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Biopsy equivalent Optical Fiber multifunctional Endoscope

Periodic Reporting for period 2 - BiOp-FibEnd (Biopsy equivalent Optical Fiber multifunctional Endoscope)

Reporting period: 2018-06-01 to 2019-05-31

Suspect body cavity tissues are currently investigated, in-vivo, by endoscopy. Endoscopy relies on visual identification of potential problematic areas by the judgement of a trained clinician to determine whether the investigated tissue is healthy. If further investigation is needed, part of the tissue is removed and sent to laboratories for a biopsy. This entire procedure relies on subjective judgment and has delayed diagnosis. The implications of it span between an incorrect diagnosis, unnecessary psychological pressure on the patients and high costs to the system because of the need of repeated examinations.
The project aims at realizing tools that can help reduce the risk of mistakes and the costs of healthcare, and obtain quicker diagnosis, reducing the stress factors related to such investigations. In particular, this is done by combining spectroscopy to obtain information on the composition of tissues together with imaging techniques.
The project is separated in 3 parts:
- The first part is the realization of metamaterial lenses working in the mid-IR. Such lenses would allow to use longer wavelengths, beneficial for spectroscopy, without compromising imaging resolution.
- The second part is the realization of endoscopes for imaging and spectroscopy to carry the information from inside to outside the body.
- The third part is to include depth imaging information by mid-IR Optical Coherence Tomography (OCT).
Most of the tasks planned were successfully carried out, advancing the knowledge and the state of the art considerably. The action allowed wide scientific dissemination of the results obtained and assisted to the future commercial potential of some of the devices investigated in the field of health care management and prevention. The action also created a great opportunity for the investigator in terms of network, professional and personal growth.
The fabrication of metamaterial hyperlenses for the mid-IR required multimaterial drawing of small and non-trivial structures. In particular, dielectric structures including as many as 500 metallic components, with features as small as 150 nm were realized. The fabrication was not limited to wire-array structures, but also spanned to resonators arrays, covering both the key elements for metamaterials. Other aspects of fabricating hyperlenses were investigated: tapering, handling, polishing, gluing. Following the understanding and implementation of the fabrication process, the optical performances of the hyperlenses were characterized. The first step was to test the devices at THz frequencies, where these lenses have less stringent requirements, but covering anyway a very interesting domain for spectroscopy. In this regime, imaging below the diffraction limit to resolution 13 times lower than the wavelength and focusing to a spot 176 times smaller than the wavelength were achieved. Also, a simplified magnifying hyperlens structure -a prism instead of a taper– was investigated both theoretically and experimentally. imaging with the hyperlenses in the mid-IR was demonstrated.
The second part of the project focused on endoscopes for the mid-IR, with interest more in new materials than new structures. There are well known glasses that can be used for transmission in the mid-IR. However, most of the contain arsenic, which is not ideal for medical applications. Two approaches to this problem were implemented. The first was to look for an arsenic-free glass with similar transmission and fabricate devices with such glass. The glass chosen is commercially known as IG5. The fabrication process for fibers made with such glass was successfully developed. The second approach followed was that to find a more biocompatible material compared to the IG5 glass. To this purpose, an elastic polymer was used to fabricate optical fibers for the first time, polyurethane. This polymer is already largely used in medical devices. The mechanical properties of such material allowed to also realize tunable metamaterials, to create waveguides that allow radiation manipulation and to realize very sensitive pressure sensor. From the spectroscopy point of view, a system for tissue recognition based on visible light spectroscopy and neural network data analysis was developed.
Following up from the other developments of the projects and keeping in line with the action objectives of providing tools to improve health investigation and reduce the costs of health care, the investigation of a system to monitor blood pressure continuously was performed. Moreover, the ability of fabricating biocompatible fibers was exploited to start a project on cell growth for tissue regeneration.

The project outcomes resulted in, so far, 12 journal articles published, 2 submitted patent applications, and 38 conference presentations.
Overview of the main results:
- Realization of glass fibers with up to 500 metal wire inclusions of size down to 150 nm; realization of metallic slotted cylinder resonator array in a glass matrix; realization of a soft/hard polymer fiber with metal inclusions for metamaterials with 50% tunability. Published in 4 journal articles and presented at more than 20 conferences.
- The process to realize structured fibers with polyurethane and polycaprolactone (biocompatible polymers for medical applications) using the fiber drawing technique was investigated for the first time. A patent application is filed, presented in more than 10 conferences.
- An arsenic free glass was investigated for operation in the mid-Infrared, a theoretical model to aid the fabrication was implemented and microstructured fibers out of such material were fabricated. Published in a journal article and presented in 4 conferences.
- The fabricated structures were used to demonstrate imaging 13X below and focusing 176X the diffraction limit. Published in 4 journal articles and presented in more than 20 international conferences.
- Polyurethane fibers were used to realize sensors that can be included into wearables: to monitor breathing during walking and running; and to measure the pulse wave velocity, which relates to blood pressure. Presented at 7 conferences, a patent application is filed.
- A fiber bundle was used to realize a catheter for recognition of the heart tissue during ablation surgery combined with artificial intelligence.
- Polyurethane was used to demonstrate generation of orbital angular momentum modes at THz frequency in a reversible manner. Published in a journal article and presented at 3 conferences.
The new fabrication procedures and materials developed within the project will see large use in the fields of metamaterials, multifunctional fibers, mid- IR applications and medical devices. The project will continue such development with an eye on potential commercialization of devices by its end.
The largest contribution is expected to be given in the field of smart fabrics and medical devices. The novel type of fibers realized have the ideal mechanical properties and show both optical and electrical functionalities, which are key to the realization of devices that can “feel” and interact with the environment around them. Moreover, they have mechanical properties closely matching to human tissues and therefore are ideal for devices to be worn or integrated in the body. Such devices have been patented during the action and prototypes will be readily available for testing in the near future.