New Technique Rapidly Detects Needle-in-a-Haystack Plasma Biomarkers for Disease Diagnosis

Blood plasma, routinely collected during medical care and research, has the potential to be an abundant source of protein biomarkers. These markers can serve diagnostic and prognostic roles, measure treatment response, and provide insights into disease biology. However, finding such biomarkers in plasma using proteomics, the most advanced tool currently available, is challenging. This is because 99% of plasma is composed of common proteins like albumin, globulins, and coagulants that essentially hide potential biomarkers. These same proteins are repeatedly identified in a plasma sample, making the detection of the less abundant but interesting proteins difficult. While scientists have attempted to remove these common proteins from plasma samples using antibodies, the process has been found to be costly, time-consuming, and not robust enough for large-scale usage. Now, a team of researchers has developed a new, rapid, and cost-effective method to remove these proteins by repurposing an old biochemical technique from 1948.

Researchers at Boston Children's Hospital (Boston, MA, USA) came upon a technique previously mentioned in literature on protein and peptide studies that could be applied to plasma. During the COVID-19 pandemic, the researchers were tasked with analyzing the proteins in 5,000 plasma samples for a study looking at immune responses in about 1,100 hospitalized COVID-19 patients. This task had to be accomplished at a time when many labs were closed due to the pandemic. In a span of three months, the researchers had to develop a method to analyze ten times the amount of plasma samples than they typically handled daily. The team successfully accomplished this task, and their work contributed to the identification of tissue- and organ-specific biomarkers, which accurately predicted the progression of hospitalized COVID-19 patients.

This new technique employs perchloric acid, a very potent superacid, along with very low temperatures (-20°C) to separate the common proteins within as little as 15 minutes, without harming the remaining proteins. The unwanted proteins coagulate similar to how milk curdles in lemon juice. The samples can then be centrifuged, and the liquid at the top, which contains the required proteins, can be collected. This method is fast enough for large-scale use, depleting the unwanted proteins at a cost of only USD 2.50 per sample, significantly lower than current costs. This technique enables the detection of over 1,500 proteins per sample at a rate of 60 samples per day.

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