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Biosensing Technology Offers Advanced Diagnostic Capabilities

An electronic biosensing platform, combining nanoelectronics and three-dimensional electronic system integration, could replace the conventional microplate.

Electronic biosensing technology could someday displace the multi-welled microplate, long a standard tool in biomedical research and diagnostic laboratories. Essentially arrays of tiny test tubes, microplates have been used for decades to simultaneously test multiple samples for their responses to chemicals, living organisms, or antibodies. Fluorescence or color changes in labels associated with compounds on the plates can signal the presence of particular proteins or gene sequences.

altResearchers hope to replace these microplates with modern microelectronics technology, including disposable arrays containing thousands of electronic sensors connected to powerful signal processing circuitry. If successful, this new electronic biosensing platform could make real-time disease diagnosis possible — potentially in a physician’s office — by helping select individualized therapeutic approaches.

The device could facilitate personalized medicine by detecting the gene mutations that are indicative of cancer and determining treatment. Fundamental to the new biosensing system is the ability to electronically detect markers that differentiate between healthy and diseased cells. These markers could be differences in proteins, mutations in DNA, or even specific levels of ions that exist at different amounts in cancer cells. Researchers are finding more and more differences like these that could be exploited to create fast and inexpensive electronic detection techniques that don’t rely on conventional labels.

The general-purpose sensing platform is being developed using nanoelectronics and three-dimensional electronic system integration to modernize and add new applications to the old microplate application.

The three-dimensional sensor arrays are fabricated using conventional lowcost, top-down microelectronics technology. Though existing sample preparation and loading systems may have to be modified, the new biosensor arrays should be compatible with existing workflows in research and diagnostic labs.

A key advantage of the platform is that sensing will be done using low-cost, disposable components, while information processing will be done by reusable conventional integrated circuits connected temporarily to the array. Ultra-high density spring-like mechanically compliant connectors and advanced “through-silicon vias” will make the electrical connections while allowing technicians to replace the biosensor arrays without damaging the underlying circuitry.

Separating the sensing and processing portions allows fabrication to be optimized for each type of device. Without the separation, the types of materials and processes that can be used to fabricate the sensors are severely limited.

The sensitivity of the tiny electronic sensors can often be greater than current systems, potentially allowing diseases to be detected earlier. Because the sample wells will be substantially smaller than those of current microplates — allowing a smaller form factor — they could permit more testing to be done with a given sample volume.

The technology could also facilitate use of ligand-based sensing that recognizes specific genetic sequences in DNA or messenger RNA.

So far, the researchers have demonstrated a biosensing system with silicon nanowire sensors in a 16-well device built on a one-centimeter by one-centimeter chip. The nanowires, just 50 × 70 nanometers, differentiated between ovarian cancer cells and healthy ovarian epithelial cells at a variety of cell densities.

Silicon nanowire sensor technology can be used to simultaneously detect large numbers of different cells and bio-materials without labels. Beyond that versatile technology, the biosensing platform could accommodate a broad range of other sensors, including technologies that may not exist yet. Ultimately, hundreds of thousands of different sensors could be included on each chip, enough to rapidly detect markers for a broad range of diseases.

Genetic mutations can lead to a large number of different disease states that can affect a patient’s response to disease or medication, but current labeled sensing methods are limited in their ability to detect large numbers of different markers simultaneously.

Mapping single nucleotide polymorphisms (SNPs), variations that account for approximately 90 percent of human genetic variation, could be used to determine a patient’s propensity for a disease, or their likelihood of benefitting from a particular intervention. The new biosensing technology could enable caregivers to produce and analyze SNP maps at the point-of-care.

This technology was done by the Georgia Institute of Technology, Atlanta, Georgia. For more information, visit http://www.gatech.edu.