MEMS-in-the-lens architecture for a miniature high-NA laser scanning microscope

Tianbo Liu; Milind Rajadhyaksha; David L. Dickensheets

doi:10.1038/s41377-019-0167-5

Go to Nature Website

Your Location：

Home >

Browse articles >

MEMS-in-the-lens architecture for a miniature high-NA laser scanning microscope

Article

- MEMS-in-the-lens architecture for a miniature high-NA laser scanning microscope
- Light: Science & Applications Vol. 8, Issue 4, Pages: 527-537(2019)
- Affiliations：
  
  1.Electrical and Computer Engineering Department, Montana State University, Bozeman, MT 59715, USA
  2.Dermatology Department, Memorial Sloan Kettering Cancer Center, New York, NY 10022, USA
- Author bio：
  
  David L. Dickensheets (davidd@montana.edu)
- Funds：
- DOI：10.1038/s41377-019-0167-5
  CLC：
- Published：2019，
  
  Published Online：26 June 2019，
  
  Received：05 December 2018，
  
  Revised：24 May 2019，
  
  Accepted：30 May 2019
- Accepted：
Scan QR Code
Liu, T. B., Rajadhyaksha, M. & Dickensheets, D. L. MEMS-in-the-lens architecture for a miniature high-NA laser scanning microscope. Light: Science & Applications, 8, 527-537 (2019).
DOI：

Liu, T. B., Rajadhyaksha, M. & Dickensheets, D. L. MEMS-in-the-lens architecture for a miniature high-NA laser scanning microscope. Light: Science & Applications, 8, 527-537 (2019). DOI： 10.1038/s41377-019-0167-5.

摘要

Abstract

Laser scanning microscopes can be miniaturized for in vivo imaging by substituting optical microelectromechanical system (MEMS) devices in place of larger components. The emergence of multifunctional active optical devices can support further miniaturization beyond direct component replacement because those active devices enable diffraction-limited performance using simpler optical system designs. In this paper

we propose a catadioptric microscope objective lens that features an integrated MEMS device for performing biaxial scanning

axial focus adjustment

and control of spherical aberration. The MEMS-in-the-lens architecture incorporates a reflective MEMS scanner between a low-numerical-aperture back lens group and an aplanatic hyperhemisphere front refractive element to support high-numerical-aperture imaging. We implemented this new optical system using a recently developed hybrid polymer/silicon MEMS three-dimensional scan mirror that features an annular aperture that allows it to be coaxially aligned within the objective lens without the need for a beam splitter. The optical performance of the active catadioptric system is simulated and imaging of hard targets and human cheek cells is demonstrated with a confocal microscope that is based on the new objective lens design.

关键词

Keywords

references

Tomita, Y. et al. Long-term in vivo investigation of mouse cerebral microcirculation by fluorescence confocal microscopy in the area of focal ischemia.J. Cereb. Blood Flow. Metab.25, 858-867 (2005)..

Kerr, J. N.&Denk, W. Imaging in vivo: watching the brain in action.Nat. Rev. Neurosci.9, 195-205 (2008)..

Horton, N. G. et al. In vivo three-photon microscopy of subcortical structures within an intact mouse brain.Nat. Photonics7, 205-209 (2013)..

Dombeck, D. A. et al. Imaging large-scale neural activity with cellular resolution in awake, mobile mice.Neuron56, 43-57 (2007)..

Kobat, D., Horton, N. G.&Xu, C. In vivo two-photon microscopy to 1.6-mm depth in mouse cortex.J. Biomed. Opt.16, 106014 (2011)..

Davalos, D. et al. Stable in vivo imaging of densely populated glia, axons and blood vessels in the mouse spinal cord using two-photon microscopy.J. Neurosci. Methods169, 1-7 (2008)..

König, K. et al. Optical skin biopsies by clinical CARS and multiphoton fluorescence/SHG tomography.Laser Phys. Lett.8, 465-468 (2011)..

Ulrich, M.&Lange-Asschenfeldt, S. In vivo confocal microscopy in dermatology: from research to clinical application.J. Biomed. Opt.18, 061212 (2013)..

Guitera, P. et al. In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions.J. Invest. Dermatol.129, 131-138 (2009)..

Guitera, P. et al. In vivo confocal microscopy for diagnosis of melanoma and basal cell carcinoma using a two-step method: analysis of 710 consecutive clinically equivocal cases.J. Invest. Dermatol.132, 2386-2394 (2012)..

Nori, S. et al. Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study.J. Am. Acad. Dermatol.51, 923-930 (2004)..

Rajadhyaksha, M. et al. In vivo confocal scanning laser microscopy of human skin Ⅱ: advances in instrumentation and comparison with histology.J. Invest. Dermatol.113, 293-303 (1999)..

Zong, W. et al. Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice.Nat. Methods14, 713-719 (2017)..

Piyawattanametha, W. et al. In vivo brain imaging using a portable 2.9 g two-photon microscope based on a microelectromechanical systems scanning mirror.Opt. Lett.34, 2309-2311 (2009)..

Liu, L. et al. MEMS-based 3D confocal scanning microendoscope using MEMS scanners for both lateral and axial scan.Sens. Actuators A Phys.215, 89-95 (2014)..

Fu, L. et al. Nonlinear optical endoscopy based on a double-clad photonic crystal fiber and a MEMS mirror.Opt. Express14, 1027-1032 (2006)..

Gilchrist, K. H. et al. Piezoelectric scanning mirrors for endoscopic optical coherence tomography.J. Micromech. Microeng.19, 095012 (2009)..

Piyawattanametha, W.&Wang, T. D. MEMS-based dual-axes confocal microendoscopy.IEEE J. Sel. Top. Quantum Electron.16, 804-814 (2010)..

Wang, Y. et al. Portable oral cancer detection using a miniature confocal imaging probe with a large field of view.J. Micromech. Microeng.22, 065001 (2012)..

Liu, J. T. et al. Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional microelectromechanical systems scanner.Opt. Lett.32, 256-258 (2007)..

Li, H. et al. Integrated monolithic 3D MEMS scanner for switchable real time vertical/horizontal cross-sectional imaging.Opt. Express24, 2145-2155 (2016)..

Duan, X. et al. Three-dimensional side-view endomicroscope for tracking individual cells in vivo.Biomed. Opt. Express8, 5533-5545 (2017)..

Jia, K., Samuelson, S. R.&Xie, H. K. High-fill-factor micromirror array with hidden bimorph actuators and tip-tilt-piston capability.J. Microelectromech. Syst.20, 573-582 (2011)..

Liao, W. et al. A tip-tilt-piston micromirror with symmetrical lateral-shift-free piezoelectric actuators.IEEE Sens. J.13, 2873-2881 (2013)..

Shao, Y., Dickensheets, D. L.&Himmer, P. 3-D MOEMS mirror for laser beam pointing and focus control.IEEE J. Sel. Top. Quantum Electron.10, 528-535 (2004)..

Strathman, M. et al. Dynamic focus-tracking MEMS scanning micromirror with low actuation voltages for endoscopic imaging.Opt. Express21, 23934-23941 (2013)..

Liu, T. et al. MEMS 3-D scan mirror with SU-8 membrane and flexures for high NA microscopy.J. Microelectromech. Syst.27, 719-729 (2018)..

Morrison, J. et al. Electrothermally actuated tip-tilt-piston micromirror with integrated varifocal capability.Opt. Express23, 9555-9566 (2015)..

Shin, H. J. et al. Fiber-optic confocal microscope using a MEMS scanner and miniature objective lens.Opt. Express15, 9113-9122 (2007)..

Maitland, K. C. et al. Single fiber confocal microscope with a two-axis gimbaled MEMS scanner for cellular imaging.Opt. Express14, 8604-8612 (2006)..

Arrasmith, C. L., Dickensheets, D. L.&Mahadevan-Jansen, A. MEMS-based handheld confocal microscope for in-vivo skin imaging.Opt. Express18, 3805-3819 (2010)..

Kumar, K., Hoshino, K.&Zhang, X. Handheld subcellular-resolution single-fiber confocal microscope using high-reflectivity two-axis vertical combdrive silicon microscanner.Biomed. Microdevices10, 653-660 (2008)..

Murakami, K. A miniature confocal optical scanning microscope for endoscopes. Proceedings of SPIE 5721, MOEMS Display and Imaging Systems Ⅲ. San Jose, California, United States: SPIE, 2005.

Bechtel, C. et al. Large field of view MEMS-based confocal laser scanning microscope for fluorescence imaging.Optik125, 876-882 (2014)..

Chen, S. L. et al. A fiber-optic system for dual-modality photoacoustic microscopy and confocal fluorescence microscopy using miniature components.Photoacoustics1, 30-35 (2013)..

Lu, C. D. etal. Handheld ultrahigh speed swept source optical coherence tomography instrument using a MEMS scanning mirror.Biomed. Opt. Express5, 293-311 (2014)..

Duan, X. et al. MEMS-based multiphoton endomicroscope for repetitive imaging of mouse colon.Biomed. Opt. Express6, 3074-3083 (2015)..

Rouse, A. R. et al. Design and demonstration of a miniature catheter for a confocal microendoscope.Appl. Opt.43, 5763-5771 (2004)..

Liang, C. et al. Design of a high-numerical-aperture miniature microscope objective for an endoscopic fiber confocal reflectance microscope.Appl. Opt.41, 4603-4610 (2002)..

Kester, R. T. et al. High numerical aperture microendoscope objective for a fiber confocal reflectance microscope.Opt. Express15, 2409-2420 (2007)..

Sun, J. et al. 3D in vivo optical coherence tomography based on a low-voltage, large-scan-range 2D MEMS mirror.Opt. Express18, 12065-12075 (2010)..

Jung, W. et al. Three-dimensional endoscopic optical coherence tomography by use of a two-axis microelectromechanical scanning mirror.Appl. Phys. Lett.88, 163901 (2006)..

Aguirre, A. D. et al. Two-axis MEMS scanning catheter for ultrahigh resolution three-dimensional andEn faceimaging.Opt. Express15, 2445-2453 (2007)..

Mu, X. et al. MEMS micromirror integrated endoscopic probe for optical coherence tomography bioimaging.Sens. Actuators A Phys168, 202-212 (2011)..

Wang, T. D. et al. Dual-axes confocal microscopy with post-objective scanning and low-coherence heterodyne detection.Opt. Lett.28, 1915-1917 (2003)..

Wang, T. D. et al. Dual-axis confocal microscope for high-resolution in vivo imaging.Opt. Lett.28, 414-416 (2003)..

Rajadhyaksha, M., Anderson, R. R.&Webb, R. H. Video-rate confocal scanning laser microscope for imaging human tissues in vivo.Appl. Opt.38, 2105-2115 (1999)..

Ra, H. et al. Three-dimensional in vivo imaging by a handheld dual-axes confocal microscope.Opt. Express16, 7224-7232 (2008)..

Qiu, Z. et al. Targeted vertical cross-sectional imaging with handheld near-infrared dual axes confocal fluorescence endomicroscope.Biomed. Opt. Express4, 322-330 (2013)..

Born, M.&Wolf, E. Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light. 6th edn. (Amsterdam: Elsevier, 2013).

Knüttel, A.&Boehlau-Godau, M. Spatially confined and temporally resolved refractive index and scattering evaluation in human skin performed with optical coherence tomography.J. Biomed. Opt.5, 83-92 (2000)..

Bashkatov, A. N., Genina, E. A.&Tuchin, V. V. Optical properties of skin, subcutaneous, and muscle tissues: a review.J. Innov. Opt. Health Sci.4, 9-38 (2011)..

Urey, H. Torsional MEMS scanner design for high-resolution scanning display systems.Opt. Scanning4773, 27-38 (2002)..

Lukes, S. J.&Dickensheets, D. L. SU-8 2002 surface micromachined deformable membrane mirrors.J. Microelectromech. Syst.22, 94-106 (2013)..

Sung, K. et al. Near real time in vivo fibre optic confocal microscopy: sub-cellular structure resolved.J. Microsc.207, 137-145 (2002). MathSciNet.

Drezek, R. A. et al. Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid.Am. J. Obstet. Gynecol.182, 1135-1139 (2000)..

Liu, T.&Dickensheets, D. L. 3-Dimensional beam scanner for a handheld confocal dermoscope. 2016 International Conference on Optical MEMS and Nanophotonics. Singapore, (IEEE).

Lukes, S. J. et al. Four-zone varifocus mirrors with adaptive control of primary and higher-order spherical aberration.Appl. Opt.55, 5208-5218 (2016)..

Wilson, T.&Carlini, A. R. Size of the detector in confocal imaging systems.Opt. Lett.12, 227-229 (1987)..

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

⁰