Direct, Label-Free, and Rapid Transistor-Based Immunodetection in Whole Serum

Transistor-based biosensors fulfill many requirements posed upon transducers for future point-of-care diagnostic devices such as scalable fabrication and label-free and real-time quantification of chemical and biological species with high sensitivity. However, the short Debye screening length in physiological samples (<1 nm) has been a major drawback so far, preventing direct measurements in serum. In this work, we demonstrate how tailoring the sensing surface with short specific biological receptors and a polymer polyethylene glycol (PEG) can strongly enhance the sensor response. In addition, the sensor performance can be dramatically improved if the measurements are performed at elevated temperatures (37 °C instead of 21 °C). With this novel approach, highly sensitive and selective detection of a representative immunosensing parameterhuman thyroid-stimulating hormoneis shown over a wide measuring range with subpicomolar detection limits in whole serum. To the best of our knowledge, this is the first demonstration of direct immunodetection in whole serum using transistor-based biosensors, without the need for sample pretreatment, labeling, or washing steps. The presented sensor is low-cost, can be easily integrated into portable diagnostics devices, and offers a competitive performance compared to state-of-the-art central laboratory analyzers

Label-Free Immunodetection in High Ionic Strength Solutions Using Carbon Nanotube Transistors with Nanobody Receptors

Nanomaterial-based field-effect transistors (FETs) have been proposed for real-time, label-free detection of various biological species. However, screening of the analyte charge by electrolyte ions (Debye screening) has so far limited their use in physiological samples. Here, this challenge is overcome by combining FETs based on single-walled semiconducting carbon nanotube networks (SWCNTs) with a novel surface functionalization comprising: (1) short nanobody receptors, and (2) a polyethylene glycol layer (PEG). Nanobodies are stable, easy-to-produce, short biological receptors (~2–4 nm) that enable analyte binding closer to the sensor surface. The addition of PEG enhances the signal in high ionic strength environment. Using green fluorescent protein (GFP) as a model antigen, high selectivity and sub-picomolar detection limit with a dynamic range exceeding 4 orders of magnitude is demonstrated in physiological solutions. The presented immunoassay is fast, label-free, does not require any sample pre-treatment or washing steps