Browsing by Author "Chen, Tom, advisor"
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Item Open Access An efficient multi channel, 0.2 nJ/bit transmitter with tuning for process variation for biomedical telemetry in the MedRadio band of 401-457MHz(Colorado State University. Libraries, 2016) Gundla, Abhiram Reddy, author; Chen, Tom, advisor; Collins, George, committee member; Henry, Chuck, committee memberWith the increasing applications of bio-integrated telemetric systems, there is a growing demand for wireless transceivers in these systems to interface with the outside world. The use of wireless transceivers is desirable because they allow complete untethering of medical devices from patients. Applications of the medical devices that have transceivers may include, but not limited to, neuro-prosthetics for stimulation, sensing vital signs, wireless monitoring of neuro chemicals in the brain, wireless endoscopy, and remote medical diagnosis and therapy. The implantable medical devices to introduce impulses to the central nervous system to treat the diseases efficiently and/or to provide relief to pain are usually in the medical implantable communication services band of 401-406 MHz. The spectrum of 401-457 MHz band is called medical device radio communications service (MedRadio) band, was allocated by FCC on secondary basis. There exists various transmitter designs for the MedRadio band aimed at high energy efficiency (i.e. low energy per bit transmitted), as low as 0.16 nJ/bit. A few designs are targeted to work at high dc power transmission efficiency, as high as 22%. But, the existing designs fail to be truly MedRadio-standard complaint with short-comings either in terms of not using all the channels in the MedRadio band, low transmitter efficiency, or low output power emitted. The search for better designs of transmitters that can utilize all the channels with high transmission efficiency and high emitted output power continues. This thesis proposes an efficient multichannel transmitter circuit design in the MedRadio band at 401-457 MHz. The transmitter circuit consists of a multichannel phase locked loop (PLL) with rail to rail quadrature output voltage controlled oscillator (VCO), a low power digital synchronous programmable integer N-divider, bang bang Phase frequency detector (PFD), charge pump and a 3rd order loop filter, a passive mixer and a power amplifier (PA). The VCO of the transmitter is designed to account for process variation. The proposed transmitter uses quadrature phase shift keying (QPSK) modulation scheme to transmit data. The power consumption of the transmitter is 460 µW at the power supply voltage of 1.2 V, and consumes only 0.2 nJ of energy for every bit transmitted in the MedRadio band. The output power emitted by the power amplifier of the transmitter is -10.8 dBm. The transmitter is able to hop through all the 10 channels of 300 kHz bandwidth of each from 402 to 405 MHz, all the 4 channels of 6MHz bandwidth of each from 413 to 457 MHz. The overall global efficiency of the transmitter is 13.9 %. The proposed transmitter meets all the FCC requirements for the MedRadio band. This proposed work is implemented in a 180nm CMOS process. The proposed transmitter working in the MedRadio band consumes only 0.2 nJ/bit compared to 0.65 nJ/bit of the only other MedRadio-band compliant design. The transmitter energy consumption is low at 460 µW and efficiency is high at 13.9% when compared to mW energy consumption and single-digit efficiency achieved by existing designs.Item Open Access Crexens™: an expandable general-purpose electrochemical analyzer(Colorado State University. Libraries, 2019) Yang, Lang, author; Chen, Tom, advisor; Collins, George J., committee member; Wilson, Jesse, committee member; Tobet, Stuart, committee memberElectrochemical analysis has gained a great deal of attention of late due to its low-cost, easy-to-perform, and easy-to-miniaturize, especially in personal health care where accuracy and mobility are key factors to bring diagnostics to patients. According to data from Centers for Medicare & Medicaid Services (CMS) in the US, the share of health expenditure in the US has been kept growing in the past 3 decades and reached 17.9% of its overall Gross Domestic Product till 2016, which is equivalent to $10,348 for every person in the US per year. On the other hand, health care resources are often limited not only in rural area but also appeared in well-developed countries. The urgent need and the lack of health resource brings to front the research interest of Point-of-Care (PoC) diagnosis devices. Electrochemical methods have been largely adopted by chemist and biologist for their research purposes. However, several issues exist within current commercial benchtop instruments for electrochemical measurement. First of all, the current commercial instruments are usually bulky and do not have handheld feature for point-of-care applications and the cost are easily near $5,000 each or above. Secondly, most of the instruments do not have good integration level that can perform different types of electrochemical measurements for different applications. The last but not the least, the existing generic benchtops instruments for electrochemical measurements have complex operational procedures that require users to have a sufficient biochemistry and electrochemistry background to operate them correctly. The proposed Crexens™ analyzer platform is aimed to present an affordable electrochemical analyzerwhile achieving comparable performance to the existing commercial instruments, thus, making general electrochemical measurement applications accessible to general public. In this dissertation, the overall Crexens™ electrochemical analyzer architecture and its evolution are presented. The foundation of the Crexens™ architecture was derived from two separate but related research in electrochemical sensing. One of them is a microelectrode sensor array using CMOS for neurotransmitter sensing; the other one is a DNA affinity-based capacitive sensor for infectious disease, such as ZIKA. The CMOS microelectrode sensor array achieved a 320uM sensitivity for norepinephrine, whereas the capacitive sensor achieved a dynamic range of detection from 1 /uL to 105 /uL target molecules (20 to 2 million targets), which makes it be within the detection range in a typical clinical application environment. This dissertation also covers the design details of the CMOS microelectrode array sensor and the capacitive sensor design as a prelude to the development of the Crexens™ analyzer architecture. Finally, an expandable integrated electrochemical analyzer architecture (Crexens™) has been designed for mobile point-of-care (POC) applications. Electrochemical methods have been explored in detecting various bio-molecules such as glucose, lactate, protein, DNA, neurotransmitter, steroid hormone, which resulted in good sensitivity and selectivity. The proposed system is capable of running electrochemical experiments including cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), electrochemical capacitive spectroscopy (ECS), amperometry, potentiometry, and other derived electrochemical based tests. This system consist of a front-end interface to sensor electrodes, a back-end user interface on smart phone and PC, a base unit as master module, a low-noise add-on module, a high-speed add-on module, and a multi-channel add-on module. The architecture allows LEGO™-like capability to stack add-on modules on to the base-unit for performance enhancements in noise, speed or parallelism. The analyzer is capable of performing up to 1900 V/s CV with 10 mV step, up to 12 kHz EIS scan range and a limit of detection at 637 pA for amperometric applications with the base module. With high performance module, the EIS scan range can be extended upto 5 MHz. The limit of detection can be further improved to be at 333 fA using the low-noise module. The form factor of the electrochemical analyzer is designed for its mobile/point-of-care applications, integrating its entire functionality on to a 70 cm² area of surface space. A glutamine enzymatic sensor was used to valid the capability of the proposed electrochemical analyzer and turned out to give good linearity and reached a limit of detection at 50 uM.Item Open Access Design of a multi-sensor platform for integrating extracellular acidification rate with multi-metabolite flux measurement for small biological samples(Colorado State University. Libraries, 2019) Obeidat, Yusra M., author; Chen, Tom, advisor; Pasricha, Sudeep, committee member; Collins, George, committee member; Tobet, Stuart, committee memberTo view the abstract, please see the full text of the document.Item Open Access Development of electrochemical assays and biosensors for detection of Zika virus(Colorado State University. Libraries, 2019) Filer, Jessica, author; Geiss, Brian, advisor; Chen, Tom, advisor; Henry, Charles, committee member; Wilusz, Jeff, committee member; Ebel, Greg, committee memberZika virus (ZIKV) emerged as a significant public health concern after the 2015-2016 outbreak in South and Central America. Severe neurological complications and birth defects in adults and children respectively underscore the need for quick and accurate diagnosis so that proper medical observation and intervention can be done. Electrochemical assays and biosensors are attractive as alternative diagnostic tools due to their sensitivity and ease of miniaturization. This dissertation describes three novel electrochemical assays and biosensors to detect ZIKV specific nucleic acid, antibodies, and virus particles. A nuclease protection ELISA (NP-ELISA) was developed for nucleic acid detection by enzymatic readout. The assay was validated using synthetic complementary oligos for absorbance, chemiluminescence, and electrochemical enzymatic readout. Two horseradish peroxidase substrates, 3,3',5,5'-Tetramethylbenzidine (TMB) and hydroquinone, were characterized electrochemically and compared for electrochemical assay use. Electrochemical TMB readout demonstrated better sensitivity compared to all tested detection modalities with a limit of detection of 3.72×103 molecules mL-1, which compares well to the amount of ZIKV RNA in clinical samples and to other approved assays like the CDC's Trioplex assay. For serological analysis, a capacitive microwire biosensor was developed and validated using immunized mouse sera to detect a ZIKV antibody response. Measurements were taken through a wide serial dilution range of 1:1018 to 1:103 and two dilutions (1:1012 and 1:106) were used for analysis for optimal sensitivity. A statistically significant immune response was detected four days after immunization at a 1:1012 dilution and was specific for ZIKV when compared with Chikungunya virus (CHIKV). These results indicate that serological analysis can be performed four days earlier with the wire sensor compared to ELISAs using ultra-dilute samples. The sensor also was used to differentiate between IgG and IgM antibodies and compared well with ELISA results. Lastly, an impedance array sensor was designed and validated for detection of ZIKV particles. The array allows for simultaneous handling of many electrodes, which increases throughput compared to other biosensor designs. The sensor demonstrated good sensitivity with an LOD of 22.4 focus forming units (FFU) which compares well to other reported sensors. In addition, it was optimized for specificity and tested using Sindbis virus (SINV) as a negative control. These novel platforms comprise new advancements in biosensor technology by simplifying existing assays, increasing sensitivity, and providing a new platform for handheld measurements.Item Open Access Low power biosensor and decimator design(Colorado State University. Libraries, 2013) Scholfield, Kristin, author; Chen, Tom, advisor; Collins, George, committee member; Tobet, Stuart, committee memberThis paper examines the use of low power circuits applied to biosensors used to observe neurotransmission. The term "biosensors" in the broadest sense describes many devices which are used to measure a biological state e.g. neural signal acquisition. The methods for developing biosensors are just as diverse, but one common thread is that many biomedical devices are battery operated and require low power for mobility. As biosensors become more complex they also require more functions such as data storage, digital signal processing, RF transmission etc. The more functions a sensor needs, the tighter the constraint for power consumption on a battery operated device becomes. In order to solve this problem, biosensors are increasingly being designed for low power consumption while weighing tradeoffs for performance and noise. Designers accomplish this by lowering the supply voltage, which reduces the overall size, and thus the load, of the devices. The amount of individual components will also be reduced, allowing for a smaller, faster device. Biosensors are important because they grant the ability for scientists to better understand complex biological systems. While many other methods exist for observing biological systems, electrochemistry is a practical method for measuring redox reaction because it senses chemical reactions on the surface of an electrode. The reaction will create a current, which can be interpreted via electronics. With the use of electrochemistry, scientist can cheaply and practically observe changes occurring between cells. On the engineering side, modern silicon processes provide small, tightly packed microelectrodes for high spatial resolution. This allows scientists to detect minute changes over a small spatial range. With an array of electrodes on the scale of 1000s, electrochemistry can be used to record data from a sizable cellular sample. Such an array could be used to identify several biological functions such as communication between cells. By combining known electrochemistry methods with low power circuit designs, we can create a biosensor that can further advance the understanding of the operation of cells, such as neurotransmission. The goal of our project is to create a device that uses electrochemistry to detect a redox reaction between a chemical, such as nitric oxide, and an electrode. The device needs to be battery operated for mobility and it must contain all needed electronics on chip, including amplification, digital signal processing, data transmission etc. This requires a surface of electrodes on chip that can handle the environment needed for a living tissue such as: specific temperature, pH and humidity. In addition, it requires a chip that is low power and which produces little heat. This thesis describes two separate designs, both of which are part of a final biosensor design that will be used for the detection of nitric oxide. The first design is a biosensor microelectrode array. The array will be used along with electrochemistry to detect the release of nitric oxide from a living tissue sample. The electrodes are connected to a chain of electronics for on chip signal processing. The design runs at a voltage of 3V in a 0.6µm CMOS process. The final layout for the microelectrodes measured approximately 4.84mm2 with a total of 8,192 electrodes and consumed 0.310mW/channel. The second design is a low power decimator for a sigma-delta analog to digital converter designed for biomedical applications. The ADC will be used along with a chain of amplifying electronics to interpret the signals received from the microelectrode array. The design runs at a voltage of 0.9V in a 0.18µm CMOS process. Its final layout measured approximately 0.0158mm2 and consumed 3.3uW of power. The ADC and microelectrode array were designed and fabricated separately to ensure their validity as standalone designs.Item Open Access Low-noise, low-power transimpedance amplifier for integrated electrochemical biosensor applications(Colorado State University. Libraries, 2014) Wilson, William, author; Chen, Tom, advisor; Pezeshki, Ali, committee member; Henry, Chuck, committee memberBiosensor devices have found an increasingly broad range of applications including clinical, biological, and even pharmaceutical research and testing. These devices are useful for detecting chemical compounds in solutions and tissues. Current visual or optical methods include fluorescence and bio/chemiluminescence based detection. These methods involve adding luminescent dyes or fluorescent tags to cells or tissue samples to track movement in response to a stimulus. These methods often harm living tissue and interfere with natural cell movement and function. Electrochemical biosensing methods may be used without adding potentially harmful dyes or chemicals to living tissues. Electrochemical sensing may be used, on the condition that the desired analyte is electrochemically active, and with the assumption that other compounds present are not electrochemically active at the reduction or oxidation potential of the desired analyte. A wide range of analytes can be selectively detected by specifically setting the potential of the solution using a potentiostat. The resulting small-magnitude current must then be converted to a measurable voltage and read using a low-noise transimpedance amplifier. To provide spatial resolution on the intra-cellular level, a large number of electrodes must be used. To measure electrochemical signals in parallel, each electrode requires a minimum of a transimpedance amplifier, as well as other supporting circuitry. Low power consumption is a requirement for the circuitry to avoid generating large amounts of heat, and small size is necessary to limit silicon area. This thesis proposes the design of a low-noise, low-power transimpedance amplifier for application in integrated electrochemical biosensor devices. The final proposed design achieves a 5MΩ transimpedance gain with 981aA/√Hz input inferred noise, 8.06µW at 0.9V power supply, and occupies a silicon area of 0.0074mm2 in a commercial 0.18µm CMOS process. This thesis also explores the development of a multi-channel electrochemical measurement system.Item Open Access Low-power switched-capcitor amplifier and Sigma-Delta modulator design for integrated biosensor applications(Colorado State University. Libraries, 2013) Selby, Ryan, author; Chen, Tom, advisor; Collins, George, committee member; Tobet, Stuart, committee memberNeurotransmitters are chemicals present in living tissue which regulate biological functions. Some neurotransmitters which are present in the brain, such as nitric oxide (NO), are believed to play a role in the process of cellular migration during development. Today there is no practical way to measure gradients of neurotransmitters across pieces of tissue in both the spatial and temporal domains. Single electrode systems can be used to determine neurotransmitter concentrations at specific locations, but do not provide spatial resolution. Dyes and marking compounds can be used to locate concentrations of neurotransmitters across a piece of tissue, but kill the tissue in the process, thus limiting temporal resolution. Integrated silicon biosensor arrays have been proposed as a method for detecting neurotransmitters in both the spatial and temporal domains. Using large arrays of microelectrodes placed at pitches comparable to the size of individual cells, a high resolution chemical image of neurotransmitters could be captured in real time. For such an array, a large number of electronic components are necessary. Two such components are high precision amplifiers and analog-to-digital converters which are necessary to amplify the extremely small chemical signals and then convert them to digital values such that they can be stored and analyzed. These components must be low power to avoid generating heat, and small in size in order to limit total silicon area. This thesis proposes the design of a low power switched-capacitor amplifier and Sigma-Delta modulator for use as an analog-to-digital converter. The switched-capacitor amplifier achieves a gain of 40dB with -63.7dB total harmonic distortion while using 6.82μW and occupying 0.076mm2 silicon area. The Sigma-Delta modulator achieves a signal-to-noise ratio of 86.8dB over 2kHz signal bandwidth and uses 9.1μW while occupying 0.043mm2 silicon area. Both of these designs were implemented in a 0.18μm CMOS process with a supply voltage of 900mV and their functionality verified was in silicon.Item Open Access Rapid early design space exploration using legacy design data, technology scaling trend and in-situ macro models(Colorado State University. Libraries, 2009) Thangaraj, Charles V. K., author; Chen, Tom, advisorCMOS technology scaling trend, i.e. the doubling of the operating frequency and the doubling of the number of transistors on a die every eighteen months, also know as Moore's Law has been a fundamental driver for the semiconductor industry for well over three decades. Scaling CMOS technologies into deep sub micron especially into sub 100 nm dimensions have caused a significant shift in business and design philosophy, and methodology. In addition to the semiconductor industry maturation there are seven key disruptive trends impacting the semiconductor industry. They are competitive landscape changes, technology convergence, greater global connectedness, increased design complexity, commoditization, consumerization, and the soaring research, development and engineering costs. These disruptions have made traditional business models increasingly ineffective and the benefits of Moore's Law insufficient for sustained competitiveness [1]. 'More-than-Moore' approach to heterogeneous system integration and holistic system optimization strategies in addition to the benefits of technology scaling are necessary for future success [2] [3].