Changhuei Yang

Sensitivity advantage of swept source and Fourier domain optical coherence tomography

We present theoretical and experimental results which demonstrate the superior sensitivity of swept source (SS) and Fourier domain (FD) optical coherence tomography (OCT) techniques over the conventional time domain (TD) approach. We show that SS- and FD-OCT have equivalent expressions for system signal-to-noise ratio which result in a typical sensitivity advantage of 20-30dB over TD-OCT. Experimental verification is provided using two novel spectral discrimination (SD) OCT systems: a differential fiber-based 800nm FD-OCT system which employs deep-well photodiode arrays, and a differential 1300nm SS-OCT system based on a swept laser with an 87nm tuning range.

Developing optofluidic technology through the fusion of microfluidics and optics

We describe devices in which optics and fluidics are used synergistically to synthesize novel functionalities. Fluidic replacement or modification leads to reconfigurable optical systems, whereas the implementation of optics through the microfluidic toolkit gives highly compact and integrated devices. We categorize optofluidics according to three broad categories of interactions: fluid–solid interfaces, purely fluidic interfaces and colloidal suspensions. We describe examples of optofluidic devices in each category.

Wide-field, high-resolution Fourier ptychographic microscopy

In this article, we report an imaging method, termed Fourier ptychographic microscopy (FPM), which iteratively stitches together a number of variably illuminated, low-resolution intensity images in Fourier space to produce a wide-field, high-resolution complex sample image. By adopting a wavefront correction strategy, the FPM method can also correct for aberrations and digitally extend a microscope’s depth-of-focus beyond the physical limitations of its optics. As a demonstration, we built a microscope prototype with a resolution of 0.78 μm, a field-of-view of ~120 mm2, and a resolution-invariant depth-of-focus of 0.3 mm (characterized at 632 nm). Gigapixel colour images of histology slides verify FPM’s successful operation. The reported imaging procedure transforms the general challenge of high-throughput, high-resolution microscopy from one that is coupled to the physical limitations of the system’s optics to one that is solvable through computation.

Spectral-domain phase microscopy.

Broadband interferometry is an attractive technique for the detection of cellular motions because it provides depth-resolved phase information via coherence gating. We present a phase-sensitive technique called spectral-domain phase microscopy (SDPM). SDPM is a functional extension of spectral-domain optical coherence tomography that allows for the detection of nanometer-scale motions in living cells. The sensitivity of the technique is demonstrated, and its calibration is verified. A shot-noise limit to the displacement sensitivity of this technique is derived. Measurement of cellular dynamics was performed on spontaneously beating cardiomyocytes isolated from chick embryos.

Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging

Low-cost and high-resolution on-chip microscopes are vital for reducing cost and improving efficiency for modern biomedicine and bioscience. Despite the needs, the conventional microscope design has proven difficult to miniaturize. Here, we report the implementation and application of two high-resolution (≈0.9 μm for the first and ≈0.8 μm for the second), lensless, and fully on-chip microscopes based on the optofluidic microscopy (OFM) method. These systems abandon the conventional microscope design, which requires expensive lenses and large space to magnify images, and instead utilizes microfluidic flow to deliver specimens across array(s) of micrometer-size apertures defined on a metal-coated CMOS sensor to generate direct projection images. The first system utilizes a gravity-driven microfluidic flow for sample scanning and is suited for imaging elongate objects, such as Caenorhabditis elegans; and the second system employs an electrokinetic drive for flow control and is suited for imaging cells and other spherical/ellipsoidal objects. As a demonstration of the OFM for bioscience research, we show that the prototypes can be used to perform automated phenotype characterization of different Caenorhabditis elegans mutant strains, and to image spores and single cellular entities. The optofluidic microscope design, readily fabricable with existing semiconductor and microfluidic technologies, offers low-cost and highly compact imaging solutions. More functionalities, such as on-chip phase and fluorescence imaging, can also be readily adapted into OFM systems. We anticipate that the OFM can significantly address a range of biomedical and bioscience needs, and engender new microscope applications.

Instantaneous complex conjugate resolved spectral domain and swept-source OCT using 3x3 fiber couplers

We report that the complex conjugate artifact in Fourier domain optical coherence tomography approaches (including spectral domain and swept source OCT) may be resolved by the use of novel interferometer designs based on 3x3 and higher order fiber couplers. Interferometers built from NxN (N>2) truly fused fiber couplers provide simultaneous access to non-complementary phase components of the complex interferometric signal. These phase components may be converted to quadrature components by trigonometric manipulation, then inverse Fourier transformed to obtain A-scans and images with resolved complex conjugate artifact. We demonstrate instantaneous complex conjugate resolved Fourier domain OCT using 3x3 couplers in both spectral domain and swept source implementations. Complex conjugate artifact suppression by factors of ~20dB and ~25dB are demonstrated for spectral domain and swept source implementations, respectively.

Deep-tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light

Fluorescence imaging is one of the most important research tools in biomedical sciences. However, scattering of light severely impedes imaging of thick biological samples beyond the ballistic regime. Here we directly show focusing and high-resolution fluorescence imaging deep inside biological tissues by digitally time-reversing ultrasound-tagged light with high optical gain (~5×105). We confirm the presence of a time-reversed optical focus along with a diffuse background—a corollary of partial phase conjugation—and develop an approach for dynamic background cancellation. To illustrate the potential of our method, we image complex fluorescent objects and tumour microtissues at an unprecedented depth of 2.5 mm in biological tissues at a lateral resolution of 36 μm×52 μm and an axial resolution of 657 μm. Our results set the stage for a range of deep-tissue imaging applications in biomedical research and medical diagnostics.

Instantaneous quadrature low coherence interferometry with 3 x 3 fiber optic couplers

We present an interferometer topology based on 3 x 3 fiber couplers that gives instantaneous access to the magnitude and phase of die interferometric signal. We demonstrate its performance in heterodyne and homodyne detection with a broadband light source.

Cellular organization and substructure measured using angle-resolved low-coherence interferometry.

We measure the organization and substructure of HT29 epithelial cells in a monolayer using angle-resolved low-coherence interferometry. This new technique probes cellular structure by measuring scattered light, as in flow cytometry, but offers an advantage in that the structure can be examined in situ, avoiding the need to disrupt the cell monolayer. We determine the size distribution of the cell nuclei by fitting measured light-scattering spectra to the predictions of Mie theory. In addition, we obtain information about the cellular organization and substructure by examining the spatial correlations within the monolayer. A remarkable finding is that the spatial correlations over small length scales take the form of an inverse power law, indicating the fractal nature of the packing of the subcellular structures. We also identify spatial correlations on a scale large compared with the size of a cell, indicating an overlying order within the monolayer.

Implementation of a digital optical phase conjugation system and its application to study the robustness of turbidity suppression by phase conjugation

In this work, we report a novel high capacity (number of degrees of freedom) open loop adaptive optics method, termed digital optical phase conjugation (DOPC), which provides a robust optoelectronic optical phase conjugation (OPC) solution. We showed that our prototype can phase conjugate light fields with approximately 3.9 x 10(-3) degree accuracy over a range of approximately 3 degrees and can phase conjugate an input field through a relatively thick turbid medium (micro(s)l approximately 13). Furthermore, we employed this system to show that the reversing of random scattering in turbid media by phase conjugation is surprisingly robust and accommodating of phase errors. An OPC wavefront with significant spatial phase errors (error uniformly distributed from - pi/2 to pi/2) can nevertheless allow OPC reconstruction through a scattering medium with approximately 40% of the efficiency achieved with phase error free OPC.