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Glasgow Team Devises Sensor for POC Metabolite Assays

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NEW YORK (360Dx) – Researchers at the University of Glasgow have developed a handheld complementary metal oxide semiconductor-based (CMOS) device for multiplexed measurement of disease-linked metabolites.

Described in a paper published last month in Biosensors and Bioelectronics, the technology could prove useful for inexpensive point-of-care testing of a variety of analytes, said Samadhan Patil, a Glasgow researcher and first author on the study.

The device uses established enzymatic assays for target metabolites. In such assays, an enzyme specific to a particular metabolite substrate is introduced to a sample and the metabolite is quantified based on the enzyme's rate of activity. These reactions take place in microwells fabricated on the surface of a CMOS chip.

The reaction produces an optical signal that can be detected by an array of photodiode sensors built into the chip. In the Biosensors and Bioelectronics study, the researchers integrated the chip with an Android-based app for acquiring, displaying, and storing the data.

They used the device to quantify the levels of four metabolites — choline, xanthine, sarcosine, and cholesterol — in human blood or urine. They then developed a separate assay for glucose and compared the results of their glucose and cholesterol tests to measurements generated on an Abbott Architect analyzer, finding no statistically significant difference between the two sets of results.

Having validated the performance of the device, they then multiplexed the initial set of four metabolites by dividing the CMOS chip into four separate microwells, one for each reaction. With this version of the device, they quantified levels of the four metabolites simultaneously, obtaining results in around two minutes.

Patil suggested the device could prove useful for in-home patient monitoring or for rapid testing in settings like ambulances or emergency departments.

He noted that similar devices currently exist — Abbott's i-Stat point-of-care system, for instance — but that these are not necessarily simple enough for patients to use themselves.

That said, the device as presented in the recent study is more a proof of concept than a finished product. One of the next areas of focus for the Glasgow team will be streamlining the sample preparation process, Patil said.

Currently, sample preparation and handling is done manually, with the researchers pipetting samples and reagents into the device's microwells. Patil said the researchers are currently developing another version of the device that uses a capillary flow-based system for the sample and liquid handling.

The authors noted that they "expect future versions of the technology to embed microfluidic sample handling and enzyme immobilization to remove the need for off-chip sample preparation."

In addition to eliminating the assay's manual sample prep and liquid handling components, the researchers are working to expand its multiplexing capabilities, Patil said, noting that the challenge is dividing the sensor arrays integrated into the chip into as many discrete microwell reaction chambers as possible without creating cross contamination between the chambers.

"We divide the chip into different sectors, and one sector, or microwell, is used for one metabolite," he said. "So the limit is our ability to make microchambers on top of the chip."

Patil said he believed the 16-by-16 array of sensor pixels used in the device could ultimately allow for multiplexing of around 25 different reactions and that in the near term he and his colleagues aimed to expand it to run 16 assays simultaneously. He added that the device could run essentially any enzyme-based metabolite assays, with costs running around $2 to $3 per test.

Patil said he and his colleagues are in discussions with a pair of companies about commercializing the device — one he described as a large IVD company and the other a smaller firm. He added that they anticipated a commercial version of the device could be available in three to five years.