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A Mobile Healthcare (mHEALTH) System Using Polymer Lab-On-A-Chip With Chemiluminescence Based High-Sensitive Immunoassay For Clinical Diagnostics

Ghosh, Sthitodhi
http://orcid.org/0000-0003-3456-2231
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1592170905649462

Abstract Details

2020, PhD, University of Cincinnati, Engineering and Applied Science: Electrical Engineering.
The objective of this research work is to develop a functional lab-on-chip (LOC) and a smartphone compatible point-of-care-testing (POCT) platform to quantitatively determine the concentration of a target biomarker in biological fluids for disease diagnostics in resource-limited environment. Majority of deaths related to infectious diseases occur in resource-poor countries having limited access to clinical laboratory facilities and trained personnel. Developing reliable diagnostic tests to be used at the point-of-care can result in earlier disease diagnosis, improved patient treatment, and more efficient outbreak prevention. The realization of an ideal POCT system largely relies on the development of cheap and disposable micro?uidic devices that can be easily integrated to low power electronics with a user-friendly interface.In this research, for the first time, a new microchannel capillary flow assay (MCFA) LOC for high-sensitive chemiluminescence ELISA using on-chip reagent lyophilization has been developed and applied for the detection of malarial biomarker Plasmodium Falciparum Histidine Rich Protein 2 (PfHRP2). This work also reports the design and development of a smartphone based POCT analyzer for detecting chemiluminescent signals from preloaded MCFA LOC. MCFA LOCs were designed for single-step sample loading and capillary liquid transport to initiate chemiluminescence sandwich ELISA in the reaction chambers. A methodology towards lyophilization of chemiluminescent substrate while restoring the substrate functionality in artificial serum was successfully established which paves the way towards developing a sample-to-answer type POCT platform . On sample addition, the functionally designed microchannels with adequately hydrophilic surfaces pull the sample towards the dried reagents and reconstitutes them.The designed microfluidic chip controls sequential arrival of reconstituted reagents in the reaction chamber producing the desired chemiluminescent light which can be correlated to the target biomarker concentration. No requirement of any external flow control and chemiluminescence based detection (which does not require any excitation source) makes the lab chip easily integrable to a smartphone through an attachable/detachable optical analyzer. A smartphone-based portable POCT analyzer was designed, developed and characterized for chemiluminescent detection from the preloaded MCFA LOC. The smartphone based portable analyzer system consists of an android smartphone , a low-level light detection circuit assembled in a 3D printed black box, and the fabricated MCFA LOC. The optical detector detects the chemiluminescence in the spiral reaction chambers of the MCFA chip, amplifies the signal and transmits digital data to the smartphone for processing and display. The smartphone powers the electronic circuit and communicates with it via an USB cable using the USB-OTG protocol. The overall functionality of the integrated system was validated with PfHRP2-spiked serum with results obtained within 20 minutes of sample addition. The standard curve calculated from the smartphone analyzer was comparable to conventional readers with clinically relevant limit of detection. This work thus reports the successful development of a hand-held POCT analyzer for detecting infectious diseases like malaria. The developed MCFA lab chip with the smartphone analyzer can be easily customized and can provide a low cost, low power, portable platform for fast and sensitive detection of various biomarkers for disease diagnostics and prevention.
Chong Ahn, Ph.D. (Committee Chair)
Marc Cahay, Ph.D. (Committee Member)
Leyla Esfandiari, Ph.D. (Committee Member)
Jungyoup Han, Ph.D. PMP (Committee Member)
Rashmi Jha, Ph.D. (Committee Member)
247 p.
Electrical Engineering
Capillary Microfluidics; Point of care Testing POCT; Lyophilization; Chemiluminescence Immunoassay; Infectious Disease; Mobile Healthcare

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Citations

  • Ghosh, S. (2020). A Mobile Healthcare (mHEALTH) System Using Polymer Lab-On-A-Chip With Chemiluminescence Based High-Sensitive Immunoassay For Clinical Diagnostics [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1592170905649462

    APA Style (7th edition)

  • Ghosh, Sthitodhi. A Mobile Healthcare (mHEALTH) System Using Polymer Lab-On-A-Chip With Chemiluminescence Based High-Sensitive Immunoassay For Clinical Diagnostics . 2020. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1592170905649462.

    MLA Style (8th edition)

  • Ghosh, Sthitodhi. "A Mobile Healthcare (mHEALTH) System Using Polymer Lab-On-A-Chip With Chemiluminescence Based High-Sensitive Immunoassay For Clinical Diagnostics ." Doctoral dissertation, University of Cincinnati, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1592170905649462

    Chicago Manual of Style (17th edition)

ucin1592170905649462
177
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This open access ETD is published by University of Cincinnati and OhioLINK.