V I A M O S
Vertically Integrated Array-type Mirau-based Oct System
for early detection of skin pathologies


Seven Framework programme : Small and Medium-scale focused research projects (STREPs)
Call FP7-ICT-2011-8
Biophotonics for early, fast and reliable medical diagnosis of diseases.




1st October 2012-31st may 2016
Grant agreement no.: 318542

Coordinator : Prof. Christophe Gorecki
FEMTO-ST - Université de Franche-Comté (UFC-P5)
christophe.gorecki@univ-fcomte.fr - +33 381666607

Administrative Contact : Laura Pflüger
EU Affairs Manager
SAIC - Université de Franche-Comté
laura.pfluger@univ-fcomte.fr - + 33 381665814


INTRODUCTION

  Skin cancer is the most commonly diagnosed type of cancer. Its early diagnosis is essential since it can be treated more effectively when detected earlier. Visual inspection followed by histological examination is, still today, the gold standard for clinicians. However, a large number of unnecessary surgical procedures are still performed.

  New diagnostics aids are emerging including the recent techniques of optical coherence tomography (OCT) which permits non-invasive 3D optical biopsies of skin, improving patient’s quality of life. Nevertheless, the existing bulk systems are expensive, only affordable for hospitals and thus, not sufficiently used by physicians or dermatologists as an early diagnosis tool.

  The goal of VIAMOS is to benefit from advanced MOEMS technologies, enabling a new generation of miniature instruments. The challenge is to provide hand-held, low-cost, fully parallel spectral domain miniature OCT devices (10x cheaper, 150x smaller), adapted for early diagnosis of cutaneous pathologies. VIAMOS will lean on the experience and results fostered from a previous European collaborative project, diffusing the technology to medical diagnostic applications. The consequence will be a significant upgrade by adding new features such as heterodyne detection and integrated swept source.

  Thanks to its ability to deliver high-resolution 3D topography of skin with multifunctional modules (e.g. polarization sensitive cartography), VIAMOS will propose an OCT microsystem able to revolutionize the field of microscopes for dermatology imaging.

  To achieve these objectives, VIAMOS brings together an experienced consortium made of 2 academic institutions (Université de Franche-Comté, University of Stuttgart), 3 research institutes (VTT of Finland, Fraunhofer Institute ENAS, CSEM) and 2 industrials (DermoScan GmbH, Statice SAS), covering MEMS & MOEMS, photonics & OCT, microscopy, system integration and dermatology. A unique team of transverse expertise is gathered in VIAMOS to design and demonstrate a miniature solution for in vivo 3D skin imaging to further address the early diagnosis of cutaneous pathologies that will potentially benefit millions of people worldwide.

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Scientific and technological challenges

  VIAMOS proposes a miniature, low cost, 3D OCT imager combining swept-source OCT detection and MOEMS technologies, providing cross-sectional 3-D tomograms with a depth greater than 0.5 mm, axial and transverse resolutions of 5 µm and imaging field of 10x10 mm2. VIAMOS capitalizes on the SMARTIEHS collaborative project results that will be significantly upgraded by addition of heterodyne detection with on-chip Mirau interferometry and integrated micromachined swept-source. To validate the technical and functional performances of VIAMOS microsystem, series of translational trials will be performed at the Besançon University Hospital. This study will consider melanoma and non-melanoma skin cancers (namely basal cell carcinoma) as well as non-cancerous skin lesions.


State-of-the-art

  Non-melanoma skin cancer including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common form of skin cancers and the most commonly occurring cancers in the world. BCC and SCC have substantially better prognoses than more aggressive melanomas. Melanoma is one of the most important cancers in terms of “years of potential life lost per death”. In 2000, approximately 50 0000 people were melanoma-diagnosed in Europe, and around 16 000 people died of their disease. Nowadays, the main proposed screening procedure is the visual examination of the skin, including both clinical examinations and self-examinations. Traditional biopsy is still today the reference technique of diagnosis. Nevertheless, biopsy suffers from several drawbacks, such as a long diagnosis time and invasiveness. Consequently, non-invasive imaging methods have been employed for clinical use, including ultrasounds, computed tomography and magnetic resonance imaging. However, the resolutions of these techniques are of the order of 100-200 µm, what is enough to identify large features, but not sufficient to resolve the morphology of individual cells which are normally 5 to 10 µm in size. The confocal microscopy presents the advantage of high resolution (1 µm) but suffers from a relatively low depth of penetration (100-200 µm) which is not enough to image the epidermis and the dermis where most developed cutaneous lesions may take place.

  Optical coherence tomography (OCT) is a more recent (1991) non-invasive imaging technique based on low coherence interferometry. The resolution can reach 3 to 15 µm and the skin penetration depth may reach 1 mm which is very well suited to morphological imaging of diffusive media. In consequence, OCT is a perfect trade-off between ultrasound and confocal microscopy. The point-scanning nature of OCT technology allows it to be implemented in fibre optics, which makes endoscopic and catheter-based imaging possible. By using the time-delay reflected light from different depths inside a sample, OCT can reconstruct a depth-profile of the sample media. 3D images can then be created by scanning the light beam laterally across the sample surface. Whereas the lateral resolution is determined by the size of the focal point of light source, the axial resolution depends primarily on the optical bandwidth of the laser source. Thus, OCT systems may combine high axial resolutions with large depths of field. Starting from white-light interferometry for in vivo imaging of the human eye, OCT was investigated by a wide number of groups worldwide. First in vivo OCT images – displaying retinal structures – were published by Fujimoto group in 1993.  More recent implementations of OCT, namely the spectral domain (or frequency domain) OCT, provides advantages in sensitivity (which can reach 120 dB), and allows faster signal acquisition. The technique has already become established as a standard imaging modality for biological tissues, with numerous commercial instruments on the market. Figure 1 shows the recent evolution of applications of OCT to various medical areas such as ophthalmology, endoscopic imaging of gastroenterology, dermatology or cardiology, etc...

oct joseph izatt citations in web of science
Fig. 1. Recent evolution of OCT applications.

  Today, the maturity of MEMS and microoptical technologies start to be useful in the deep miniaturization of OCT systems. Our vision is matching this trend and is even converging towards the full integration of compact, handheld and affordable, OCT systems. 3D packaging methods are appropriate for stacking various heterogeneous wafers in a minimum of volume.


Technological breakthrough introduced by VIAMOS

  Today, the conventional OCT microscopes are bulky, performing micro-scale measurements from the macro-world. The confocal microscopes  (see Figure 2), available on the market and used currently for  skin inspection  are bulky, using macro-parts : their volume is typically 3000 cm3 and the unit costs around 100 k€.

  The potential of MEMS and microoptical technologies, exploited by VIAMOS, will open the possibility to perform similar instrumental tasks in a hand-held instrument. Thus, decimetre-scale head of an OCT microscope will be shrunk to a millimetre-scale instrument, performing measurements with an equivalent lateral resolution. OCT microsystem, composed from arrayed elementary local sensors, will perform massively parallel and multi-functional measurements with 5-µm lateral resolution offered by interferometry.

Fig. 2. Confocal microscope at University Hospital, Besançon,
applied for clinical imaging of the skin.
Fig. 3. How to reduce the “top-down” effect by 3 orders of magnitude
in optical instrumentation.

VIAMOS’s approach is a breakthrough in OCT microscopy and will enable cheaper, portable OCT microsystem for early diagnosis of skin cancer, addressing the following issues :
  • an instrument 150 x smaller than a standard OCT system,
  • 10 x cheaper at least
  • a batch-fabrication concept
  • multi-functional instrument performing massively parallel inspection
  • high resolution 3D reconstructions of skin
  Most of all, this approach will improve the quality of care for patient not only with the suppression  of unnecessary painful surgery, but also with a drastic reduction in diagnosis time since the equipment will be affordable at the Point of Care.


Image Gallery

Some recent realizations of VIAMOS Partners


High-speed CMOS imager and camera with up to 8000 frames/second
(Partner CSEM SA)
.

Multilayer wafer bonding technology for reliable and
vertical integration of complex micro systems
(Partner ENAS/Fraunhofer)

Histological image : superficial spreading melanoma with
tumour thickness 0.3 mm and magnification x100 (Partner SMP/UFC-P5)

LCSI Image caption: line wise parallel acquisition of topography
by laterally chromatically dispersed spectral interferometry
(Partner USTUTT)

MEMS Fabry Perot Interferometer for spectrometry
(Partner VTT)

Series of parallel plate electrostatic microactuators with integrated ball microlenses for on-chip confocal microscope (Partner FEMTO-ST/UPC-P5)


Achievements of the first period of project (month 1 to month 19 months)

During the first period of VIAMOS proposal, the Consortium has focused on the system design, taking into account all the different technological constraints to be compliant with medical requirements. First basic blocks are under developments such as MEMS filter, out of plane actuator, microlens array, high speed camera and electronics. Design of assembly and packaging started.


Design: layout of the VIAMOS microsystem (USTUTT).

Glass microlens wafer for Mirau interferometer (FEMTO/UFC).

Glass platform wafer with reference mirrors carried by Z-scanner (FEMTO/UFC).

Sketch and SEM image of a 5 bonding-stack demonstrator (FhG).

Control electronics of the OCT system (VTT).

3-D view of the application board (top) and GTM board (bottom) to interface the test chip high-speed image sensor (CSEM).


Achievements of the second period of project (month 20 to month 44)

During the second period of VIAMOS proposal, the Consortium has focused on the assembly and packaging of complete OCT microsystem as well as the utilization in dermatology.


Matrix of glass lens doublets of VIAMOS microsystem (FEMTO-ST/UFC)

Vertical scanner with reference mirrors of Mirau interferometer of VIAMOS microsystem (FEMTO-ST/UFC)

Top view of assembled Mirau interferometer (FEMTO-ST/UFC)

Bottom view of assembled Mirau interferometer (FEMTO-ST/UFC)

3D image of an onion with OCT proof-of-concept bulk prototype (ITO/Uni Stuttgart)

Final camera of VIAMOS microsystem (CSEM)

Assembled view of complete VIAMOS microsystem (Statice)

OCT image of a paint sample with a varnish layer by VIAMOS microsystem sensibility 80 dB (FEMTO-ST/UFC)

Comparison of OCT image of keratosis pathology (commercial OCT) with histopathology image (SPM/UFC & CHRU St Etienne)
 

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