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Translational Lab-on-a-Chips with the Development of a Novel Cancer Screening Method

Browne, Andrew W.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275659036

Abstract Details

2010, PhD, University of Cincinnati, Engineering : Electrical Engineering.
In this research, trans-disciplinary advances are made in the fields of microfluidics, point of care testing (POCT) and cancer screening. A tumor-bearing subject is injected with a cancer-targeting gene delivery vector that selectively induces production of a secretable serum biomarker from tumor tissue and not healthy tissue is coupled with biomedical microfluidic devices which sample blood from the subject and perform analysis on the blood for presence of the serum. The unifying goal of these technologies is the detection of cancer by identifying an exogenously induced serum biomarker in subjects in a tumor-dependent manner. First, methods for rapidly fabricating microfluidic devices are developed so that the devices used as part of the cancer screening method can be designed and optimized in an iterative fashion. Second, flow control in microfluidic devices is achieved using a new design for a modular pinch valve for incorporation into microfluidic devices produced in rigid polymer substrates. Then a microfluidic device for intermittent blood sampling from catheterized patients is designed, produced and characterized for fluid control, sample collection and cross-contamination. Next a, a microfluidic blood analysis chip is designed to incorporate three functions: serum separation, hematocrit evaluation and serum biomarker quantitation. The devices function is characterized for serum separation on small blood samples (<1.5 µL), evaluation of hematocrit using a novel gray scale image analysis approach and detection of serum biomarker down to 10 ng/mL. Finally, a novel cancer screening method is developed whereby an oncolytic Herpes Simplex Virus is engineered to deliver a genetic payload which induces secretable biomarker expression in a tumor selective manner. The novel HSV mutant is characterized in vitro and in vivo for several tumor models in different anatomical locations. Specific tumor models are identified as highly susceptible to this screening approach as seen in extremely high biomarker induction while other tumor models with lower biomarker expression are still identifiable by this screening approach.
Chong Ahn, PhD (Committee Chair)
Jason Heikenfeld, PhD (Committee Member)
Ian Papautsky, PhD (Committee Member)
John Bissler, MD (Committee Member)
Tim Cripe, MD, PhD (Committee Member)
185 p.
Biomedical Research
Lab-on-a-Chip; micro total analysis; cancer screening; herpes simplex virus; microfabrication; blood analysis

Recommended Citations

Citations

  • Browne, A. W. (2010). Translational Lab-on-a-Chips with the Development of a Novel Cancer Screening Method [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275659036

    APA Style (7th edition)

  • Browne, Andrew. Translational Lab-on-a-Chips with the Development of a Novel Cancer Screening Method. 2010. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275659036.

    MLA Style (8th edition)

  • Browne, Andrew. "Translational Lab-on-a-Chips with the Development of a Novel Cancer Screening Method." Doctoral dissertation, University of Cincinnati, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275659036

    Chicago Manual of Style (17th edition)

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© 2010, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.