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Individual Fellowships H2020-MSCA-IF-2017

 

PREMOTHER Project

 

PREvention of MOther-to-child Transmission of HIV and Syphilis using an Electrochemical Readout based on DNA Switches

ABSTRACT

There remains a pressing need for point-of-care antibody detection that is both analytically precise (improving clinical specificity) and easily multiplexed (improving clinical sensitivity). In particular, existing point-of-care methods for the detection of specific, disease-diagnostic antibodies (e.g., lateral flow immunoassay) are qualitative, which reduces clinical specificity (due to the subjective nature of their visual readout), and are difficult to multiplex, reducing their clinical sensitivity (because they fail in patients that don’t seroconvert against the single antigen the device presents). Laboratory-bound techniques (e.g., ELISAs, immunoprecipitation, immunocytochemistry), in contrast, overcome both of these limitations, but are expensive, overhead intensive, and slow, generally requiring a day or more to return an answer to the clinician. Given the above, a technology that combines the best attributes of both point-of-care and laboratory techniques would thus significantly enhance our ability to detect, monitor and treat diseases. Here I propose the development of just such a technology. Specifically, I propose to develop a platform that supports the rapid, low-cost, quantitative measurement of multiple, specific antibodies (diagnostic of infections, autoimmune disease, immunization status) in minutes using just a single finger-prick blood sample (Figure 1). As a test bed for the development of this platform, I will focus on the detection of multiple diagnostic antibodies of HIV and syphilis. Nowadays, the mother-to-child transmission of HIV and syphilis causes approximately 305,000 fetal and neonatal deaths every year and leaves 215,000 infants at increased risk of dying from prematurity, low-birth-weight or congenital disease. An accurate diagnosis of diagnostic-antibodies and antiretroviral therapy could stop all those deaths.

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OBJECTIVE

The goal of PREMOTHER is the development of a rapid (<10 min), convenient (single-step), low-cost (<2 EUR/test) method for the quantitative measurement of multiple (~8) antibodies in a finger-prick blood sample at point-of-care.

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This implies:

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1. The design, optimization and laboratory-scale testing of DNA switch electrochemical sensors for the detection of HIV and syphilis diagnostic antibodies in blood.

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2. The integration of validated DNA switches into a multiplexed electrochemical device suitable for point-of-care.

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3. The optimization of the full-up platform to achieve clinically relevant sensitivity and specificity, as well as sufficient ease-of-use, robustness and speed to support point-of-care use.

- Host Institution: Catalan Institute of Nanoscience and Nanotechnology

Supervisor: Prof. Arben Merkoçi, PhD

- Collaborators: Prof. Kevin W. Plaxco 

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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant agreement No 795635.

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