Stamp-Sized Device Could Cut Liver Test Costs

By Michael Smith, North American Correspondent, MedPage Today

Published: September 20, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

A paper-based device about the size of a postage stamp could improve testing for drug-induced liver toxicity in the developing world, researchers reported.

In a series of experiments, the device agreed more than 90% of the time with the gold-standard tests for liver enzymes, according to Nira Pollock, MD, PhD, of Beth Israel Deaconess Medical Center in Boston, and colleagues.

At a projected cost of less than 10 cents a test, the device could make it significantly easier to monitor patients being treated for such diseases as TB and HIV in the developing world, where standard testing is difficult to obtain and costly, Pollock and colleagues reported in the Sept. 19 issue of Science Translational Medicine.

"Our device is designed to use a droplet of blood from a finger prick to deliver results in 15 minutes," Pollock said in a statement. "It could have significant implications around the world, particularly in developing nations where blood tests can be prohibitively expensive and the results can sometimes take weeks to return."

The device uses layers of patterned paper and a plasma separation membrane. Blood applied to the plasma separation membrane wicks into the layers of paper and travels through microfluidic channels to separate zones for testing aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

The read-out is a series of dots that change color to report levels of the enzymes in three "bins" – less than 3 times the upper limit of normal (ULN), 3 to 5 times ULN, and more than 5 times ULN – that correspond to cut-offs used for clinical management of patients with TB and HIV, Pollock and colleagues reported.

The device was developed in collaboration with Diagnostics For All, a Cambridge, Mass., nonprofit organization.

The researchers tested the device on paired whole-blood and serum specimens, drawn simultaneously from 223 patients within the previous 5 hours for routine clinical testing and for which results of standard automated transaminase testing were available.

They applied 30 microliters of blood or serum to the devices and – after 15 minutes – three readers blinded to the gold-standard outcomes analyzed the results.

ALT results were more accurate for the serum samples than for whole blood, the researchers noted, possibly because of the age of the specimens at the time of analysis. Previous experiments had shown that values drifted higher as the whole blood aged.

But overall, Pollock and colleagues reported, the paper device got it right at least 90% of the time and was especially accurate in placing specimens in the lowest bins – those that would usually mean no action was needed.

For example, the paper device correctly placed 88 of 89 serum samples tested for ALT in the less than 3 times ULN bin and 85 of 88 tested for AST – accuracies of 99% and 97%, respectively.

No specimens that the standard test placed above 5 times ULN were misread by the paper device to be below 3 times ULN, Pollock and colleagues reported – an important finding given that guidelines for TB treatment suggest that patients with levels more than 5 times ULN stop their medications even in the absence of symptoms.

Pollock and colleagues cautioned that the device has still to be tested in the field with TB and HIV patients. A planned field trial in Ho Chi Minh City, Vietnam, will evaluate the performance of the test in 600 HIV patients from that city's Hospital of Tropical Diseases.

The study had support from the Department of Defense/Center for Integration of Medicine and Innovative Technology, the National Institutes of Health, and the Bill & Melinda Gates Foundation. A patent application has been filed based on the results; four authors are listed as inventors.

Primary source: Science Translational Medicine
Source reference:
Pollock NR, et al "A paper-based multiplexed transaminase test for low-cost, point-of-care liver function testing" Sci Transl Med 2012; DOI: 10.1126/scitranslmed.3003981.

Source