[CCoE Notice] Dissertation Announcement: Maede Chabi, "Fundamental Mechanisms of Membrane Immunoassays and Application to Rapid Cancer Diagnosis"

[Greenwell, Stephen J]

[Dissertation Defense Announcement at the Cullen College of Engineering]
Fundamental Mechanisms of Membrane Immunoassays and Application to Rapid Cancer Diagnosis
Maede Chabi
November 19, 2024 - 12 p.m. (CST)
Location: Agrawal Engineering Research Building (AERB), Room 222

Zoom:
https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/86104346054?pwd=e14rvwLLLYk6QzOhZRteieo1Pci110.1__;!!LkSTlj0I!B7lU5DsppwyRoieozU9y12ZKffy9glAU3omedRnQ1fhnoAtwYwpQgA0pcwszhEHArm85NUEAmWTdJN21YvnRkjCLiOw$ 

Meeting ID: 861 0434 6054
Passcode: 309525
Committee Chair:
Richard C. Willson, Ph.D. | Jacinta C. Conrad, Ph.D.
Committee Members:
Sergey Shevkoplyas, Ph.D. | Katerina Kourentzi, Ph.D. | Kirill Larin, Ph.D. | Ran An, Ph.D. | Rashmi Kanagal-Shamanna, M.D. | Binh Vu, Ph.D.
Abstract
Lateral flow assays are point-of-care analytical platforms that fulfill the demand for rapid, low-cost, and accessible testing platforms for many different applications including infection diagnostics. However, these platforms struggle with lower sensitivity compared to more elaborate diagnostic tests. We tackled this challenge by introducing a chemiluminescence-based lateral flow assay for highly sensitive detection of COVID-19 in nasal swab clinical matrices. We used HRP and antibody-coupled bacteriophage as LFA reporter particles and an ECL substrate for generating a chemiluminescence signal corresponding to HRP concentration. We were able to achieve a low limit of detection of 25 pg mL-1 SARS-CoV-2 nucleoprotein spike in a nasal swab extract matrix using a FluorChem system to detect the signals, and 100 pg mL-1 when integrated with a POC in-house-developed smartphone-based reader. Moreover, we demonstrated that the smartphone-based phage-LFA can statistically distinguish between the LFA signal from COVID-19 positive (N=15) and negative (N=11) nasal swab samples (p < 0.001). The proposed smartphone-readable phage-LFA technology allows rapid, affordable, and sensitive detection of COVID-19 and is translatable for other applications.
Despite cancer diagnosis typically not being considered urgent, acute promyelocytic leukemia is a type of cancer that requires urgent diagnosis because it can lead to death within a few days due to severe hemorrhagic complications. APL is highly treatable and its early detection can enable successful treatment and prevent early death. We responded to the current demand for timely diagnosis of rapidly fatal acute promyelocytic leukemia (APL) by introducing a sensitive time-resolved fluorescent-based LFA to detect the hallmark of APL, the PML-RAR* fusion protein, in cell lysate. Our LFA achieved sensitivity sufficient to meet the WHO guideline of detecting at least 20% blasts. We were able to detect at least 10% NB4 cells (promyelocytic blasts) in healthy PBMC and 20% in HL60 AML cell line background. We also showed the specificity of this LFA by comparing the signal from NB4 APL cell lysate to signals from multiple non-APL cell lines.
Finally, we introduced the use of rapid filtration to allow measurement of the adsorption of biomolecules in porous matrices on the short time scales associated with lateral flow assays and membrane chromatography, below one second. We studied the adsorption of fluor-dyed IgG molecules in solution to protein A immobilized on a porous membrane. We showed this technology can be utilized to assess the adsorption under various conditions at timescales not achievable by other methods.
[Engineered For What's Next]


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