Biomembrane-Modified Field Effect Transistors for Sensitive and Quantitative Detection of Biological Toxins and Pathogens

Abstract

The efforts of detecting bioactive targets with complex, dynamic, and unknown molecular profiles have inspired the development of various biosensor platforms. Herein, we report a cell-membrane-modified field effect transistor (FET) as a function-based nanosensor for the detection and quantitative measurement of numerous toxins and biological samples. By coating carbon nanotube FETs with natural red blood cell membranes, the resulting biomimetic nanosensor can selectively interact with and absorb broad-spectrum hemolytic toxins regardless of their molecular structures. Toxin–biomembrane interactions alter the local charge distribution at the FET surface in an ultrasensitive and concentration-dependent manner, resulting in a detection limit down to the femtomolar (fM) range. Accurate and quantitative measurements are enabled via a built-in calibration mechanism of the sensor, which overcomes batch-to-batch fabrication variations, and are demonstrated using three distinct toxins and various complex bacterial supernatants. The measured signals of bacterium-secreted proteins correlate linearly with the actual bacterial numbers, making the biosensor a nontraditional approach to rapidly detecting bacterial concentrations without a need to count bacterial colonies.

Design of Hierarchical Beads for Efficient Label‐Free Cell Capture

“…Here we used HA to functionalize the surface of hierarchical beads due to the surface hydrophilicity, biocompatibility, and chemical/structural stability. For surface hydrophilicity, the initial HB‐1000/500/150 were hydrophobic due to nanoscale surface roughness trapping nanosized air bubbles3a,15b,20 and the functionalized HHB‐1000/500/150 were hydrophilic due to the abundant carboxy groups (Figure d) retaining water molecules 13a,21. For biocompatibility, the HA‐modified beads showed lower cellular toxicity compared to the pristine hierarchical beads with unmodified surface (Figure S7, Supporting Information), consistent with previous reports 15c,22.…”

“…For surface hydrophilicity, the initial HB‐1000/500/150 were hydrophobic due to nanoscale surface roughness trapping nanosized air bubbles3a,15b,20 and the functionalized HHB‐1000/500/150 were hydrophilic due to the abundant carboxy groups (Figure d) retaining water molecules 13a,21. For biocompatibility, the HA‐modified beads showed lower cellular toxicity compared to the pristine hierarchical beads with unmodified surface (Figure S7, Supporting Information), consistent with previous reports 15c,22. For chemical/structural stability, the HHB‐1000/500/150 were stable in both composition (Figure d) and structure (Figure e) without obvious changes under aqueous solutions which would be ideal for the following cell capture experiments.…”

“…Compared to the labeling process that needs specific probes (such as antibodies), label‐free cell capture represents the next generation tool and usually requires smart materials or devices 6c,13. Ideal materials and devices for efficient label‐free cell capture may offer: 1) surface topology with strong adherence to cell membranes; 2) surface chemistry with high biocompatibility and affinity;3c,12a,15 3) specific size to avoid cellular endocytosis; and 4) structural stability during the whole cell capture process 6c,11b,12a,17. Until now, most existing label‐free techniques only addressed parts of these issues and usually applied in imaging or delivery.…”

Hybrid Lipid-Polymer Bilayers: pH-Mediated Interactions between Hybrid Vesicles and Glass

“…The natural solution to this puzzle was to explore the adsorption behavior of polymer and hybrid vesicles as a function of pH. Using vesicles with a range in composition from pure DOPC to pure EO 22 Bd 33 (10,25,50,75, and 100 mol % polymer) we probed the interaction of hybrid vesicles with glass under varying pH conditions (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) by measuring changes in frequency and dissipation (Figure 4). We first compared QCM-D data from hybrid vesicles interacting with glass at pH = 2 to the results obtained at pH = 7 (see above).…”

“…Sensors that incorporate biomacromolecules involved in receptor binding or molecular traffic across membranes would be highly tunable and have the potential for sensing with the sensitivity and specificity of biological structures. Indeed, biosensors based on lipid bilayer membranes have demonstrated ways to interrogate membrane-based biochemical processes optically [4], electrically [2,3,5], and acoustically [6][7][8][9].…”