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Browsing by Author "Chen, Thomas W., advisor"

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    A microphysiological system for studying barrier health of live tissues in real time
    (Colorado State University. Libraries, 2024) Way, Ryan, author; Chen, Thomas W., advisor; Wilson, Jesse, committee member; Chicco, Adam, committee member
    Epithelial cells create barriers that protect many different components in the body from their external environment. The gut in particular carries bacteria and other infectious agents. A healthy gut epithelial barrier prevents unwanted substances from accessing the underlying lamina propria while maintaining the ability to digest and absorb nutrients. Increased gut barrier permeability, better known as leaky gut, has been linked to several chronic inflammatory diseases. Yet understanding the cause of leaky gut and developing effective interventions are still elusive due to the lack of tools to maintain tissue's physiological environment while elucidating cellular functions under various stimuli ex vivo. This thesis presents a microphysiological system capable of recording real-time barrier permeability of mouse gut tissues in a realistic physiological environment over extended durations. Key components of the microphysiological system include a microfluidic chamber designed to hold the live tissue explant and create a sufficient microphysiological environment to maintain tissue viability; proper media composition that preserves a microbiome and creates necessary oxygen gradients across the barrier; integrated sensor electrodes and supporting electronics for acquiring and calculating transepithelial electrical resistance (TEER); and a scalable system architecture to allow multiple chambers running in parallel for increased throughput. The experimental results demonstrate that the system can maintain tissue viability for up to 72 hours. The results also show that the custom-built and integrated TEER sensors are sufficiently sensitive to distinguish differing levels of barrier permeability when treated with collagenase and low pH media compared to control. Permeability variations in tissue explants from different positions in the intestinal tract were also investigated using TEER revealing their disparities in permeability. Finally, the results also quantitatively determine the effect of the muscle layer on total epithelial resistance.
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    Automated sample preparation using adaptive digital microfluidics for lab-on-chip devices
    (Colorado State University. Libraries, 2018) Grant, Nicholas, author; Chen, Thomas W., advisor; Chong, Edwin, committee member; Geiss, Brian, committee member
    There have been many technological advances in the medical industry over the years giving doctors and researchers more information than ever before. Technology has allowed more sensitive and accurate sensors and has also driven the size of many sensor devices smaller while increasing sensitivity. However, while many aspects of technology have seen improvements, the sample preparation of biological tests has seen lagging development. The sample preparation stage is defined here as the extracting of required features from a given sample for the purpose of measurement. A simple example of this is the solid phase extraction of DNA from a blood sample to detect blood borne pathogens. While this process is common in laboratories, and has even been automated by large and expensive equipment, it is a difficult process to mimic in lab-on-chip (LoC) devices. Nucleic Acid isolation requires common bench top equipment such as pipettes, vortexers, and centrifuges. Current lab based methods also use relatively large amounts of reagents to perform the extraction adding to the cost of each test. There has been a lot of research improving sensing techniques proposed for Lab on Chip devices, but many sensing methods still require a sample preparation stage to extract desired features. Without a complimentary LoC sample preparation system, the diversity of LoC device remains limited. The results presented in this thesis demonstrate the general principle of digital microfluidic device and the use of such device in a small hand-held platform capable of performing many sample preparation tasks automatically, such as the extraction and isolation of DNA. Liquids are transported using a technique called Eletro-wetting on Dielectric (EWOD) and controlled via a programmable microprocessor. The programmable nature of the device allows it to be configured for a variety of tests for different industries. The device also requires a fraction of the liquids lab based methods use, which greatly reduces the cost per test. The results of this thesis show a promising step forward to more capable LoC devices.
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    Design methodology and productivity improvement in high speed VLSI circuits
    (Colorado State University. Libraries, 2017) Hossain, KM Mozammel, author; Chen, Thomas W., advisor; Malaiya, Yashwant, committee member; Pasricha, Sudeep, committee member; Pezeshki, Ali, committee member
    To view the abstract, please see the full text of the document.
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    Design of integrated on-chip impedance sensors
    (Colorado State University. Libraries, 2014) Kern, Tucker, author; Chen, Thomas W., advisor; Pezeshki, Ali, committee member; Tobet, Stuart, committee member
    In this thesis two integrated sensor systems for measuring the impedance of a device under test (DUT) are presented. Both sensors have potential applications in label-free affinity biosensors for biological and bio-medical analysis. The first sensor is a purely capacitive sensor that operates on the theory of capacitive division. Test capacitance is placed within a capacitive divider and produces an output voltage proportional to its value. This voltage is then converted to a timedomain signal for easy readout. The prototype capacitive sensor shows a resolution of 5 fF on a base of 500 fF, which corresponds to a 1 % resolution. The second sensor, a general purpose impedance sensor calculates the ratio between a DUT and reference impedance when stimulated by a sinusoidal signal. Computation of DUT magnitude and phase is accomplished in silicon via mixed-signal division and a phase module. An automatic gain controller (AGC) allows the sensor to measure impedance from 30 Ω to 2.5 MΩ with no more than 10 % error and a resolution of at least .44 %. Prototypes of both sensing topologies were implemented in a .18 μm CMOS process and their operation in silicon was verified. The prototype capacitive sensor required a circuit area of .014 mm2 and successfully demonstrated a resolution of 5 fF in silicon. A prototype impedance sensor without the phase module or AGC was implemented with a circuit area of .17 mm2. Functional verification of the peak capture systems and mixed-signal divider was accomplished. The complete implementation of the impedance sensor, with phase module and AGC, requires an estimated .28 mm2 of circuit area.
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    Design, fabrication and testing of an electrically controlled microfluidic capillary microvalve based on hydrophobicity
    (Colorado State University. Libraries, 2019) Kulkarni, Gitesh S., author; Chen, Thomas W., advisor; Chong, Edwin K. P., committee member; Geiss, Brian, committee member
    Microfluidics is a promising disciple that combines "micro" amount of fluid handling in "micro" sized channels and has found applications in diverse fields such as biotechnology and environmental monitoring. Combination of microfluidics with digital electronics technology has spurred creation of Lab-on-a-Chip (LOC) devices that are field-deployable and bought to market in the last few decades. In these devices, positioning/transportation of liquids has remained a critical issue. A sample of fluid needs to be acquired from a specimen reservoir and moved to a different reservoir location for analysis. Inexpensive, reliable and straightforward methods to do this transportation makes such instruments low-cost and robust for use in the field for a variety of purposes. Current ways to do fluid movement require high electric field and hence requiring the use of high voltages (thousands of volts), making the device bulkier. Another approach to use a pneumatic pump for droplet movement is also detrimental in making LoC devices portable due to sizes of associated electronics and electrical parts. This thesis presents the design of a microfluidic valve using capillary action, hydrophobicity, and low voltages (several volts). The use of low voltages brings the "micro" realm to the digital electronics part of LOC. It could lead to better portability, low-power operation of LOC devices, and consequently more adoption in field applications. The design process is based on practical considerations found during experimentation. This method was tested, and results are presented for various biochemical mediums, including KCl, PBS, GMOPS, Cell culture and FBS.
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    Study of real-time spatial and temporal behavior of bacterial biofilms using 2D impedance spectroscopy
    (Colorado State University. Libraries, 2019) Begly, Caleb R., author; Chen, Thomas W., advisor; Wilson, Jesse, committee member; Chicco, Adam, committee member
    The study of biofilms and their effect on disease treatment, prevention, and cures has been increasing in importance in recent years. Bacterial biofilms are colony formations developed by bacteria that allow them to anchor onto a surface and survive hostile environments. The formation of harmful bacteria biofilms on some surfaces can be troublesome, particularly in the case of medical implants. The continuing rise of antibiotic-resistant bacteria over the past decade had escalated the need to study and understand biofilms. This thesis presents the design of a multi-channel impedance spectroscopy instrument to allow 2D spatial and temporal evaluation of biofilm growth. The custom-designed circuits allow measurement updates once per second on the entire set of impedance sensors. The distance between the neighboring sensors is 220 micrometers, allowing realtime observation of biofilm growth. The initial results show that the proposed 2D impedance spectroscopy tool provides the needed accuracy to predict the existence of bacteria biofilm at a given sensor location. The initial results were validated using optical images with fluorescent staining.