Compact, cost-effective and field-portable microscope prototype based on MISHELF microscopy

We report on a reduced cost, portable and compact prototype design of lensless holographic microscope with an illumination/detection scheme based on wavelength multiplexing, working with single hologram acquisition and using a fast convergence algorithm for image processing. All together, MISHELF (initials coming from Multi-Illumination Single-Holographic-Exposure Lensless Fresnel) microscopy allows the recording of three Fresnel domain diffraction patterns in a single camera snap-shot incoming from illuminating the sample with three coherent lights at once. Previous implementations have proposed an illumination/detection procedure based on a tuned (illumination wavelengths centered at the maximum sensitivity of the camera detection channels) configuration but here we report on a detuned (non-centered ones) scheme resulting in prototype miniaturization and cost reduction. Thus, MISHELF microscopy in combination with a novel and fast iterative algorithm allows high-resolution (μm range) phase-retrieved (twin image elimination) quantitative phase imaging of dynamic events (video rate recording speed). The performance of this microscope prototype is validated through experiments using both amplitude (USAF resolution test) and complex (live swine sperm cells and flowing microbeads) samples. The proposed method becomes in an alternative instrument improving some capabilities of existing lensless microscopes.

[1]  Aydogan Ozcan,et al.  High-throughput lensfree 3D tracking of human sperms reveals rare statistics of helical trajectories , 2012, Proceedings of the National Academy of Sciences.

[2]  Vicente Micó,et al.  Common-path phase-shifting lensless holographic microscopy. , 2010, Optics letters.

[3]  V. Micó,et al.  Quantitative phase microscopy using defocusing by means of a spatial light modulator. , 2010, Optics express.

[4]  G. Pedrini,et al.  Lensless phase microscopy using phase retrieval with multiple illumination wavelengths. , 2012, Applied optics.

[5]  Aydogan Ozcan,et al.  Smart-phone based computational microscopy using multi-frame contact imaging on a fiber-optic array. , 2013, Lab on a chip.

[6]  Manfred H. Jericho,et al.  Submersible digital in-line holographic microscope , 2006 .

[7]  A. Ozcan,et al.  Maskless imaging of dense samples using pixel super-resolution based multi-height lensfree on-chip microscopy , 2012, Optics Express.

[8]  Vicente Micó,et al.  Lensless object scanning holography for two-dimensional mirror-like and diffuse reflective objects. , 2013, Applied optics.

[9]  Aydogan Ozcan,et al.  Sperm Trajectories Form Chiral Ribbons , 2013, Scientific Reports.

[10]  Bahram Javidi,et al.  Phase-shifting Gabor holography. , 2009, Optics letters.

[11]  Enrique Tajahuerce,et al.  Femtosecond digital lensless holographic microscopy to image biological samples. , 2013, Optics letters.

[12]  Vicente Micó,et al.  Wavefront holoscopy: application of digital in-line holography for the inspection of engraved marks in progressive addition lenses , 2014, Journal of biomedical optics.

[13]  I. Yamaguchi,et al.  Phase-shifting digital holography. , 1997, Optics letters.

[14]  James P Ryle,et al.  Lensless multispectral digital in-line holographic microscope. , 2011, Journal of biomedical optics.

[15]  M H Jericho,et al.  Comment on "Reconstruction algorithm for high-numerical-aperture holograms with diffraction-limited resolution". , 2006, Optics letters.

[16]  I. Yamaguchi,et al.  Three-dimensional microscopy with phase-shifting digital holography. , 1998, Optics letters.

[17]  Aydogan Ozcan,et al.  Field-Portable Pixel Super-Resolution Colour Microscope , 2013, PloS one.

[18]  Sai Siva Gorthi,et al.  A semi-automated, field-portable microscopy platform for clinical diagnostic applications , 2015 .

[19]  D. Gabor.  A New Microscopic Principle , 1948, Nature.

[20]  W Xu,et al.  Digital in-line holography for biological applications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Demetri Psaltis,et al.  Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging , 2008, Proceedings of the National Academy of Sciences.

[22]  Laura Waller,et al.  Phase from chromatic aberrations. , 2010, Optics express.

[23]  Laura Waller,et al.  Multi-Contrast Imaging and Digital Refocusing on a Mobile Microscope with a Domed LED Array , 2015, PloS one.

[24]  Derek K. Tseng,et al.  Detection of waterborne parasites using field-portable and cost-effective lensfree microscopy. , 2010, Lab on a chip.

[25]  Guoan Zheng,et al.  Imaging and Identification of Waterborne Parasites Using a Chip-Scale Microscope , 2014, PloS one.

[26]  Vicente Micó,et al.  Improved quantitative phase imaging in lensless microscopy by single-shot multi-wavelength illumination using a fast convergence algorithm. , 2015, Optics express.

[27]  Changhuei Yang,et al.  A smartphone-based chip-scale microscope using ambient illumination. , 2014, Lab on a chip.

[28]  Zeev Zalevsky,et al.  Superresolved digital in-line holographic microscopy for high-resolution lensless biological imaging. , 2010, Journal of biomedical optics.

[29]  Patrik Langehanenberg,et al.  Automated three-dimensional tracking of living cells by digital holographic microscopy. , 2009, Journal of biomedical optics.

[30]  Pietro Ferraro,et al.  4D tracking of clinical seminal samples for quantitative characterization of motility parameters. , 2014, Biomedical optics express.

[31]  Stefan Witte,et al.  High-speed multi-wavelength Fresnel diffraction imaging. , 2014, Optics express.

[32]  G. Pedrini,et al.  Whole optical wave field reconstruction from double or multi in-line holograms by phase retrieval algorithm. , 2003, Optics express.

[33]  Daniel A. Fletcher,et al.  Low-Cost Mobile Phone Microscopy with a Reversed Mobile Phone Camera Lens , 2014, PloS one.

[34]  Paul Petruck,et al.  High resolution (NA = 0.8) in lensless in-line holographic microscopy with glass sample carriers. , 2011, Optics letters.

[35]  Aydogan Ozcan,et al.  Imaging without lenses: achievements and remaining challenges of wide-field on-chip microscopy , 2012, Nature Methods.

[36]  Derek Tseng,et al.  Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications. , 2010, Lab on a chip.

[37]  Ke Xiao,et al.  Flow visualization and flow cytometry with holographic video microscopy , 2010, OPTO.

[38]  Amy L. Gryshuk,et al.  Cell-Phone-Based Platform for Biomedical Device Development and Education Applications , 2011, PloS one.

[39]  Jan F. Jikeli,et al.  Sperm navigation along helical paths in 3D chemoattractant landscapes , 2015, Nature Communications.

[40]  R Riesenberg,et al.  Reconstruction of high-resolution holographic microscopic images. , 2009, Optics letters.

[41]  N. Streibl.  Phase imaging by the transport equation of intensity , 1984 .

[42]  Derek Tseng,et al.  Lensfree microscopy on a cellphone. , 2010, Lab on a chip.

[43]  Hongying Zhu,et al.  Optical imaging techniques for point-of-care diagnostics. , 2013, Lab on a chip.

[44]  M. Teague.  Deterministic phase retrieval: a Green’s function solution , 1983 .

[45]  Stanislas Leibler,et al.  Microbial population dynamics by digital in-line holographic microscopy. , 2010, The Review of scientific instruments.

[46]  L. Repetto,et al.  Lensless digital holographic microscope with light-emitting diode illumination. , 2004, Optics letters.

[47]  Kaikai Guo,et al.  FPscope: a field-portable high-resolution microscope using a cellphone lens. , 2014, Biomedical optics express.

[48]  Daniel A. Fletcher,et al.  Quantitative Imaging with a Mobile Phone Microscope , 2014, PloS one.

[49]  Mark C. Pierce,et al.  Portable, Battery-Operated, Low-Cost, Bright Field and Fluorescence Microscope , 2010, PloS one.

[50]  Daniel Filippini,et al.  Biosensing with cell phones. , 2014, Trends in biotechnology.

[51]  Pasquale Memmolo,et al.  Recent advances in holographic 3D particle tracking , 2015 .

[52]  Vicente Micó,et al.  Surpassing digital holography limits by lensless object scanning holography. , 2012, Optics express.

[53]  Demetri Psaltis,et al.  Optofluidic microscopy--a method for implementing a high resolution optical microscope on a chip. , 2006, Lab on a chip.

[54]  Tomasz S. Tkaczyk,et al.  All-plastic miniature fluorescence microscope for point-of-care readout of bead-based bioassays , 2015, Journal of biomedical optics.

[55]  Aydogan Ozcan,et al.  Field-portable lensfree tomographic microscope. , 2011, Lab on a Chip.

[56]  G. L. Rogers.  XIV.—Experiments in Diffraction Microscopy , 1952, Proceedings of the Royal Society of Edinburgh. Section A. Mathematical and Physical Sciences.

[57]  Aydogan Ozcan,et al.  Field-portable reflection and transmission microscopy based on lensless holography , 2011, Biomedical optics express.

[58]  A. Ozcan,et al.  Lensfree on-chip microscopy over a wide field-of-view using pixel super-resolution , 2010, Optics express.

[59]  David N Breslauer,et al.  Mobile Phone Based Clinical Microscopy for Global Health Applications , 2009, PloS one.