Yu g Chen

Lasing in blood

Indocyanine green (ICG) is the only near-infrared dye approved by the U.S. Food and Drug Administration for clinical use. When injected in blood, ICG binds primarily to plasma proteins and lipoproteins, resulting in enhanced fluorescence. Recently, the optofluidic laser has emerged as a novel tool in bio-analysis. Laser emission has advantages over fluorescence in signal amplification, narrow linewidth, and strong intensity, leading to orders of magnitude increase in detection sensitivity and imaging contrast. Here we successfully demonstrate, to the best of our knowledge, the first ICG lasing in human serum and whole blood with the clinical ICG concentrations and the pump intensity far below the clinically permissible level. Furthermore, we systematically study ICG laser emission within each major serological component (albumins, globulins, and lipoproteins) and reveal the critical elements and conditions responsible for lasing. Our work marks a critical step toward eventual clinical and biomedical applications of optofluidic lasers using FDA approved fluorophores, which may complement or even supersede conventional fluorescence-based sensing and imaging.

Evaluation of holographic methods for imaging through biological tissue

Different holographic methods for imaging through biological tissue are evaluated and compared. The role of the source autocorrelation function is analyzed. A graphical plot for performance evaluation is introduced. Experimental results for the various methods are given, and possibilities for further development are indicated.

Comparison of various holographic techniques for imaging through biological tissue

Five different holographic methods for imaging through biological tissue, as well as other highly scattering media, are described.

A robust tissue laser platform for analysis of formalin-fixed paraffin-embedded biopsies

Laser emission-based detection and imaging technology has attracted significant interest in biomedical research due to its high sensitivity, narrow linewidth, and superior spectral and spatial resolution. Recent advances have further revealed the potential to use laser emission to investigate chromatin dynamics, as well as to diagnose cancer tissues based on nuclear biomarkers. To move the laser emission based detection technology a step further towards practical use, in this work, we developed a highly robust tissue laser platform by microfabricating an SU8 spacer with a fixed height on the top mirror of the Fabry-Pérot (FP) cavity, which allows generation of reproducible and stable lasing results regardless of tissue thickness. Then we applied this platform to achieve lasing emission from formalin-fixed, paraffin-embedded (FFPE) lung tissues, which account for an overwhelming fraction of tissues collected for research and clinical use worldwide. We further showed that the cancer and normal FFPE lung tissues can be distinguished by their respective lasing thresholds. Two different tissue thicknesses (10 μm and 5 μm) commonly used in pathological labs were explored. Finally, we tested three additional types of tissues (colon, stomach, and breast) that were prepared independently by lab technicians in a pathology lab in China and shipped to the US in order to validate the general applicability and practicality of the laser emission-based technology as well as the corresponding sample preparation protocol and the tissue laser platform. Our work will not only vastly broaden the applications of laser emission-based detection/imaging technology but also help translate it from the laboratory to an automated system for clinical practice that may eventually benefit biomedicine and biological research.

Multiplexed lasing in tissues

Biolasers are an emerging technology for next generation biochemical detection and clinical applications. Progress has recently been made to achieve lasing from biomolecules and single living cells. Tissues, which consist of cells embedded in extracellular matrix, mimic more closely the actual complex biological environment in a living body and therefore are of more practical significance. Here, we developed a highly versatile tissue laser platform, in which tissues stained with fluorophores are sandwiched in a high-Q Fabry-Pérot microcavity. Distinct lasing emissions from muscle and adipose tissues stained respectively with fluorescein isothiocyanate (FITC) and boron-dipyrromethene (BODIPY), and hybrid muscle/adipose tissue with dual-staining were achieved with a threshold of only ~10 μJ/mm2. Additionally, we investigated how tissue structure/geometry, tissue thickness, and staining dye concentration affect the tissue laser. It is further found that, despite large fluorescence spectral overlap between FITC and BODIPY in tissues, their lasing emissions could be clearly distinguished and controlled due to their narrow lasing bands and different lasing thresholds, thus enabling highly multiplexed detection. Our tissue laser platform can be broadly applicable to various types of tissues/diseases. It provides a new tool for a wide range of biological and biomedical applications, such as diagnostics/screening of tissues and identification/monitoring of biological transformations in tissue engineering.

Phase conjugation, holography, and imaging through inhomogeneous media

Holography may be carried out in a wide a variety of materials and devices, such as photographic film, photopolymers, CCD cameras and nonlinear crystals. The commonality of these is the nonlinear characteristic that results in the mixing of two light beams to produce a difference term. The bases for the holographic methods to image through inhomogeneities are varied. The basis may be the generation of a conjugate field, as in holographic phase conjugation. It may be the time averaging effect of the holographic process. It may be the gating effect of short pulse light, or equivalently, the temporal coherence function. Or, it may be the light source spatial coherence function. We offer examples for each category.<<ETX>>

Use of holography for imaging through inhomogeneous media

Electronic holography for imaging through biological tissue is described. A number of processes are given, including the holographic implementation of the first arriving light method, the broad source method, as well as variations on these methods. The equipment is discussed in some detail, including the camera-computer interactions.

Imaging through biological tissue with holography

Various holographic methods of imaging through highly scattering media such as biological tissue are described. Experimental results are given.