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Development of a Wearable Noninvasive Biomarker Sensing Platform

Gupta, Niraj Kumar

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2017, Doctor of Philosophy, University of Toledo, Biomedical Engineering.
Biomarkers are any components in the human body in the form of biomolecules, cells, tissues, or fluids that can be measured and evaluated to facilitate the indication of healthy processes, pathological processes, or pharmacological responses to a therapeutic intervention. Numerous ongoing research investigations in the identification of such components have offered potential means of early disease prognosis and assessment of the impact of fatigue and/or stress on human physical and cognitive performance. Currently, studies on human performance biomarkers are some of the highly investigated areas in this field. These include, but are not limited to lactate, cortisol, and orexin A for the quantification of physical and cognitive state. It is preferred to monitor such biomarkers unobtrusively in real time which can impact a number of professions with high-risk tasks such as surgeons, anesthesiologists, commercial pilots, and combat forces. Especially, in the military services, a device with similar capability would greatly assist in their sense-assess-augment paradigm by monitoring the performance of a soldier in the field. For the implementation of such a system, one of the most challenging aspects is bio-sample collection. Traditionally, phlebotomy is used as the gold standard for sample collection. However, it is painful, inconvenient and unsuitable for the purpose described as it can significantly limit the sampling interval. Some other noninvasive alternatives like saliva and passive sweat may be considered as possible sources. Nevertheless, they carry some shortcomings like imprecision, requirement of volume normalization, and possible need of controlled supervision for the sample collection and analysis. A technique known as reverse iontophoresis can overcome some of these issues in addition to providing a more precise sampling. It facilitates transdermal extraction of charged and neutral biomolecules up to 20 kDa in size present in the interstitial fluid by passing a low-level current between two electrodes placed over the skin. The extracts on the skin surface can then be analyzed by an on-site biosensor, or transported to a dedicated analyzer via a microfluidic pathway. It should be noted, however, the concentrations of RI sampled analytes are at significantly lower levels compared to those found in blood samples. Therefore, highly sensitive biosensors are required for the quantification of these samples. One of the widely used sensing techniques that could be potentially integrated to develop a RI-based sensing platform would be the chronoamperometric method. However, this technique may not be suitable for some larger peptides and protein-based biomarkers such as cortisol, and orexin A that require highly sensitive biosensors and potentially demand the integration of a microfluidic interface for the RI-based sample to flow over the sensor surface. Although the technologies required to develop a noninvasive biomarker sensing platform for various types of analytes are available, there is still an unmet need of a robust platform that integrates them into a single wearable device. In this dissertation, this need has been addressed by successfully developing a RI-based sensing platform that integrates amperometric and SPR-based sensors along with the necessary electronics and microfluidic interfaces. To accomplish this, commercially available application specific integrated circuits were used to design the essential electronics for a miniature RI driver module, amperometric and SPR sensor interfaces, and a microfluidic flow controller. A microfluidic interface that houses a micro electro-osmotic pump and a disposable cartridge for the sample collection and transport to a SPR-based sensor was also developed. Furthermore, a planar electrode system and enzymatic hydrogels were fabricated for chronoamperometric sensing of glucose and lactate. Ultimately, these components were integrated into a single wearable prototype.
Brent Cameron, PhD (Advisor)
David Giovannucci, PhD (Committee Member)
Dong-Shik Kim, PhD (Committee Member)
Eda Yildirim-Ayan, PhD (Committee Member)
Stephen Callaway, PhD (Committee Member)
Casey Pirnstill, PhD (Committee Member)
Scott Pappada, PhD (Committee Member)
241 p.

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Citations

  • Gupta, N. K. (2017). Development of a Wearable Noninvasive Biomarker Sensing Platform [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513362181154842

    APA Style (7th edition)

  • Gupta, Niraj. Development of a Wearable Noninvasive Biomarker Sensing Platform. 2017. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513362181154842.

    MLA Style (8th edition)

  • Gupta, Niraj. "Development of a Wearable Noninvasive Biomarker Sensing Platform." Doctoral dissertation, University of Toledo, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1513362181154842

    Chicago Manual of Style (17th edition)