Researchers at Purdue University have achieved a breakthrough in biosensor technology which could yield personalized diagnostic chips many hundreds of times more sensitive than current technology.

Flexure FET biosensor combines a mechanical sensor, which identifies a biomolecule based on its mass or size, with an electrical sensor that identifies molecules based on their electrical charge.

“Individually, both of these types of biosensors have limited sensitivity, but when you combine the two you get something that is better than either,” said Muhammad A. Alam, professor of electrical and computer engineering at Purdue University.

Two potential applications are for personalized medicine, in which an inventory of proteins and DNA is recorded for individual patients to make more precise diagnostics and treatment decisions, and the early detection of cancer and other diseases.

For early cancer diagnostics the sensor makes possible the detection of small quantities of DNA fragments and proteins deformed by cancer long before the disease is visible through imaging or other methods.

In other mechanical biosensors, a laser measures the vibrating frequency or deflection of the cantilever, which changes depending on what type of biomolecule lands on the cantilever. The cantilever is biased using an electric field to pull it downward as though with an invisible string. Instead of using a laser, the new sensor uses the transistor to measure the vibration or deflection. The sensor maximizes sensitivity by putting both the cantilever and transistor in a “bias”.

 

The device also eliminates the need for a “reference electrode,” which is a required component for conventional electrical biosensors but cannot be miniaturized, limiting practical applications. “Eliminating the need for a reference electrode enables miniaturization and makes it feasible for low-cost, point-of-care applications in doctor’s offices,” said Alam.

It will likely be several years before we see a practical application of this technology, but it’s an exciting development for personalized medicine none the less. To bring diagnostic technology with this level of sensitivity to the bed-side is truly the holy grail of 21st century medicine.

The work has been funded by the U.S. Department of Defense, U.S. Department of Energy, National Institutes of Health-PRISM center at Purdue’s Discovery Park, and the Semiconductor Research Consortium through the MSD center at the Massachusetts Institute of Technology.

ABSTRACT

Flexure-FET Biosensor to Break the Fundamental Sensitivity Limits of Nanobiosensors Using Nonlinear Electro-Mechanical Coupling

Ankit Jain*, Pradeep R. Nair and Muhammad A. Alam#

School of ECE, Purdue University

In this letter, we propose a Flexure-FET (Flexure sensitive Field Effect Transistor) ultrasensitive biosensor that utilizes the nonlinear electro-mechanical coupling to overcome the fundamental sensitivity limits of classical electrical or mechanical nanoscale biosensors. The stiffness of the suspended gate of Flexure-FET changes with the capture of the target bio-molecules, and the corresponding change in the gate shape or deflection is reflected in the drain current of FET.

The Flexure-FET is configured to operate such that the gate is biased near pull-in instability, and the FET-channel is biased in the sub-threshold regime. In this coupled nonlinear operating mode, the sensitivity (S) of Flexure-FET with respect to the captured molecule density (Ns) is shown to be exponentially higher than that of any other electrical or mechanical biosensor. In addition, the proposed sensor can detect both charged and charge-neutral bio-molecules, without requiring a reference electrode or any sophisticated instrumentation, making it a potential candidate for various low-cost, point-of-care applications.