS64 GMBH Partner • Konstantin Korotkov, CEO
• Email: konstantin.korotkov@labs64.de
