Field-Effect Sensors for Virus Detection: From Ebola to SARS-CoV-2 and Plant Viral Enhancers

Abstract

Coronavirus disease 2019 (COVID-19) is a novel human infectious disease provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, no specific vaccines or drugs against COVID-19 are available. Therefore, early diagnosis and treatment are essential in order to slow the virus spread and to contain the disease outbreak. Hence, new diagnostic tests and devices for virus detection in clinical samples that are faster, more accurate and reliable, easier and cost-efficient than existing ones are needed. Due to the small sizes, fast response time, label-free operation without the need for expensive and time-consuming labeling steps, the possibility of real-time and multiplexed measurements, robustness and portability (point-of-care and on-site testing), biosensors based on semiconductor field-effect devices (FEDs) are one of the most attractive platforms for an electrical detection of charged biomolecules and bioparticles by their intrinsic charge. In this review, recent advances and key developments in the field of label-free detection of viruses (including plant viruses) with various types of FEDs are presented. In recent years, however, certain plant viruses have also attracted additional interest for biosensor layouts: Their repetitive protein subunits arranged at nanometric spacing can be employed for coupling functional molecules. If used as adapters on sensor chip surfaces, they allow an efficient immobilization of analyte-specific recognition and detector elements such as antibodies and enzymes at highest surface densities. The display on plant viral bionanoparticles may also lead to long-time stabilization of sensor molecules upon repeated uses and has the potential to increase sensor performance substantially, compared to conventional layouts. This has been demonstrated in different proof-of-concept biosensor devices. Therefore, richly available plant viral particles, non-pathogenic for animals or humans, might gain novel importance if applied in receptor layers of FEDs. These perspectives are explained and discussed with regard to future detection strategies for COVID-19 and related viral diseases.

3D-Printed COVID-19 immunosensors with electronic readout

“…To date, several electrochemical immunosensing strategies ( i.e. , label-free, sandwich, direct/competitive or lateral-flow assays) have been devised for the rapid determination and quantification of different viruses [13] , [14] , [15] , [16] , also including the SARS-CoV-2 [17] , [18] , [19] , [20] , [21] .…”

Capacitive Field-Effect Biosensor Studying Adsorption of Tobacco Mosaic Virus Particles

“…To overcome these limitations and thus to enhance the sensor performance, various strategies have been proposed recently. Examples are measurements in a low ionic-strength solution in order to reduce the influence of the counter-ion screening effect, or the use of agents to block non-specific adsorption, just to name a few (see, e.g., [ 43 , 49 ]).…”

“…These first successful experiments underline the potential to integrate TMV/bioreceptor hybrids with electronic transducers. Since field-effect sensors are able to directly convert specific (bio)molecular interactions into electrical signals, they have been widely applied such as for the detection of enzymatic reactions, cell acidification and cellular signals, DNA (deoxyribonucleic acid), antibody-antigen affinity binding, neurotransmitters, and viruses (see e.g., [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]). The functionalization of field-effect sensors with TMV nanocarriers enables a universal approach to engineer a large variety of biosensors and biochips.…”

Parallel Potentiometric and Capacitive Response in a Water-Gate Thin Film Transistor Biosensor at High Ionic Strength

“…Following the invention of the ‘ion-sensitive field effect transistor’ (ISFET) by Bergveld in 1970 [ 1 ], the sensor community has developed an entire ‘family’ of field effect-based potentiometric sensors for waterborne (aqueous) analytes. This now includes field effect sensors for biomedical analytes far beyond the initial cations, with wide applications as ‘BioFETs’, reviewed e.g., in [ 2 , 3 ]. In the ISFET concept, a sensitive element (‘sensitiser’, ‘receptor’, or ‘recognition element’) is applied to the gate contact or the semiconducting film of a thin film field effect transistor (TFT) that acts as a transducer when operated and characterised while in contact with an aqueous medium.…”