David Sander

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.

Electron beam and optical proximity effect reduction for nanolithography: New results

Proximity effect correction by dose modulation is widely practiced in electron-beam lithography. Optical proximity control is also possible using a combination of shape adjustment and phase control. Assigning “the right” dose (or fill factor and phase for optics) is a well known mathematical inverse problem. Linear programming, by definition, is the appropriate method for determining dose. In the past, the technique was too slow for full-scale implementation in mask making. Here, the authors discuss how recent developments in computer speed and architecture have improved the prospects for full-scale implementation. In addition, the authors discuss some numerical techniques, analogous to gridding and relaxation, that make linear programming more attractive in mask making.

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

The feeling of color: A haptic feedback device for the visually disabled

We describe a sensory augmentation system designed to provide the visually disabled with a sense of color. Our system consists of a glove with short-range optical color sensors mounted on its fingertips, and a torso-worn belt on which tactors (haptic feedback actuators) are mounted. Each fingertip sensor detects the observed objectpsilas color. This information is encoded to the tactor through vibrations in respective locations and varying modulations. Early results suggest that detection of primary colors is possible with near 100% accuracy and moderate latency, with a minimum amount of training.

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 cell impedance sensor based on a silicon cochlea

In this paper, we present the design of an integrated CMOS sensor for cell impedance measurement. To achieve simultaneous measurements over a wide frequency range, the impedance sensor has been developed using silicon cochleae as both the input stimulus generator and the output frequency analyzer. This solution, inspired by the accuracy and efficiency of biological systems, has several advantages. The silicon cochlea is able to make measurements over a very wide frequency range (from Hz to MHz) with variable resolution. Power consumption of the sensor is below 30μW due to the biasing regime used in the silicon cochleae. Furthermore, the implementation of the sensor is fully autonomous requiring no reference clocks or signal generators, facilitating integration into larger cell analysis systems.

Noise model, analysis and characterization of a differential active pixel sensor

We report the design, analytical model and experimental noise performance from a photo sensor fabricated in a 0.5 mum commercial CMOS process. The sensor is a novel differential active pixel sensor which performs in-pixel correlated double sampling (CDS) to reduce correlated and environmental noise at the expense of increased thermally generated noise sources such as reset and readout noise. In comparison with a representative single ended sensor, the differential sensor exhibits an increased fundamental reset and readout noise of 117% and 58% respectively.

Integration time optimization for integrating photosensors

We maximized the information transmission for an integrating photosensor by optimizing the integration time. As a case study, experimentally determined reset, readout and photocurrent shot noise was used to determine the capacity of a differential active pixel sensor as a function of illumination level and integration time. Experimentally derived data show that the information rate is poor at both small and large integration times, with a maximum information rate occurring between these extremes. This maximum occurs at different integration times for different illumination levels and is used to determine the optimal integration time for the sensor.