A digital camera or smartphone visualizes bioluminescent characteristics of test sample to display levels of Phe in blood, potentially giving medical laboratories a way to support home-based or point of care metabolite tests

Clinical laboratories may soon have a new paper-based finger prick assay that can quickly measure metabolites in blood samples and enable patients who need to monitor certain conditions, such as congenital phenylketonuria, to do so at home.

The test also could be used at the point of care and in remote regions where larger, medical laboratory technology for monitoring metabolites in blood is limited.

Scientists at Max Planck Institute for Medical Research (MPIMR) in Heidelberg, Germany, and the Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland, have developed a molecular biosensor that measures quantities of certain metabolites in small blood samples, according to a news release. This biosensor is at the heart of the new paper-based assay.

They published their research in Science, a journal of the American Association For the Advancement of Science.

Molecular Biosensor Measures Multiple Metabolites in Blood

“We introduce a fundamentally new mechanism to measure metabolites for blood analysis. Instead of miniaturizing available technology for point-of-care applications, we developed a new molecular tool,” said Qiuliyang Yu, PhD, first author of the paper and scientist at the Department of Chemical Biology at the Max Planck Institute in Heidelberg, in the news release.

In their study, the scientists primarily measured concentration of phenylalanine (Phe) in blood. However, their technology also could be used to monitor glucose and glutamate quantities as well, Medgadetreported.

“The sensor system successfully generated point-of-care measurements of phenylalanine, glucose, and glutamate. The approach makes any metabolite that can be oxidized by the cofactor a candidate for quantitative point of care assays,” the authors wrote in Science.

As shown above, a mixture of the patient’s blood and the reaction buffer is applied onto a paper covered with the immobilized biosensor. The following reaction is detected with a digital camera and analyzed. (Photo and caption copyrights: Max Planck Institute for Medical Research.)

How it Works

According to an MPIMR online video:

  • A tiny sample of blood (about 0.5 microliters) is taken from a patient’s finger;
  • The sample is added to a reaction buffer;
  • The sample is then applied to the paper assay containing the biosensor;
  • A mounted digital camera or smartphone is used to detect color shift;
  • Color changes from blue to red indicated when phenylalanine is “consumed” and nicotinamide adenine dinucleotide (NADPH) produced;
  • Red is a sign of high Phe concentration and blue low Phe;
  • The assay takes 15 minutes to perform.

“We have developed light-emitting sensor proteins to report the concentration of the cofactor NADPH through which many medical metabolites can be quantified. Because of the bioluminescent nature of the paper, we can capture the signal—even in blood,” Yu states in the video.

This video demonstrates how the new biosensor works. The process the researchers developed for detecting and measure quantities of Phe in blood involves light-emitting engineered protein and the use of a digital camera or smartphone. During the process a color shift takes place that can be measured to determine the amount of Phe in the blood, Engineering 360 explained. Click here to watch the video. (Video copyright: Max Planck Society/YouTube.)

People Need Faster Test Answers

More studies are needed before patients use can use the assay do their own metabolite measurement blood tests. And the scientists say they plan to simplify and automatize the test.

However, the researchers feel such fast measurements are needed since many diseases cause changes in blood metabolites. Conventional clinical laboratory blood tests do help patients to stay on top of their conditions. But the sooner they can get results, the quicker patients can make necessary changes in diet and more, the authors note.

“Monitoring metabolites at the point of care could improve the diagnosis and management of numerous diseases. Yet for most metabolites, such assays are not available. We introduce semisynthetic, light-emitting sensor proteins for use in paper-based metabolic assays,” the researchers wrote in Science.

Medical laboratory leaders may find it interesting to see a POC test with performance similar to tests using sophisticated medical laboratory technology. In fact, Yu makes that point as he stands in front of liquid chromatography-mass spectrometry (LC-MS) equipment in the aforementioned video.

Could the paper-based biosensor one day be preferred by doctors and patients who need to monitor metabolites? People residing in remote or rural areas where patient care centers are not so plentiful may appreciate and need such a tool. And patients may prefer the convenience of doing it themselves and getting fast answers, rather than visiting a clinical laboratory and waiting days for results. Either way, these developments are worth following.

—Donna Marie Pocius

Related Information:

Biosensor for Phenylketonuria: With the Help of a New Blood Test, Patients with This Disease Can Monitor Their Metabolites

Paper Test for Monitoring Phenylalanine and Other Metabolites in Blood

Semisynthetic Sensor Proteins Enable Metabolic Assays at the Point of Care

What are Metabolites?

Facilitating Diagnosis with a New Type of Biosensor

Paper-based Device Monitors Blood Metabolites

Blood Test for Phenylketonuria with Biosensor