It may be possible to develop blood tests for infectious diseases by screening random libraries of non-biological molecular shapes, according to recently published data from the University of Pittsburgh. 

“This ‘needle-in-a-molecular haystack’ approach is a new way to develop diagnostic assays,” senior author Donald S. Burke, MD,Pitt Graduate School of Public Health dean and director of Pitt’s Center for Vaccine Research said in a prepared statement about the study. “The method does not rely on starting with known viral components. This is important because there are conditions for which there isn’t a known antigen, such as newly emerged epidemics, autoimmune diseases or even responses to traumatic injury.”

  
The Pitt researchers used a technique that synthesizes random molecular shapes called “peptoids” hooked onto microscopic plastic beads. The technique can produce millions of molecular shapes. The peptoids are not organic, but if they match to the corresponding shape on an antibody, that antibody will connect to them, allowing the scientist to pull out that bead and examine that peptoid and its corresponding antibody.
 
Using this technique, Dr Burke’s team chemically generated a huge library of random molecular shapes. Then, using blood from patients with HIV and from people who did not have HIV, the researchers screened a million of these random molecular shapes to find the ones that bound only to antibodies present in the blood of HIV-infected patients, but not the healthy controls. No HIV proteins or structures were used to construct or select the peptoids, but the approach, nonetheless, successfully led to selection of the best molecular shapes to use in screening for HIV antibodies.

The team then resynthesized that HIV-antibody-targeting peptoid in mass and tested it by screening hundreds of samples from the Multicenter AIDS Cohort Study (MACS), which supported by the National Institutes of Health


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Study researchers selected the samples, but blinded the testers to which samples were HIV-positive or -negative.  The test distinguished between the samples of HIV-positive blood and HIV-negative blood with a high degree of accuracy.

The study was funded by the Bill & Melinda Gates Foundation.

Reference

1. Gearhart TL, Montelaro RC, Schurdak ME, et al. Selection of a potential diagnostic biomarker for HIV infection from a random library of non-biological synthetic peptoid oligomers. J Immunological Method.  2016; DOI: 10.1016/j.jim.2016.05.001