Low-Resource Diagnostics
Delivery of diagnostic tools to low resource settings faces numerous challenges in areas where it is difficult to reach populations that are distributed sparsely over rural areas. Health workers dispatched from centralized facilities face difficult terrain, intermittent/lack of electricity, poorly equipped facilities, unskilled workforce, and limited financial resources. The consequences of these limitations are that diagnostic medical technologies common in industrialized regions are either not usable or affordable. With funding from the Bill and Melinda Gates Foundations, we are exploring interesting methods for the creation of low-resource diagnostic tools. This area of research in the lab is broken down into several projects:
1) Low-resource extraction and processing of biological samples
This Bill & Melinda Gates Foundation funded project (in collaboration with Dr. Rick Haselton of Vanderbilt's Department of Biomedical Engineering) is a sample collection, concentration and preparation component for integration with downstream detection components to form a general diagnostic platform suitable for low resource environments. This self-contained processing device captures targets of interest from complex biological matrices on the surface of a carrier bead. The biomarker-bound magnetic beads are then entrained by an external magnetic field and transported through each of the three wash solutions. Processing removes sample interferents, and the biomarker target is concentrated in the final chamber for subsequent analysis. The device has advantages over existing extraction technologies, mainly it that it can be implemented to: (1) require little or no power, (2) be suitable for an unskilled user, (3) have rapid time-to-extraction, (4) be low cost, and (5) be adaptable to multiple downstream detection designs. The modularity of this device toward targeting various biomarker targets is evidenced by the creation of several devices for the extraction of: (1) proteins (malaria), (2) nucleic acids (RSV, TB), and (3) whole cells (HIV) from a host of biological matrices (blood, plasma, saliva, urine, cells)
Graduate Students/Post-Docs on this project:
Dr. Joseph Conrad (HIV)
Nick Adams (RSV)
Keersten Davis (Malaria-blood)
Anna Bitting (Malaria-saliva)
2) Coffee Ring Diagnostics for Malaria
We have developed an antibody-free, malarial assay based on the phenomenon that forms coffee ring stains on a kitchen counter. The unique microfluidics present in an evaporating drop of colloidal solution produce a characteristic “coffee ring” stain of small particles visible with the naked eye. In the presence of a droplet of sample containing the histidine-rich protein-II (HRP-II) of P. falciparum, a readily visible colorimetric ring is produced indicating malarial infection upon aggregation with Ni(II)NTA-functionalized gold nanoparticles. In addition to studying the formation of the coffee ring itself, we are also exploring how the surface chemistry of the glass slide affects the formation of the ring structure. By conjugating a glass slide with varying concentrations of Ni(II)NTA and backfill ligands, we can fine-tune the contact angle of the droplet, and thus attenuate the formaiton of the ring. This robust approach addresses many of the problems currently associated with low-resource malarial diagnostics.
Graduate Students/Post-Docs on this project:
Chris Gulka
Keersten Davis
In both of these projects, assay optimization is a big aspect of the developmental stage. See below figure for our thoughts on this:
