We present a capacitance sensor chip developed in a 0.35 μm CMOS process for monitoring biological cell viability and proliferation. The chip measures cell-to-substrate binding through capacitance-to-frequency conversion with a sensitivity of 590 kHz/fF. In vitro experiments with two human ovarian cancer cell lines (CP70, A2780) were performed and showed the ability to track cell viability in real-time over three days. An imaging platform was developed to provide time-lapse images of the sensor surface, which allowed for concurrent visual and capacitance observation of the cells. Results showed the ability to detect single cell binding events and changes in cell morphology. Image processing was performed to estimate cell coverage of sensor electrodes, showing good linear correlation and providing a sensor gain of 1.28 ± 0.29 aF/μm2, which agrees with values reported in literature. The device is designed for unsupervised operation with minimal packaging requirements. Only a microcontroller is required for readout, making it suitable for applications outside the traditional laboratory setting.
B. Senevirathna, S. Lu, M. Dandin, J. Basile, E. Smela, and P. Abshire, “High resolution monitoring of chemotherapeutic agent potency in cancer cells using a CMOS capacitance biosensor,” Biosensors and Bioelectronics, vol. 142, p. 111501, Oct. 2019. [Online Article]
Monitoring cell viability and proliferation in real-time provides a more comprehensive picture of the changes cells undergo during their lifecycle than can be achieved using traditional end-point assays. Particularly for drug screening applications, high-temporal resolution cell viability data could inform decisions on drug application protocols that might lead to better treatment outcomes. We describe a CMOS biosensor that monitors cell viability through high-resolution capacitance measurements of cell adhesion quality. The system consists of a 3 × 3 mm2 chip with an array of 16 sensors, on-chip digitization, and serial data output that can be interfaced with inexpensive off-the-shelf components. An imaging system was developed to provide ground-truth data of cell coverage concurrently with data recordings. Results showed the sensor's ability to detect single-cell binding events, track cell morphology changes, and monitor cell motility. A chemotherapeutic assay was conducted to examine dose-dependent cytotoxic effects on drug-resistant and drug-sensitive cancer cell lines. Concentrations higher than 5 μM elicited cytotoxic effects on both cell lines, while a dose of 1 μM allowed discrimination of the two cell types. The system demonstrates the use of real-time capacitance measurements as a proof-of-concept tool that has potential to hasten the drug development process.
B. Senevirathna, S. Lu, M. Dandin, J. Basile, E. Smela, and P. Abshire, “Real-time measurements of cell proliferation using a lab-on-CMOS capacitance sensor array,” IEEE Trans. Biomed. Circuits Syst., vol. 12, no. 3, pp. 510–520, Jun. 2018. [Online Article]
We describe a capacitance sensor array that has been incorporated into a lab-on-CMOS system for applications in monitoring cell viability. This paper presents analyticalmodels, calibration results, and measured experimental results of the biosensor. The sensor has been characterized and exhibits a sensitivity of 590 kHz/fF. We report results from benchtop tests and in vitro experiments demonstrating on-chip tracking of cell adhesion as well as monitoring of cell viability. Human ovarian cancer cells were cultured on chip, and measured capacitance responses were validated by comparison with images from photomicrographs of the chip surface. Analysis was performed to quantify cell proliferation and adhesion, and responses to live cells were estimated to be 100 aF/cell.
M. Dandin, M. Habib, B. Nouri, P. Abshire, and N. McFarlane, “Characterization of single-photon avalanche diodes in a 0.5 μm standard CMOS process—Part 2: Equivalent circuit model and Geiger mode readout,” IEEE Sens. J., vol. 16, no. 9, pp. 3075–3083, May 2016. [Online Article]
This article features a model that allows the design and simulation of perimeter-gated single photon avalanche diodes. The model enables both Geiger mode and DC mode simulations. The key parameters of the model were extracted from measured characteristics of a perimeter-gated single-photon avalanche diode fabricated in a 3-metal, 2-poly, single well CMOS process. The article also features a survey of state-of-the-art SPAD models. And, lastly, the article describes the design and measured characteristics of a pixel that includes a perimeter-gated single-photon avalanche diode and a mixed-signal readout circuit.
M. Dandin and P. Abshire, “High signal-to-noise ratio avalanche photodiodes with perimeter field gate and active readout,” IEEE Electron Device Lett., vol. 33, no. 4, pp. 570–572, Apr. 2012. [Online Article]
This letter describes an avalanche photodiode (APD) fabricated in a 0.5-µm CMOS process. In Geiger mode, the APD had an area-normalized dark count rate as low as 2 Hz/µm2 at room temperature. Its signal-to-noise ratio (SNR) increased by an order of magnitude as a result of perimeter field gating. We demonstrate that under high-illumination conditions, perimeter field gating maximizes SNR, whereas under low-light conditions, it maximizes sensitivity.
M. Dandin, P. Abshire, and E. Smela, “Polymer filters for ultraviolet-excited integrated fluorescence sensing,” J. Micromechanics Microengineering, vol. 22, no. 9, p. 095018, Sep. 2012. [Online Article]
Optical filters for blocking ultraviolet (UV) light were fabricated by doping various polymer hosts with a UV absorbing chromophore. The polymers were polydimethylsiloxane (PDMS), a silicone elastomer frequently used in microfluidics, SU-8, a photopatternable epoxy, and Humiseal 1B66, an acrylic coating used for moisture protection of integrated circuits. The chromophore was 2-(2′-hydroxy-5′-methylphenyl) benzotriazole (BTA), which has a high extinction coefficient between 300 nm and 400 nm. We demonstrate filters 5 μm thick that exhibit high ultraviolet rejection (nearly −40 dB at 342 nm) yet pass visible light (near 0 dB above 400 nm), making them ideal for ultraviolet-excited fluorescence sensing within microsystems. The absorbance of the BTA depended on the host polymer. These filters are promising for integrated fluorescence spectroscopy in bioanalytical platforms because they can be patterned by dry etching, molding or exposure to ultraviolet light.
A. Akturk, M. Dandin, A. Vert, S. Soloviev, P. Sandvik, S. Potbhare, N. Goldsman, and P. Abshire, “Silicon Carbide ultraviolet photodetector modeling, design and experiments,” Mater. Sci. Forum, vols. 717-720, pp. 1199-1202, May 2012. [Online Article]
We report measurements and modeling of silicon carbide (SiC) based ultraviolet photodetectors for the detection of light in the mid-to-short ultraviolet range where SiC’s absorption coefficients are high and the corresponding penetration depths are low. These large absorption coefficients result in increased susceptibility of photo-generated electron and holes to surface recombination and therefore give rise to lower quantum efficiencies. To increase responsivity and extend the detection capability of these photodetectors to short ultraviolet wavelengths (or UVC), we measure an existing silicon carbide avalanche photodiode (APD) designed and fabricated for 280 nm operation by General Electric Global Research Center, and then develop models and techniques to increase their operation range to lower UV wavelengths. The measurements aid the development and calibration of a silicon carbide modeling and design suite that is currently being used to assist the design of a new silicon carbide APD for UVC detection. Here the design considerations require low operating voltages, low noise, low dark count rate and high responsivity. We plan to satisfy design criteria by engineering thickness and doping of stacked layers as well as by designing an APD surface that gives rise to minimal recombination of electrons and holes generated by the incident light.
M. Dandin, A. Akturk, B. Nouri, N. Goldsman, and P. Abshire, “Characterization of single-photon avalanche diodes in a 0.5 μm standard CMOS process—Part 1: Perimeter breakdown suppression,” IEEE Sens. J., vol. 10, no. 11, pp. 1682 – 1690, Nov. 2010. [Online Article]
We report on the breakdown characteristics of a single-photon avalanche diode structure fabricated in a 0.5 μm single-well CMOS process. This paper features two mechanisms for reducing perimeter breakdown. The first mechanism consists of using the lateral diffusion of adjacent n-wells to reduce the electric field at the diode's periphery, and the second makes use of a poly-silicon gate over the high field regions to modulate the electric field. We studied each technique independently as well as their combined effect on the devices' avalanche profiles. In addition to marked alterations in the current-voltage curves near and above breakdown, the diodes' breakdown voltages were increased by more than 4 V, indicating that perimeter breakdown was curtailed. We verified this assertion through a self-consistently solved 2-D numerical model based on Poisson's equation and the hole and electron current continuity equations coupled with rate equations for carrier generation due to impact ionization. The model revealed spatial maxima of the charge generation rates, thereby indicating regions susceptible to breakdown. Our investigation revealed that in native diodes, the generation rate peaked at the perimeter and near the junction's surface, suggesting perimeter breakdown. Conversely, in devices where suppression techniques were used, the region of maximum generation spread laterally and away from the surface, indicating full volumetric breakdown was achieved.
N. Nelson, D. Sander, M. Dandin, S. B. Prakash, A. Sarje, and P. Abshire, “Handheld fluorometers for lab-on-a-chip applications,” IEEE Trans. Biomed. Circuits Syst., vol. 3, no. 2, pp. 97–107, Apr. 2009. [Online Article]
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 μV, 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.
M. Dandin, P. Abshire, and E. Smela, “Optical filtering technologies for integrated fluorescence sensors,”Lab Chip, vol. 7, no. 8, p. 955, Jul. 2007. [Online Article]
Numerous approaches have been taken to miniaturizing fluorescence sensing, which is a key capability for micro-total-analysis systems. This critical, comprehensive review focuses on the optical hardware required to attenuate excitation light while transmitting fluorescence. It summarizes, evaluates, and compares the various technologies, including filtering approaches such as interference filters and absorption filters and filterless approaches such as multicolor sensors and light-guiding elements. It presents the physical principles behind the different architectures, the state-of-the-art micro-fluorometers and how they were microfabricated, and their performance metrics. Promising technologies that have not yet been integrated are also described. This information will permit the identification of methods that meet particular design requirements, from both performance and integration perspectives, and the recognition of the remaining technological challenges. Finally, a set of performance metrics are proposed for evaluating and reporting spectral discrimination characteristics of integrated devices in order to promote side-by-side comparisons among diverse technologies and, ultimately, to facilitate optimized designs of micro-fluorometers for specific applications.
“Fail often to succeed sooner” is a common mantra that we are told is the secret to success. When reporting research results, however, scholars rarely write about their failed attempts and only focus on the successful ones. Perhaps the source of this disconnect between what we preach and what we do can be found in the underlying assumption that published work is meant to move the field forward and failed attempts supposedly do not. The goal of the confessions presented in this paper is to show that even failed attempts are genuine and valuable contributions to our field provided that we learn from our mistakes and correct them. The 27 confessions span from planning oversights, digital and analog design errors, misunderstanding of devices, overlooked parasitics, LVS errors, and troubles in testing.
B. Senevirathna, S. Lu, N. Renegar, M. Dandin, E. Smela, and P. Abshire, “System-on-a-chip for automated cell assays using a lab-on-CMOS platform,” in 2019 IEEE International Symposium on Circuits and Systems (ISCAS), 2019, pp. 1-5. [Online Article]
We describe a capacitance sensor system-on-chip that has been incorporated into a lab-on-CMOS system for applications in monitoring cell viability. This paper presents system-level improvements to a capacitance sensor array that include programmable gain, active pixel settings, and serial bus addresses, while at the same time minimizing external bonding requirements towards developing a point-of-care device. Results from benchtop experiments are presented using dry flour to mimic for cell coverage, and show a change of up to 35 kHz. Estimation of electrode coverage is obtained using concurrent time-lapse imaging of the sensor surface which is then correlated to the sensor readings.
S. Lu, B. Senevirathna, M. Dandin, E. Smela, and P. Abshire, “System integration of IC chips for lab-on-CMOS applications,” in 2018 IEEE International Symposium on Circuits and Systems (ISCAS), 2018, pp. 1–5. [Online Article]
Integrating CMOS sensor chips to allow for wet experimentation on lab-on-CMOS devices is a challenging task. In this paper we describe a chip packaging method that will allow for simple integration and handling of small integrated circuit (IC) chips. A chip is embedded in an epoxy handle wafer to allow for photolithographic processing. Electrical connections are provided by a sputter-deposited copper layer and an electroplated nickel layer. Passivation was performed using a second epoxy layer. The process was evaluated by packaging a capacitance sensor chip and performing live cell culture experiments with package cleaning and reuse. Results showed good structural reliability in three repeated experiments over five cumulative days, with no adverse effects on the viability of cells.
T. A. Wood and M. Dandin, “Cybersecurity and the electric grid: Innovation and intellectual property,” in 2017 IEEE International Symposium on Circuits and Systems (ISCAS), 2017, pp. 1–1. [Online Article]
Cybersecurity, as it relates to hardware for the electric grid and to novel smart grid technologies, is an important component of the innovation cycle. We will explore intellectual property strategies that may promote entrepreneurial activities and spur innovations that reduce the electric grid's current vulnerabilities. We will identify areas in which stakeholders such as U.S. policy makers, the United States Patent and Trademark Office (USPTO), the business community, and the academic community, can collaborate to foster growth and innovation.
M. Dandin and P. Abshire, “Near breakdown spectral responsivity of perimeter-gated single-photon avalanche diodes,” in 2017 IEEE 60th International Midwest Symposium on Circuits and Systems (MWSCAS), 2017, pp. 867–870. [Online Article]
This paper investigates the near-breakdown spectral responsivity of perimeter-gated single-photon avalanche diodes (SPADs). We report, for the first time, the effects of perimeter gating on spectral responsivity. Further, we describe a detailed experimental procedure for measuring spectral response. Our investigation reveals that perimeter gating strongly influences spectral responsivity by broadening the response over the visible range, confirming that perimeter gating activates the volumetric junction of the measured devices.
B. Senevirathna, A. Castro, M. Dandin, E. Smela, and P. Abshire, “Lab-on-CMOS capacitance sensor array for real-time cell viability measurements with I2C readout,” in 2016 IEEE International Symposium on Circuits and Systems (ISCAS), 2016, pp. 2863–2866. [Online Article]
Capacitance sensing is an emerging technology for monitoring cell viability. This work extends a previously developed sensor that measured capacitive loading by cells on the oscillation frequency of a current-starved ring oscillator and converted the frequency to a digital value by counting oscillation cycles. The new sensor array has been developed into a one-chip lab-on-CMOS system with integrated temperature sensors, serial readout to an external microcontroller using an Inter-Integrated Circuit (I2C) bus, and automatic scanning to allow for autonomous data collection. To allow sensing at the required aF levels, the system was realized on single chip to reduce the baseline capacitance, and long counting times were employed. The I2C module was moved to the edge of the chip prevent exposing cells to unacceptably high temperatures during viability studies.
B. Nouri, M. Dandin, and P. Abshire, “Large-area low-noise single-photon avalanche diodes in standard CMOS,” in 2012 IEEE Sensors, 2012, pp. 1–5. [Online Article]
We report a Single Photon Avalanche Diode (SPAD) in standard CMOS with a physical implementation that offers high fill factor and very low Dark Count Rate (DCR). The demonstrated suppression of the Dark Count is achieved through alterations made to the structure of the SPAD without any modifications in the fabrication process. The structure of the device consists of a perimeter gated junction with a geometrical profile that is tailored for high gettering efficiency. We previously demonstrated DCR of 20 KHz for a 50 μm diameter perimeter gated circular SPAD (2 orders of magnitude DCR reduction). Using our current design we report DCRs of 10 Hz for a 1200 μm 2 SPAD operated at an excess bias of up to 1V. The reported DCRs are obtained for SPADs fabricated in single-well standard CMOS and operated at room temperature.
P. Abshire, A. Bermak, R. Berner, G. Cauwenberghs, S. Chen, J. B. Christen, T. Constandinou, E. Culurciello, M. Dandin, T. Datta, T. Delbruck, P. Dudek, A. Eftekhar, R. Etienne-Cummings, G. Indiveri, M. K. Law, B. Linares-Barranco, J. Tapson, W. Tang, Y. Zhai, “Confession session: learning from others’ mistakes,” in 2011 IEEE International Symposium of Circuits and Systems (ISCAS), 2011, pp. 1149–1162. [Online Article]
People rarely put in their papers the things that didn't work, the mistakes they made, and how they found out what went wrong. Such confessions can help others learn how to avoid similar mistakes. Twenty-six confessions were collected to form the bulk of this paper. Themes that arise are errors that result from not understanding the limitations of simulation tools in modeling physical reality, chip verification errors that result from lack of clear communication between designers, and projects that are considered in their own isolated environment of technical challenges rather than the broader context of their environment or application.
M. Dandin, A. Akturk, A. Vert, S. Soloviev, P. Sandvik, S. Potbhare, N. Goldsman, P. Abshire, and K. P. Cheung, “Optoelectronic characterization of 4H-SiC avalanche photodiodes operated in DC and in Geiger mode,” in 2011 IEEE International Semiconductor Device Research Symposium (ISDRS), 2011, pp. 1–2. [Online Article]
Silicon carbide has attracted a lot interest in the power electronics arena due to its advantageous properties over other semiconductor materials; it has high thermal conductivity, a wide bandgap, and a high breakdown electric field, all of which are properties that make it suitable for high voltage and high current density devices capable of operating in extremely harsh environments. Another noted advantage of SiC is its capability to transduce photons in the ultraviolet band of the electromagnetic spectrum. Due to the large energy gap, SiC p-n junctions exhibit high UV responsivity and negligible response beyond 400 nm. This makes SiC ideal for solar-blind UV imaging, and as a result there has been significant efforts towards optimizing the performance of SiC avalanche photodiodes (APDs).
B. Nouri†, M. Dandin†, and P. Abshire, “Characterization of single-photon avalanche diodes in standard CMOS,” in 2009 IEEE Sensors, 2009, pp. 1889–1892. (†Contributed equally.) [Online Article]
We report experimental results from a single-photon avalanche diode (SPAD) structure fabricated in a standard 0.5 μm single-well CMOS process. The diode consists of a p+/n-well junction, and its multiplication region is surrounded by a diffused guard-ring obtained through lateral diffusion of closely spaced n-wells. Moreover, a poly-silicon gate is placed over the junction's perimeter. These mechanisms help in curtailing perimeter breakdown, as has been previously reported. In this work, we study their combined effect on the junction's breakdown voltage, and on the dark count rate when the avalanche diode is operated in Geiger mode. Our results show that the poly-silicon gate and the diffused guard ring both increase the breakdown voltage with roughly similar efficacy. Furthermore, our results reveal that the dark count rate (DCR) is reduced by a factor of 7 when the gate potential is decreased below -16 V, indicating that the surface regions depleted by the field not only help in preventing edge breakdown but also contribute in reducing the device's noise floor.
A. Akturk, M. Dandin, N. Goldsman, and P. Abshire, “Modeling of perimeter-gated silicon avalanche diodes fabricated in a standard single-well CMOS process,” in 2009 IEEE International Semiconductor Device Research Symposium (ISDRS), 2009, pp. 1–2. [Online Article]
We investigate the design, fabrication and numerical modeling details of a silicon impact ionization device that was implemented in a standard single-well CMOS process line for use in biomedical applications. Device performance modeling of the perimeter-gated silicon avalanche diode is presented. To lower dark current, tune the current multiplication rate, and change the breakdown voltage, two techniques were develop: First is laying out n-wells close to each other to favorably increase spatial aliasing of diffused dopants, and second is using a gate terminal at the perimeter to modify electric field in the vicinity of the p+-n junction. Results verified by calculations and simulations show that the device can be operated in photon-counter mode with high breakdown voltages and sharp current transitions or in current multiplication mode as in solid-state impact ionization multipliers.
M. Dandin, I. D. Jung, M. Piyasena, J. Gallagher, N. Nelson, M. Urdaneta, C. Artis, P. Abshire, and E. Smela, “Post-CMOS packaging methods for integrated biosensors,” in 2009 IEEE Sensors, 2009, pp. 795–798. [Online Article]
We report on several techniques that have been pursued in our laboratories for packaging complementary metal-oxide semiconductor (CMOS) sensors for use in biological environments, such as cell medium. These techniques are suited for single CMOS die ranging from 1.5 × 1.5 mm2 to 3 × 3 mm2 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.
N. Nelson, D. Sander, M. Dandin, A. Sarje, S. B. Prakash, H. Ji, and P. Abshire, “A handheld fluorometer for measuring cellular metabolism,” in 2008 IEEE International Symposium on Circuits and Systems (ISCAS), 2008, pp. 1080–1083. [Online Article]
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.
I. Weinberg, P. Y. Stepanov, A. S. Weinberg, P. Abshire, and M. Dandin, “Improvement of energy resolution in Geiger-mode APD arrays using curve-fitting of signal decay,” in 2008 IEEE Nuclear Science Symposium (IEEE NSS), 2008, pp. 1416–1418. [Online Article]
A method is presented to improve the energy resolution of scintillators read out with Geiger-mode avalanche photodiode arrays. The method employs digital signal processing, in which individual decay curves for gamma-ray detection events are digitized and then fitted to analytical functions whose amplitude provides energy information. Simulation studies suggest that after-pulses represent the largest source of energy resolution loss, which can be improved with curve-fitting. An experimental measurement confirmed that energy resolution could be improved with least-square curve-fits to a simple exponential model.
I. Weinberg, P. Stepanov, P. Abshire, D. Sander, A. Weinberg, and M. Dandin, “Improving SNR of radiation detector readout electronics,” J. Nucl. Med., vol. 49, no. S1, p. 408P, May 2008. (Abstract only.) [Online Article]
Objectives: Solid-state radiation detectors have advantages of size and low voltage, but often suffer from noise artifacts. We sought to develop flexible readout methods to improve signal-to-noise ratio (SNR) for such detectors.
Methods: Readout strategies were evaluated for increasing signal-to-noise ratios in circuits intended for active-pixel-sensor (APS) detectors (e.g., as in Medipix arrays). An additional amplifier element was inserted into the traditional three-transistor integration circuit, in order to decouple the intrinsic capacitance of the radiation detector from the charging capacitor. SNR from the resulting circuit was compared to traditional APS integrating circuits during exposure to x-rays with 75-keV peak energy.
Results: Experimental measurements demonstrated approximately ten-fold improvement in SNR for the four-transistor integration circuit as compared to traditional APS systems.
Conclusions: Signal-to-noise ratio for solid-state radiation detectors can be improved through additional pixel-based amplifier stages.
N. Nelson, S. Prakash, D. Sander, M. Dandin, A. Sarje, H. Ji, and P. Abshire, “A handheld fluorometer for UV excitable fluorescence assays,” in 2007 IEEE Biomedical Circuits and Systems Conference (BIOCAS), 2007, pp. 111–114. [Online Article]
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 μM 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.
E. Smela, M. Christophersen, S. Prakash, M. Urdaneta, M. Dandin, and P. Abshire, “Integrated cell-based sensors and cell clinics utilizing conjugated polymer actuators,” in 2007 SPIE Smart Structures and Materials: Electroactive Polymer Actuators and Devices (EAPAD), 2007, p. 65240G. [Online Article]
Cell-based sensors are being developed to harness the specificity and sensitivity of biological systems for sensing applications, from odor detection to pathogen classification. These integrated systems consist of CMOS chips containing sensors and circuitry onto which microstructures have been fabricated to transport, contain, and nurture the cells. The structures for confining the cells are micro-vials that can be opened and closed using polypyrrole bilayer actuators. The system integration issues and advances involved in the fabrication and operation of the actuators are described.
D. Sander, M. Dandin, H. Ji, N. Nelson, and P. A. Abshire, “Low-noise CMOS fluorescence sensor,” in 2007 IEEE International Symposium on Circuits and Systems (ISCAS), 2007, pp. 2007–2010. [Online Article]
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 μ m 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.
I. Weinberg, P. Cheng, K. H. Wong, K. Cleary, P. Abshire, V. Saveliev, M. Dandin, L. G. Gruionu, “PET-enabled glove for molecular image-guided surgery,” J. Nucl. Med., vol. 48, no. S2, p. 163P, 2007. (Abstract only.) [Online Article]
Objectives: Pre-surgical assessments are of limited benefit when the anatomy is likely to change as a result of interventional procedures. Non-imaging assessments (i.e., probes) are useful in high-contrast surgical cases (e.g., sentinel nodes), but are less useful in discriminating tumor from background tissues. We sought a technical solution capable of providing molecular images to surgeons in real-time, and with OR-friendly properties: low voltage, intuitive registration to features within the operative site, and single-use application. Methods: Compact PET detector assemblies were mounted on three fingers of an operator’s hand. Each PET detector assembly consists of two-dimensional arrays of Cerium-doped LuAG pillars (Crytur Inc., Czech Republic) mounted on quantum photodetectors (“silicon photomultipliers”) biased at approximately 35 volts. Electromagnetic position sensors are embedded in the PET detector assemblies, and read out with a motion tracking system (Northern Digital Incorporated, Waterloo, ON). Data is acquired with sampling analog-to-digital converters (National Instruments, Austin, TX), and displayed using a graphical user interface (GUI) based on the Georgetown Image Guided Surgery Toolkit, which shows PET findings superimposed on a representation of the surgeon’s fingers. Results: Simulations showed that small structures in the volume subtended by the fingers would be visualized with high contrast. Experimentally, the LuAG/APD PET detectors 511 keV photopeak showed no measurable effect due to the electromagnetic pulses from the motion tracker. Conclusions: We present a new paradigm for surgical visualization, consisting of finger-mounted PET detectors, in which a model of the surgeon’s own fingers with superimposed PET findings serves as an intuitive registration tool. The low component cost suggests that single-use application (i.e., as a disposable PET glove) is feasible.
M. Dandin, N. M. Nelson, H. Ji, and P. Abshire, “Single-photon avalanche detectors in standard CMOS,” in 2007 IEEE Sensors, 2007, pp. 585–588. [Online Article]
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.
H. Ji, M. Dandin, P. Abshire, and E. Smela, “Integrated fluorescence sensing for lab-on-a-chip devices,” in 2006 IEEE/NLM Life Science Systems and Applications Workshop, 2006, pp. 1–2. [Online Article]
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
M. Dandin, “Silicon photomultiplier with in-microcell adaptation mechanism,” United States Provisional Patent Application No. 62/638,135, filed Mar. 3, 2018.
M. Dandin, “Delay circuit with dual delay resolution regime,” United States Patent Application No. 15/496,924, filed Apr. 25, 2017.
M. Dandin, “Single-photon avalanche diode circuit with variable hold-off time and dual delay regime,” United States Patent No. 9,671,284, issued Jun. 6, 2017.
M. Dandin, “Circuit and method for locally controlling breakdown voltage and performance in a silicon photomultiplier array,” United States Provisional Patent Application No. 62/435,586, filed Dec. 16, 2016.
M. Dandin, “Programmable delay cell and delay line, and readout circuit including the same,” United States Provisional Patent Application No. 62/278,585, filedJan. 14, 2016.