Cell type classification and isolation according to imaging and spatial characteristics, beyond traditional fluorescently labeled biomarkers, enable the development of new biological insight and establishment of connections between phenotypical, morphological, and genomic cell information in normal and diseased states. Here we demonstrate a 2D image-guided cell sorter and a 3D imaging flow cytometer using fast scanning laser excitation sources. Both systems feature a cameraless design, which reconstructs cell images from the temporal readout of photomultiplier tubes.
KEYWORDS: Microfluidics, Blood, Lab on a chip, Scattering, Point-of-care devices, Kidney, Signal detection, Laser scattering, Silicon, Digital signal processing
A point-of-care and home-care lab-on-a-chip (LoC) system that integrates a microfluidic spiral device as a concentrator with an optical-coding device as a cell enumerator is demonstrated. The LoC system enumerates white blood cells from dialysis effluent of patients receiving peritoneal dialysis. The preliminary results show that the white blood cell counts from our system agree well with the results from commercial flow cytometers. The LoC system can potentially bring significant benefits to end stage renal disease (ESRD) patients that are on peritoneal dialysis (PD).
We report a portable, low-cost, and high-performance microfluidics based fluorescence-activated cell sorter
(microFACS) system to isolate E.coli. cells in combination with a modified specific fluorescence labeling method called
tyramide signal amplification-fluorescence in situ hybridization (TSA-FISH). One of the primary challenges in studying
bacterial communities that elude cell culturing is to isolate of low abundance bacteria cell from heterogeneous microbial
samples. The proposed TSA-FISH protocol is flow cytometry compatible and yields about 10-fold enhancement in
fluorescence labeling intensity over widely used standard FISH staining methods. Teflon AF coated optofluidic
waveguide and space-time coding with a matched filter algorithm enhance its detection sensitivity. The microFACS is
also able to enrich TSA-FISH labeled E.coli. cells by a factor of 223 with an integrated piezoelectric actuator and realtime
control electronics system. The microFACS in conjunction with the modified TSA-FISH technologies demonstrates a highly effective and low cost solution potentially for the genomic complexity of complex bacterial communities.
This work reports a miniaturized laparoscopic zoom camera that can significantly improve vision for minimally invasive surgery (MIS), also known as laparoscopic surgery. The laparoscopic zoom camera contains bioinspired fluidic lenses that can change curvature and focal length in a manner similar to the crystalline lenses in human eyes. The traditional laparoscope is long, rigid, and made of fixed glass lenses with a fixed field of view. The constricted vision of a laparoscope is often an inconvenience and plays a role in many surgical injuries. To further advance MIS technology, we developed a new type of laparoscopic camera that has a total length of less than 17 mm, greater than 4× optical zoom, and 100 times higher sensitivity than today's laparoscope allowing it to work under illumination as low as 300 lux. All these unique features are enabled by the technology of bioinspired fluidic lenses having a dynamic range over 100 diopters and being convertible between a convex and concave shape.
We developed a new type of optical lens device that can change its curvature like crystalline lens in human eye. The
curvature changing capability of the lens allows for a tremendous tuning range in its optical power and subsequently
enables miniaturized imaging systems that can perform autofocus, optical zoom, and other advanced functions. In this
paper, we study the physical properties of bio-inspired fluidic lenses and demonstrate the optical functionality through
miniaturized optical systems constructed with such lenses. We report an auto-focusing optical system that can turn from
a camera to a microscope, and demonstrate more than 4X optical zoom with a very short total track length. Finally, we
demonstrate the benefits of fluidic lens zoom camera through minimally invasive gallbladder removal surgery.
We report on the development of an inexpensive, portable lab-on-a-chip flow cytometer system in which microfluidics,
photonics, and acoustics are integrated together to work synergistically. The system relies on fluid-filled twodimensional
on-chip photonic components such as lenses, apertures, and slab waveguides to allow for illumination laser
beam shaping, light scattering and fluorescence signal detection. Both scattered and fluorescent lights are detected by
photodetectors after being collected and guided by the on-chip optics components (e.g. lenses and waveguides). The
detected light signal is imported and amplified in real time and triggers the piezoelectric actuator so that the targeted
samples are directed into desired reservoir for subsequent advanced analysis. The real-time, closed-loop control system
is developed with field-programmable-gate-array (FPGA) implementation. The system enables high-throughput (1-
10kHz operation), high reliability and low-powered (<1mW) fluorescence activated cell sorting (FACS) on a chip. The
microfabricated flow cytometer can potentially be used as a portable, inexpensive point-of-care device in resource poor
environments.
Miniaturized imaging systems have become ubiquitous as they are found in an ever-increasing number of devices, such
as cellular phones, personal digital assistants, and web cameras. Until now, the design and fabrication methodology of
such systems have not been significantly different from conventional cameras. The only established method to achieve
focusing is by varying the lens distance. On the other hand, the variable-shape crystalline lens found in animal eyes
offers inspiration for a more natural way of achieving an optical system with high functionality.
Learning from the working concepts of the optics in the animal kingdom, we developed bio-inspired fluidic lenses for a
miniature universal imager with auto-focusing, macro, and super-macro capabilities. Because of the enormous dynamic
range of fluidic lenses, the miniature camera can even function as a microscope. To compensate for the image quality
difference between the central vision and peripheral vision and the shape difference between a solid-state image sensor
and a curved retina, we adopted a hybrid design consisting of fluidic lenses for tunability and fixed lenses for aberration
and color dispersion correction. A design of the world's smallest surgical camera with 3X optical zoom capabilities is
also demonstrated using the approach of hybrid lenses.
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