Miniature Mirau interferometry for swept-source OCT imaging with applications in dermatology

Transcription

1 Miniature Mirau interferometry for swept-source OCT imaging with applications in dermatology C. Gorecki 1, S. Bargiel 1, J. Lullin 1,, J. Albero 1, N. Passilly 1, S. Perrin 1, L. Froehly 1, W.- S. Wang 2, M. Wiemer 2 1 MN2S Department, FEMTO-ST, Besançon, France 2 Fraunhofer Institute for Electronic Nanosystems, Chemnitz, Germany christophe.gorecki@femto-st.fr

2 FEMTO-ST Institute: who we are? Besançon, TEMIS Sciences) Belfort & Montbéliard Transportation, Energy Microtechniques Besançon VIAMOS building blocks FEMTO-ST building) Research Institute created in people including: 320 permanent, 220 PhD students Largest Research Lab in Engineering Sciences in France 7 scientific Departments 1 MicroNanofabrication Center (MIMENTO): 865 m2 of clean room (class 100, 1000, 10000) 20 spin-offs created MicroNanofab Center

3 Summary Introduction: the challenges of OCT technology Design and vertical integration approach with VIAMOS FP7 project VIAMOS microsystem technologies and results Conclusion and perspectives

4 Miniature microscopes for autodiagnosis Lens-free microscope from UCLA Smartphone-based microscopes: examinations of tissues or cells, blood and other biological specimens CellScope: a phone microscope from UC Berkeley (X50) CellScope Convent. microscope Portable iphonemicroscope from TechCyn (x60) Handheld digital microscope Dino Lite4 (x200)

5 Medical applications of Optical Coherence Tomography OCT situation Medical market for full-field OCT systems Bulk systems: Zeiss Meditec Cirrus HD-OCT AGFA HealthCare: SKINTELL Michelson Diagnostics Etc.. In-vivo high cost systems: k Bulk microscopes only accessible at the Hospital or Clinic difficulty to perform the early diagnosis of skin pathologies

6 The VIAMOS consortium: 7 Partners Vertically Integrated Array-type Mirau-based OCT System for early diagnostics of skin pathologies Project budget 4.7M 7 European Partners 6

7 Dermatology: a challenge for OCT Skin cancer is by far the most common of all cancers Gold standard for clinicians: low resolution visual inspection followed by an histological examination Problems: a large number of unnecessary surgical procedures are still performed dermatologists do multiple biopsies to diagnosis the skin lesion Currently lack of high resolution instruments at low cost Correlation with histology

8 OCT : two categories of tomographs wide spectrum source Time domain OCT axial scan reference mirror detector X-junction Signal processing sample wide spectrum source Spectral domain OCT reference fixed arm mirror Grating spectrometer X-junction sample spatial demultiplexing TF

9 OCT : two categories of tomographs wide spectrum source Time domain OCT axial scan reference mirror detector X-junction Signal processing sample λ tunable source Swept-source OCT X-junction reference fixed arm miroir Smart camera sample temporal demultiplexing TF

10 VIAMOS OCT microsystem architecture Miniature, 3D OCT imager combining SS-source OCT detection, an array of Mirau interferometers in MOEMS technologies, a detection block with camera and a stitching actuator insuring the continuous scan of the skin sample. Mirau interferometer VIAMOS imager

11 MM fiber Array of active Mirau interferometers λ Mirror term Swept-source condenser beam splitter The motion of Mirau reference mirrors permits the operation of phase modulation with acquisition of 4 spectral interferograms skin Mirau doublet

12 MM fiber Acquisition of phase-modulated spectral interferograms λ OCT + phase modulation Swept-source condenser beam splitter Effect of phase modulation: filtering of «mirror-term» with extraction of phase and amplitude data with improved S/N ratio Mirau doublet skin

13 VIAMOS microsystem vs. commercial bulk OCT systems for the dermatology Michelson Diagnostic AGFA HealthCare VIAMOS Position of VIAMOS VivoSight SKINTELL Central wavelength 1305 nm 1300 nm 850 nm Shorter Lateral resolution 7,5 µm 3-4 µm 6.3 µm Intermediate Axial resolution 5-7 µm 3 µm 6.3 µm Intermediate Field of view 6 mm x 6 mm 1,8 mm x 1,5 mm 8 mm x 8 mm Bigger Depth of penetration 1-2 mm 0,5 mm 0,6 mm like Agfa Imaging speed 6 fps 30 s full acquisition B-scan in 3.6 s Advantage due to the // acquisition Polarisation sensitive No No Possible Polarisation sensitive Unit price 95 k 85 k - production will stop at the end of k expected Less expensive

14 Array-type MOEMS Mirau interferometer 3 microoptical wafers microlens doublet: 4x4 array of plano-convex microlenses 4x4 array of reference micro-mirrors planar beam splitter MEMS z-scanner wafer z-actuated platform carrying reference phase-shifted mirrors (vertical comb-drive) Vertical assembly by multi-wafer bonding including electrical interconnections

15 Doublet of 4x4 microlens matrices Thermal reflow of glass in Si cavity plano-convex lenses, spherical shape with NA=0.12 lens matrices with high fill-factor (pitch 2 mm) sag: 0.5 μm within a matrix surface roughness < λ/30 J Albero et al., Optics Letters 41 (1), 96-99, (2016).

16 Characterisation of Mirau lens Cross section of the lens Optimization of glass reflow into Si cavity About the thermal reflow in Si cavity shape and sag are depending from the reflow temperature tendency to be perfectly spherical at the center (<1 mm of diameter) and parabolic at the edge ZY slice ZX slice Focal depth ~ 250mm Transverse and longitudinal cross section of PSF J Albero et al. Optics express 23 (9), , (2015).

17 Transmission Beam splitter wafer Based on one upper substrate Silicon oxynitride SiO x N y mono- or multi-layers T/R 90/10 80/20 70/30 60/40 50/50 Layers number n h H (nm) n h H (nm) n h H (nm) n h H (nm) n h H (nm) Transmission vs λ Two technologies developed SiO x N y mono- or multi-layers TiO 2 mono-layer (high index) Our source Single layer wavelength (nm)

18 Z-scanner carrying reference mirrors Challenges Large platform (8x8mm 2 ): transmissive & reflective optical functions, strong actuation force Accuracy of out-of-plane displacement Mirror Released structure Glass membrane Actuator: electrostatic vertical comb-drive on SOI 16 ref. mirrors (400x400 μm 2 ), aperture of 1.8 mm Displacement sensors: capacitive detection Two strategies for mirror platform: glass membrane silicon springs Glass membrane: 25 μm thick, integration of glass structure on SOI wafer Easier solution: no impact of springs on the imaging quality J Lullin et al., Optics Letters 40 (10), , (2015).

19 Packaged Z-actuator: characterized version Mirrors Springs Actuators Sensors Wire bonding

20 Characterisation of Z-actuator MEMS Analyzer (Polytec) Dynamic measurements Dynamic and semi-static measurements Static measurements Resonant frequency: 460 Hz J. Lullin, et al., J. Micromech. Microeng. 26, (2015)

21 Assembly of Mirau stack by multi-wafer bonding front side Interface Bonding step A0, A, A1 lens+lens D W3+W4 back side C W2+ (W3/W4) B W1+(W2/W3/W4) All anodic bonding W2 W1 W3 W4 Developed N-bonding process is promising for the integration of a Mirau interferometer W3, W4 front side back side WS Wang, et al., Proc. SPIE 9375, SPIE Photonics West

22 OCT microsystem Mirau interferometer microlens side (FEMTO-ST) High resolution camera (CSEM) Mirau interferometer reference mirror side (FEMTO-ST) 22 Complete OCT microsystem (Statice)

23 Micro-OCT imaging A good OCT imager is capable of revealing the fine details of skin-tissue microstructure with a lateral resolution < 10 µm and an imaging depth < 1 mm. Such characteristics make OCT highly interesting to dermatologists. 4 mm 4 mm Whate is it desired by dermatologue : reconstruction of skin microstructure with lateral resolution < 10 µm and depth < 1 mm. OCT image of a paint sample with varnish layer Sensibilité ~ 85 db 3D image of oignon layers

24 Conclusion and perspectives MOEMS technology has great potential to build miniature, low cost optical instruments for 3D imaging of biological samples and particularly can be applied in dermatology. We demonstrated that the architecture of a vertically integrated multi-wafer type OCT MEMS microscope is suitable for batch fabrication and assembly by multi-wafer bonding. Before Feb the OCT microscope will be validated at the Hospital through a series of translational trials in screening of skin lesions. 24