Recent advances in deep submicron CMOS technologies and improved pixel designs have enabled CMOS-based imagers to surpass charge-coupled devices (CCD) imaging technology for mainstream applications. The parallel outputs that CMOS imagers can offer, in addition to complete camera-on-a-chip solutions due to being fabricated in standard CMOS technologies, result in compelling advantages in speed and system throughput. Since there is a practical limit on the minimum pixel size (4~5 μm) due to limitations in the optics, CMOS technology scaling can allow for an increased number of transistors to be integrated into the pixel to improve both detection and signal processing. Such smart pixels truly show the potential of CMOS technology for imaging applications allowing CMOS imagers to achieve the image quality and global shuttering performance necessary to meet the demands of ultrahigh-speed applications. In this paper, a review of CMOS-based high-speed imager design is presented and the various implementations that target ultrahigh-speed imaging are described. This work also discusses the design, layout and simulation results of an ultrahigh acquisition rate CMOS active-pixel sensor imager that can take 8 frames at a rate of more than a billion frames per second (fps).

We report the design and development of a compact optical fiber-based apparatus for in situ time-resolved laser-induced fluorescence spectroscopy (tr-LIFS) of biological systems. The apparatus is modular, optically robust, and compatible with the clinical environment. It incorporates a dual output imaging spectrograph, a gated multichannel plate photomultiplier (MCP-PMT), an intensified charge-coupled-device (ICCD) camera, and a fast digitizer. It can accommodate various types of light sources and optical fiber probes for selective excitation and remote light delivery/collection as required by different applications. The apparatus allows direct recording of the entire fluorescence decay with high sensitivity (nM range fluorescein dye concentration with signal-to-noise ratio of 46) and with four decades dynamic range. It is capable of resolving a broad range of fluorescence lifetimes from hundreds of picoseconds (as low as 300 ps) using the MCP-PMT coupled to the digitizer to milliseconds using the ICCD. The data acquisition and analysis process is fully automated, enabling fast recording of fluorescence intensity decay across the entire emission spectrum (0.8 s per wavelength or ∼40 s for a 200 nm wavelength range at 5 nm increments). The spectral and temporal responses of the apparatus were calibrated and its performance was validated using fluorescence lifetime standard dyes (Rhodamin B, 9-cyanoanthracene, and rose Bengal) and tissue endogenous fluorophores (elastin, collagen, nicotinamide adenine dinucleotide, and flavin adenine dinucleotide). Fluorescence decay lifetimes and emission spectra of all tested compounds measured with the current tr-LIFS apparatus were found in good agreement with the values reported in the literature. The design and performance of tr-LIFS apparatus have enabled in vivo studies of atherosclerotic plaques and brain tumors.

Fluorescence spectroscopy is a nondestructive optical method extensively used to probe complex biological systems, including cells and tissues for biochemical, functional, and morphological changes associated with pathological conditions. Such an approach has potential for noninvasive diagnosis in vivo.^{1 2 3} Fluorescence measurements can be categorized as either static (steady state or time integrated) or dynamic (time- resolved). While steady state techniques provide an integrate spectrum over time that gives information about fluorescence emission intensity and spectral distribution, time-resolved techniques measure the dynamically evolving fluorescence emission, providing additional insight into the molecular species of the sample (e.g., the number of fluorescence species and their contribution to the overall emission) and/or changes in the local environment.^{2 3}

The goal of this study is to determine the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for delineation of brain tumor from surrounding normal tissue in order to assist the neurosurgeon in near-complete tumor excision. A time-domain TR-LIFS prototype apparatus (gated photomultiplier detection, fast digitizer) was used for recording tissue autofluorescence in normal cortex (NC), normal white matter (NWM), and various grades of gliomas intraoperatively. Tissue fluorescence was induced with a pulsed nitrogen laser (337 nm, 700 ps), and the intensity decay profiles were recorded in the 360- to 550-nm spectral range (10-nm interval). Histopathological analysis (hematoxylin & eosin) of the biopsy samples taken from the site of TR-LIFS measurements was used for validation of spectroscopic results. Preliminary results on 17 patients demonstrate that normal cortex (N=16) and normal white matter (N=3) show two peaks of fluorescence emission at 390 nm (lifetime=1.8±0.3 ns) and 460 nm (lifetime=0.8±0.1 ns). The 390-nm emission peak is absent in low-grade glioma (N=5; lifetime=1.1 ns) and reduced in high-grade glioma (N=9; lifetime=1.7±0.4 ns). The emission characteristics at 460 nm in all tissues correlated with the nicotinamide adenine dinucleotide fluorescence (peak: 440 to 460 nm; lifetime: 0.8 to 1.0 ns). These findings demonstrate the potential of using TR-LIFS as a tool for enhanced delineation of brain tumors during surgery. In addition, this study evaluates similarities and differences between TR-LIFS signatures of brain tumors obtained in vivo and those previously reported in ex vivo brain tumor specimens.

Aqueous-based coatings using combinations of polydopamine (PDA) (as bioadhesive) and grafted polyethylene glycol (PEG) (as antifouling agent) have been reported to reduce biofouling on multiple material surfaces. However, the achievable PEG grafting density and antifouling performance are limited, leaving exposed PDA to provide sites for attachment of proteins and cells. In the present work, we investigate the polymerization of dopamine on three substrate materials, polycarbonate membrane (PC), polydimethyl siloxane (PDMS), and soda lime glass, to evaluate the utility of the PDA coatings for application to multiple materials. Additionally, we propose that the PDA–PEG method may be improved by “backfilling” with bovine serum albumin (BSA) as a blocker covering exposed PDA. AFM and ellipsometry studies revealed substantial differences in PDA thickness and roughness on each material despite their being modified under the same conditions. X-ray photoelectron spectroscopy (XPS) and water contact angle data revealed differences in PEG grafting on these materials as a consequence of varying PDA surface roughness, with the highest PEG coverage achieved on PC–PDA surfaces of intermediate roughness and lower PEG attachment on smoother PDMS–PDA surfaces. Fibrinogen adsorption experiments showed significantly less fouling on PDA–BSA surfaces compared to PDA–PEG for all three substrates, the larger BSA molecules presumably providing greater coverage of the PDA. On the PC and PDMS substrates, backfilling the PDA–PEG surfaces with BSA gave significant reductions in fibrinogen adsorption, with the lowest adsorption of 75 ng cm⁻² achieved on PC–PDA–PEG/BSA.