Honghao Ji

Contact Imaging: Simulation and Experiment

We report simulated and experimental image quality for contact imaging, a method for imaging objects close to the sensor surface without intervening optics. This technique preserves microscale resolution for applications that can not tolerate the size or weight of conventional optical elements. In order to assess image quality, we investigated the spatial resolution of contact imaging, which depends on the sensor size as well as the distance between objects and the sensor surface. We studied how this distance affects image quality using a commercial optical simulator. Simulation results show that the image quality degrades as objects move away from the sensor surface. To experimentally validate these results, an image sensor was designed and fabricated in a commercially available three metal, two poly, 0.5 mum CMOS technology. Experiments with the contact imager corroborate the simulation results. Two specific applications of contact imaging are demonstrated.

Low-noise CMOS Fluorescence Sensor

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 mum 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 single-ended 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.

CMOS contact imager for monitoring cultured cells

There is a growing interest in developing low cost, low power, highly integrated biosensor systems to characterize individual cells for applications such as cell analysis, drug development, environmental monitoring, and medicine. In such micro-systems, it is desirable to track individual cells in real time in order to steer cells using on-chip micro-actuators or monitor the movement of motile cells. To address this requirement, we are developing an embedded optical image sensor, called a contact imager, for imaging of a biological specimen directly coupled to the chip surface. The designed CMOS image sensor comprises an array of active pixel sensors (APS), logic and control signal generation, and readout circuits. The pixel layout has a pitch of 8.4 /spl mu/m (24 /spl lambda/). The design was fabricated in a commercially available 0.5 /spl mu/m CMOS technology. The imager was first characterized on the bench as a normal CMOS image sensor, and then as a contact imager with microbeads (16 /spl mu/m) placed directly on the chip surface. After further packaging with bio-compatible material, the chip was tested with cells cultured directly on the chip surface. Test results confirm successful detection of both beads and cells.

Single Photon Avalanche Detectors in Standard CMOS

We report an improved design and successful demonstration of single photon avalanche diode (SPAD) detectors fabricated in a standard nwell 0.5 mum 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.

Integrated Fluorescence Sensing for Lab-on-a-chip Devices

A low noise optical sensor and biocompatible microscale optical filters for integrated fluorescence sensors were developed and tested. The sensor was fabricated in a 0.5 mum CMOS process. The measured reset noise of the sensor is reduced by a factor of 10 compared to conventional active pixel sensors. The transmission ratio in the pass-band and suppression ratio in the stop-band of the optical filters are comparable to that of macroscopic commercial filters for fluorescence microscopy

A CMOS contact imager for locating individual cells

We describe the design of a contact imager for applications in lab-on-a-chip systems, such as sample preparation and manipulation and monitoring of cells. This is a challenging task because most cells are nearly transparent, so the contrast between the presence and absence of a cell is small. Thus additional image processing is necessary to locate cells. To enhance the image contrast and facilitate object recognition, the contact imager implements on-chip one bit quantization with a dynamic threshold that adapts to the background illumination. The imager is capable of locating dark objects in a bright background or bright objects in a dark background. The locations of recognized cells are generated as outputs to alleviate computational requirements for generating control signals in closed-loop systems

A CMOS image sensor for low light applications

We describe and analyze a novel CMOS pixel for high speed, low light imaging applications. The pixel achieves lower dark current and noise and increased gain in comparison with conventional three-transistor, one-photodiode active pixel sensors without sacrificing speed and scalability to large arrays. It accomplishes this by biasing the photodiode of each pixel near zero volts and by separating the photodiode from the floating diffusion integration node. An image sensor with a 256 times 256 array of these pixels was designed for a commercially available 0.18 mum CMOS technology. The pixel size is 5mu.m times 5mum with a fill factor of 31%. The chip area is 3000 mum times 3000mum. 1.8 V and 3.3 V power supplies are used for logic and sensor array, respectively. Differential output and chip level correlated-double sampling are used to suppress fixed pattern noise. Transmission gates with dummy transistors are incorporated into the readout chain to reduce both clock feedthrough and charge injection

A handheld fluorometer for measuring cellular metabolism

We demonstrate the application of a handheld fluorometer optimized for UV excitable assays. We demonstrate the measurement of metabolic products as yeast cells germinate in dextrose solution. In particular we measure NADH which is produced during cellular respiration. The handheld fluorometer consists of a CMOS active pixel sensor with in-pixel CDS, coupled with a custom chromophore-polymer emission Alter and a UV LED as the excitation source. The handheld fluorometer is able to detect as little as 10 muM of NADH, and in its present format should be applicable to any fluorescence assay with UV excitation and visible emission wavelengths.

A Handheld Fluorometer for UV Excitable Fluorescence Assays

We report the development of a handheld fluorometer for UV excitable fluorescence assays. The handheld detector serves as a demonstration platform for an integrated fluorescence sensor and comprises a CMOS detector coated with a polymer based optical filter and placed in close proximity to a UV LED which is used as an excitation source. The sensor function has been validated for metabolic activity and cytotoxicity assays. The fluorometer was able to determine NADH concentration as low as 17 muM and was able to track NADH production in live yeast cells over time and as the yeast cell concentration varied. The sensor was also used to discriminate the viability of human intestinal adenocarcinoma cells (Caco-2 cell line) using a live/dead stain after exposure to toxic and benign nanoparticles. The integrated fluorescence sensor is suitable for microscale fluorescence detection in lab-on-a-chip applications.

A structurally stable realization for Jacobi elliptic functions

By adding convergence terms, the dynamical equations for the generation of elliptic functions versus time are presented. This results in a structurally stable oscillator with limit cycles, which are Jacobi elliptic functions. From these equations a CMOS realization is developed with the nonlinearities obtained by using analog four-quadrant multipliers of the type developed by Kimura (1995).