There’s a completely electronic method for barcoding particles according to researchers at Rutgers University. Unlike standard approaches, this method allows for multiplexed bioassays that can be miniaturized down to the size of a micro-chip. Thus, this technology could be included in a handheld device for point-of-care applications or as part of a wearable biosensor that could continuously test for a dozen different biomarkers, such as proteins indicating cancer or molecules that hint at exposure to bacteria, viruses, or even pollutants.

There Is a Need to Analyze Multiple Biomarkers

“Biomarkers” refers to biological molecules (such as proteins or DNA) that can indicate health status or the presence of a disease. Examples include human chorionic gonadotropin (hCG), which is measured in home pregnancy test kits, and prostate-specific antigen (PSA), whose levels can signal the presence of prostate cancer. Point-of-care tests for assaying specific molecules already exist, but correct biomarker-based diagnosis of disease often requires simultaneous measurements of multiple biomarkers.

“One biomarker is often insufficient to pinpoint a specific disease because of the heterogeneous nature of various types of diseases, such as heart disease, cancer and inflammatory disease”, says Mehdi Javanmard, assistant professor and senior author of the study. “To get an accurate diagnosis and accurate management of various health conditions, you need to be able to analyze multiple biomarkers at the same time.”

The development of a compact platform that can carry out sensitive, multiplexed biomarker analysis represents a major breakthrough, that could become an enabling technology for more widespread point-of-care diagnostic tools and wearable platforms for continuous biomarker monitoring.

Standard Barcoding Approaches Are Either Too Large or Too Low-Throughput

For high-throughput applications, optical and plasmonic techniques for barcoding are quite common. An example are barcoded quantum dots, which have seen use in assays for proteins and nucleic acids. However, all of these techniques require large, bulky instrumentation. They are thus well-suited for laboratory research, where the ability to analyze thousands of markers with a high degree of sensitivity enables large-scale discovery applications. However, they are not ideal for on-site applications, where compact versions are a must.

At the other end of the spectrum, electrical impedance and electrochemical-based detection techniques can be miniaturized to create inexpensive devices, but challenges in electronic barcoding have prevented truly multiplexed biomarker assays. Applicability has generally been limited to surface array-based methods (e.g., immunoassays), which are less flexible due to the need for expertise in surface chemistry and the often laborious assay development. Microsphere barcoding provides greater flexibility for selecting the desired molecular biomarkers, but traditional impedance-based methods require use of different bead sizes, which limits multiplexing to just a few different barcodes. What is needed for point-of-care applications is something in between these two extremes: a highly compact, fast, portable sensor that enables multiplexed analysis.

Getting It Just Right: Small Size and High Throughput

This piece of research describes the first impedance-based solution for micro-particle barcoding, which the authors terms nanoelectronic barcoding. The researchers are able to form tunable nano-capacitors on the surface of microspheres. This allows them to distinguish different bead barcodes associated with microspheres that have been engineered to detect specific biomarkers. Importantly, the results can be analyzed using an ultra-compact electronic detector. According to Javanmard, “This is really important in the context of personalized medicine or personalized health monitoring. Our technology enables true labs on chips. We’re talking about platforms the size of a USB flash drive or something that can be integrated onto an Apple Watch, for example, or a Fitbit.”

The technology was found to be over 95 percent accurate in identifying biomarkers, and the researchers are working to further improve this number to 100 percent. This study does represent just a small-scale demonstration of the feasibility of electronic barcoding for multiplexed assays. Only 4 different particle types were differentiated in this study, but the authors speculate that optimization of fabrication, tuning of multiple parameters, and further statistical analysis (including classification by machine learning) could enable up to 30 unique barcodes. Technological limitations inherent to electrical impedance measurements will make higher throughputs difficult to achieve, but this lower level of just dozens of biomarkers could be acceptable for most point-of-care and wearable applications.

Innovation to Market

This technology will not supersede the other techniques described above, but will rather fill an important niche that is unmet by conventional approaches. For assays whose goal is biomarker discovery and validation, the high throughput of optical barcoding (allowing for thousands of barcodes) will be best. However, for portable applications where tens of barcodes are sufficient to provide meaningful insights into an individual’s overall health or diagnosis of a particular disease condition, nanoelectronic barcoding could become the new standard. “Imagine a small tool that could analyze a swab sample of what’s on the doorknob of a bathroom or front door and detect influenza or a wide array of other virus particles,” says Javanmard. “Imagine ordering a salad at a restaurant and testing it for E. coli or Salmonella bacteria.” The researchers claim that such a tool could be commercially available within the next two years, with full applications for health monitoring and diagnostic tools available as early as five years from now.

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