Field effect transistor (FET)-based biosensors could be ideal for next-generation point-of-care diagnostics because they can detect biomolecules quickly, are inexpensive and can be mass-fabricated using conventional nano- and microfabrication processes. They are also highly sensitive and allow for label-free detection of a variety of analytes, including electrolyte ions, DNA, small molecules, proteins and cells. However, despite all these good properties there are not many commercial FET biosensors on the market today. This is because they do suffer from one major drawback: the “Debye screening” problem in physiological solutions.

FET-based biosensors work by detecting the change in electric field produced when charged target species bind to the sensor surface. This results in changes in the channel current that can then be measured. The analyte charge can be masked, or screened, however by electrolyte ions, especially in liquids in which the ion concentration is high, such as blood or serum, explains team leader Alexey Tarasov of BioMed X Innovation Center in Heidelberg. The signals produced thus become very small as a result.

Reducing the screening effect

Tarasov and colleagues have now succeeded in strongly enhancing the signal from a target molecule by, among other things, modifying the sensor surface using short specific receptors (antibody fragments) and polymer molecules (polyethylene glycol) on a gold surface.

“The short receptors bring the analyte closer to the surface of the sensor and thereby help increase the signal,” Tarasov told nanotechweb.org. “It is not yet clear how exactly the polymer molecules enhance the signal but we think that they may change the local dielectric environment and effectively reduce the screening effect. More work is still needed though to fully understand the effect.”

Device could be extended to many other biomolecules

To test their device, the researchers chose to detect human thyroid-stimulating hormone as a model analyte because it is a well-characterized, clinically important hormone that needs to be detected in low concentrations. “We were able to reliably detect concentrations as low as 500 femtomolar in whole serum,” says Tarasov. “The sensor also covers a very large analyte concentration range up to 100 nanomolar. We think that our concept is quite general and might be extended to many other biomolecules by changing the specific receptors on the surface of the sensor.”

First transistor-based biosensor to work in whole serum

To the best of our knowledge, this is the first transistor-based biosensor to detect low concentrations of biomolecules in whole serum without the need for sample pre-treatment, labelling or washing steps, he adds. It is low-cost, compact and can easily be integrated into portable diagnostics devices.

The researchers, reporting their work in ACS Sensors DOI: 10.1021/acssensors.7b00187, say that they will now be focusing on optimizing their device so that it can detect even lower levels of biomolecules. “We will also be testing it out on real patient samples, including whole blood samples, and looking at how accurate it is compared to state-of-the-art analysers.”