Label-free sub-picomolar protein detection with field-effect transistors

A detailed understanding of complex biological systems requires information about the functional state of proteins, which perform the bulk of work in the cell. Proteomics currently plays a major role in many areas of biomedicine, such as the identification of cancer biomarkers. The ability to directly interrogate protein interactions is therefore of major importance. In particular, high throughput protein analysis methods allowing quantitative detection are highly desirable. Sensing devices yielding very low protein detection limits are required for many applications such as clinical diagnostics. Label-free electrical protein detection with sub-picomolar detection limits has been achieved with the use of metal-oxide-semiconductor field-effect transistors (MOSFETs). The gates of the MOSFETs are connected to external gold electrodes, where the protein interactions take place. Upon biomolecular interaction, the induced variations in open circuit potential are measured by means of shifts in the transfer characteristics of the transistors. Our protein test system involves the use of peptide aptamers that recognise highly related protein partners of the cyclin-dependent kinase (CDK) family. Using our technique, human CDK2 has been detected at 100 fM or 5 pg/ml, well within the clinically relevant range. The target specificity, ease of fabrication and scalability of these FET arrays, further demonstrates the potential application of the multiplexable field effect format to protein sensing.