Overdose Indicators - C&EN Global Enterprise (ACS Publications)

Aug 11, 2014 - ... they want to verify the diagnosis quickly before liver damage sets in. But that's not always possible. Now researchers report a gro...
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DIAGNOSTICS ON LINE TWO INSTRUMENTS: Affordable electrochemical device uses any cell phone to transmit data mobile electrochemical detector called uMED can test for a variety of molecular-level health or environmental indicators and then use any cell phone on any cellular network to transmit results for remote analysis and diagnosis. The device, which costs about $25, could give people in resource-limited areas the ability to perform tests typically carried out by expensive laboratory electrochemical instruments. Developed by George M. Whitesides of Harvard University and coworkers, uMED is based on a simple blood glucose monitor (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/ pnas.1405679111). The device mixes samples by vibration and uses test strips or electrodes together with a potentiostat to analyze them by any of several electrochemical methods: chronoamperometry, cyclic voltammetry, dif-

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ALEX NEMIROSKI

Electrochemical detector (right) uses the voice channel of a cell phone to transmit data for analysis.

OVERDOSE INDICATORS BIOMARKERS: MicroRNAs may pick

up acetaminophen poisoning

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Acetaminophen

“Often the people who come in are in a state where they can’t report what’s happened to them.”

HEN DOCTORS in the emergency room

suspect that a patient has overdosed on the popular painkiller acetaminophen, they want to verify the diagnosis quickly before liver damage sets in. But that’s not always possible. Now researchers report a group of 11 biomarkers that, if validated in large groups of patients, might be a rapidly detectable signature of acetaminophen poisoning and a sensitive indicator that emergency treatment is working (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/ pnas.1412608111). Some 78,000 Americans show up at hospitals because of acetaminophen overdoses each year. “Often the people who come in are in a state where they can’t report what’s happened to them,” explains Victor R. Ambros, who led the new work. When administered soon after an overdose, N-acetylcysteine can mitigate liver damage. But the traditional biomarker, the enzyme alanine aminotransferase, can take 72 hours to peak in the bloodstream and is not CEN.ACS.ORG

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ferential pulse voltammetry, square wave voltammetry, or potentiometry. Using a cell phone’s headphone jack and voice channel, uMED uploads sample data to a data management network. This voice-based data transfer approach ensures that the device is compatible with any mobile phone and with cellular networks from 2G to 4G. The network records and analyzes the data, and results and advice are returned to the user via text message to the same phone. The researchers note that in most cases previous mobile reporting and point-of-care diagnostic systems required users to enter data by hand, were more limited functionally and lacked network connectivity, or required sophisticated equipment and technologies available primarily in developed countries. The team demonstrated uMED by using it to detect trace amounts of toxic heavy metals in drinking water, measure glucose in blood, monitor sodium in urine, and perform an electrochemical enzyme-linked immunosorbent assay for malaria antigen. The study implements “a couple of clever ideas, including the vibration mechanism for on-board sample mixing and the audio jack as a universal communication mechanism,” comments biomedical engineer Samuel K. Sia of Columbia University. “Further work would involve deploying the device in a field setting to gather data and user feedback.”—STU BORMAN

specific to acetaminophen poisoning. So physicians approached Ambros, a biologist at the University of Massachusetts Medical School, and asked him to look into microRNAs as acetaminophen poisoning indicators. MicroRNAs—short RNA strands that regulate gene expression—are promising biomarkers for many diseases, says James Dear, an expert on acetaminophen poisoning at Scotland’s University of Edinburgh who wasn’t involved with the work. Prior work showed that microRNAs can detect liver toxicity earlier than other biomarkers, he points out. This turns out to be true for acetaminophen poisoning as well. Ambros’s team analyzed blood samples from 49 patients and found 11 microRNAs that spiked in concentration more rapidly than alanine aminotransferase during acetaminophen overdose. They also decreased more quickly in response to treatment. Ambros will study more patients to confirm the results. The 11 microRNAs occur at attomolar levels in the bloodstream and during poisoning can increase anywhere from 10- to 100-fold. Ambros’s team used quantitative real-time polymerase chain reaction to detect those changes. Although finding the biomarkers is an achievement, “the technique itself is a little brute force” for emergency room blood work, says Robert M. Corn, who develops microRNA profiling tools at the University of California, Irvine. Ambros agrees, saying, “We’re working on adapting assays to more straightforward platforms.”—CARMEN DRAHL

AUGUST 11, 2014