Going beyond the Debye Length: Overcoming Charge Screening Limitations in Next-Generation Bioelectronic Sensors

Abstract

Electronic biosensors are a natural fit for field-deployable diagnostic devices because they can be miniaturized, mass produced, and integrated with circuitry. Unfortunately, progress in the development of such platforms has been hindered by the fact that mobile ions present in biological samples screen charges from the target molecule, greatly reducing sensor sensitivity. Under physiological conditions, the thickness of the resulting electric double layer is less than 1 nm, and it has generally been assumed that electronic detection beyond this distance is virtually impossible. However, a few recently described sensor design strategies seem to defy this conventional wisdom, exploiting the physics of electrical double layers in ways that traditional models do not capture. In the first strategy, charge screening is decreased by constraining the space in which double layers can form. The second strategy uses external stimuli to prevent double layers from reaching equilibrium, thereby effectively reducing charge screening. In this Perspective, we describe these relatively new concepts and offer theoretical insights into mechanisms that may enable electronic biosensing beyond the Debye length. If these concepts can be further developed and translated into practical electronic biosensors, we foresee exciting opportunities for the next generation of diagnostic technologies.

Accelerated Electron Transfer in Nanostructured Electrodes Improves the Sensitivity of Electrochemical Biosensors

“…It has been shown that limiting the Debye volume at an electrode surface extends the EDL farther into the solution, thereby lessening the extent of electric field screening at that interface. [ 43 , 44 ] Consequently, the stronger electric fields within the nanopores increase the probability of a faradaic electron transfer event for a given conformation of an aptamer probe. Indeed, because of their high density of nanoscale features, nanoporous electrodes offer exactly the type of interface where screening is weaker and where we would predict faradaic electron transfer to be accelerated ( Figure 3 ).…”

Emerging Biosensors to Detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Review

“…For example, in [ 41 ], the 10 mM PBS buffer was diluted to 0.01 mM, which increased the Debye length from 0.7 nm to 7 nm, comparable to the size of the positive-charged spike protein S1 subunit antibody (7–10 nm). However, dilution makes it difficult to detect low-abundance analytes [ 117 , 118 ].…”

Clinically oriented Alzheimer's biosensors: expanding the horizons towards point-of-care diagnostics and beyond

“…For instance, aptamer is useful to overcome the Debye-Hückel screening effect in eld-effect transistor (FET)-based biosensor (vide infra), which commonly hinder the electrical signal from the target molecules under high concentrations of such ions. 79 FET, integrated with proper biorecognition elements such as aptamer or antibody, is a unique and useful sensing device to detect biomolecular targets [80][81][82] offering many advantages such as real-time, highly sensitive, specic, and label-free transduction of biochemical signals. 83,84 In principle, the sensing mechanism of an FET device involves structural and functional integration of biorecognition element in which the selective interaction of bioreceptors and analyte produces changes in biophysical and biochemical signal.…”

“…Another vast obstacle of FET in clinical biosensing measurement relies on the high concentration of salts/buffers in clinical sample-induced Debye-Hückel screening effect. 79 Debye-Hückel effect is the discussion about the correlation of Debye length and unambiguous selective detection of macromolecules. Debye length (l D ) corresponds to the distance measured from FET-biosensor surface and electrolytic buffer solution (e.g., phosphate-buffered saline) describing the screening of surface charges by ions in an electrolyte solution.…”