Metabolomics on a chip: multiple metabolomic measurements for precision medicine
Published: 12 January 2018
Miniaturised techniques to rapidly and simultaneously measure numerous metabolites for point of care implementation are lacking. This project focusses on the creation of a new device that will make it possible, for the first time, to simultaneously measure up to six biomarkers associated with cardiovascular disease (CVD) using a single microchip.
Miniaturised techniques to rapidly and simultaneously measure numerous metabolites for point of care implementation are lacking. This project focuses on the creation of a new device that will make it possible, for the first time, to simultaneously measure up to six biomarkers associated with cardiovascular disease (CVD) using a single microchip.
Metabolomics is the simultaneous measurement of many small molecule metabolites at the same time. Metabolite measurements in medicine have been critical to diagnosis of various diseases: glucose for diabetes, for example, or cholesterol as a risk factor for CVD. As it has become possible to measure more metabolites, using the techniques of mass spectrometry (MS) or nuclear magnetic resonance (NMR), so it is growing evident that levels of other metabolites are also indicative of different diseases. However, MS and NMR depend upon expensive equipment that requires placing within dedicated settings. A team led by David Cumming in Electronic Engineering, Mike Barrett at Glasgow Polyomics and Jesse Dawson in the Institute of Cardiovascular and Medical Science have been working on a totally new way of quantifying metabolites using what will ultimately be a cheap, versatile manner.
Enzymes, which are highly specific for individual metabolites, offer a means to quantify individual metabolites. However, classical enzyme assays involve large, non-versatile equipment such as spectrophotometers. A team of engineers and biologists have been working hard to show how enzyme assays can also be picked up on simple silicon microchip surfaces with an array of different sensors. Enzyme reactions that produce protons or hydrogen peroxide can be monitored using specialised sensors known as ISFETs and photodiodes respectively.
The signals are converted to electronic outputs that are read using an App through a simple smartphone app and the miniature hand held device can be linked directly to a smart phone or tablet to view results. Since the production of these reaction side products is directly proportional to the quantity of the enzymes' metabolite substrates, it offers a means to measure the levels of those substrates in a body fluid. Starting with single metabolites, we then showed we could measure two on the same chip and have now reached four simultaneous measurements for glucose, cholesterol, xanthine and sarcosine. With four metabolites now measured the next challenge is to work with engineering design specialists to add ever more enzymes to the same chip surface.
Mike Barrett, who directs Glasgow Polyomics, where a metabolomics facility has been involved in seeking biomarkers for a range of diseases using their state of the art mass spectrometry platform says that "we believe the technology that we are a developing has the potential to revolutionise metabolomics. A typical mass spectrometer used in metabolomics measurements costs in the order of £500,000 or more, hence the ability to produce a silicon chip based device that can be used for diagnosis of disease will offer a huge breakthrough towards implementation of widespread measurements in disease.
David Cumming, who leads the project which has been central to his EPSRC programme "The Multicorder" says that "I'm delighted to see how our sensor platforms based on silicon have proven sufficiently versatile to offer new ways to sequence DNA through the Ion torrent platform, and now also metabolites with the technology we're developing".
Jesse Dawson, a consultant physician specialising in Stroke medicine adds "we have been using mass spectrometry based platforms to identify new metabolic biomarkers for stroke, and the potential to have a versatile handheld device to measure metabolites in any health setting is incredibly exciting".
The team are now hopeful for a next tranche of funding to enable them to take the concept to the next level.
Figure. The prototypical hand held device linked to a tablet showing the simultaneous measurement of four metabolites whose abundance can help diagnose cardiovascular disease.
First published: 12 January 2018