We describe the design, fabrication, and performance of a class of simple handheld fluorometers. The devices consist of a sensor along with an integrated optical filter packaged in a handheld format. The sensor is a differential active pixel sensor with in-pixel correlated double sampling fabricated in a 0.5-mu m 2-poly 3-metal complementary metal-oxide semiconductor process and has a readout noise of 175.3 muV, reset noise of 360 muV, dynamic range of 59 dB, and conversion gain of 530 nV/e(-) . The filter is a high rejection chromophore embedded in a polymer film which is cast onto the chip. We show the results of bioassays utilizing two different single color fluorometers constructed by using the chromophores 2-(2'-hydroxy 5'-methylphenyl) benzotriazole and Sudan II with long-pass wavelengths of 400 nm and 540 nm, respectively. The bioassays measures metabolic activity and viability of biological cells, which are useful for cytotoxicity and pathogen detection applications.

We describe a bioMEMS system for confining and electrically interfacing to single cells for long-term studies. The system comprises microvials that can be covered and uncovered by lids actuated by polypyrrole/gold hinges. Within each vial are integrated bio-amplifiers and/or other sensing circuits to form a biolab-on-a-chip. We have developed a process sequence for fabricating lidded microvials with actuated lids on CMOS die. Initial testing of these "cell clinics" with bovine aortic smooth muscle cells yields successful sensing of the extracellular action potentials from bovine aortic smooth muscle cells using a custom VLSI bioamplifier.

We report on several techniques that have been pursued in our laboratories for packaging complementary metaloxide semiconductor (CMOS) sensors for use in biological environments, such as cell medium. These techniques are suited for single CMOS die ranging from 1.5 x 1.5 mm 2 to 3 x 3 mm 2 in area. The first method consisted of creating high aspect ratio structures from negative-tone photocurable resins to simultaneously encapsulate wirebonds from the chip to a ceramic package and create a cell culture well. The second technique used a photolithographically defined barrier on the die to allow the use of non-photocurable resins as encapsulants. The third method consisted of re-routing the die padframe using photolithographically defined, planar leads to a much larger padframe; this will allow the chip to be integrated with microfluidic networks. Finally, we show a method in which the encapsulant was also used as an optical filter and as a base for integrating more complex structures.

Abstract-This paper reports a novel integrated circuit for fluorescence sensing. The circuit implements a differential readout architecture in order to reduce the overall noise figure. The circuit has been fabricated in a commercially available 0.5 µm CMOS technology. Preliminary results show that the reset noise is reduced by a factor of 1.42 and the readout noise by a factor of 9.20 when the pixel is operated in differential mode versus singleended mode. Spectral responsivity characteristics show that the photodiodes are most sensitive at 480 nm. Using a commercially available emission filter, the sensor was able to reliably detect a concentration of Fura-2 as low as 39 nM. The sensor was used to perform ratiometric measurements and was able to reliably detect a free calcium concentration of 17 nM.

We report an improved design and successful demonstration of single photon avalanche diode (SPAD) detectors fabricated in a standard nwell 0.5 µm CMOS technology.The detectors are implemented as circular junctions between p+ and nwell regions. Two techniques are used to suppress perimeter breakdown: guard rings at the edges of the junctions, formed using lateral diffusion of adjacent nwell regions, and a poly-silicon control gate over the diffused guard rings and surrounding regions. The detectors exhibit a breakdown voltage of -16.85 V, ~4 V higher than simple diode structures in the same technology. The detector exhibits a thermal event rate of 16000 counts/s at room temperature at an excess bias voltage of 1.15 V.