Universal scaling theory of electrochemical immunosensors: An analytical approach to define and compare performance metrics

Abstract

Electrochemical immunosensors have emerged as a versatile, sensitive, and selective sensor technology of choice for a variety of applications, including detection of proteins, food pathogens, bacteria, viruses, and cancerous molecules. The combination of highly specific biorecognition elements and electrical readout systems facilitates the detection of antigens down to femtomolar concentrations. However, a lack of quantitative theoretical framework has made the design, optimization, and comparison of sensors difficult, without a clear and definitive understanding of the limits of detection, dynamic range, and sensitivity. In this paper, we integrate reaction-diffusion and effective media theories to derive a generalized scaling model for an arbitrary immunosensor that relates the relative change of redox current to the corresponding change in antigen concentration, through scaling exponents related to the geometry of biomolecules diffusion and the measurement resolution. Experimental data from dozens of immunosensors (for a variety of antigens, material systems, and sensor geometry) validate our sensor-agnostic scaling formula. Our results would allow cross-calibration of the emerging and traditional immunosensors reported across the literature and define a physics-based, standardized methodology to compare performance metrics, such as limits of detection, dynamic range, and sensitivity.

A Simultaneous Calibration and Detection Strategy for Electrochemical Sensing with High Accuracy in Complex Water

“…The nitrite concentration of these two samples should fall within the linear range and as close as possible to C x in order to form a shrunken linear range compared to that in commonly used laboratory calibration, thus reducing the error brought by nonlinearity. 14 Besides, V 1 should be close to V in order to ensure the copollutant matrices in the diluted sample and the nitriteadded sample are similar to those in the actual sample. Consequently, C add was determined to be 200 μM and V − V 1 was optimized through the following referencing experiments.…”

“…12 Electrochemical sensing, which is based on oxidation or reduction between the sensing electrode and a target contaminant, produces an electrical signal proportional to the pollutant concentration. 13,14 In recent years, many sensing materials have been developed to expand the detection range, lower the LOD, and improve the selectivity. 15−17 However, the practical water body is a complex system that might contain various electrochemically sensitive ions and organics, with fluctuating temperature and pH value, which could lead to deviation or cross-sensitivity for electrochemical sensing.…”

Wearable Sensor Patch with Hydrogel Microneedles for In Situ Analysis of Interstitial Fluid

“…The MNs were depicted with a blunted shape rather than an idealized conical form to emphasize the significance of the effective tip radius ( s tip ) in modeling. Second, as displayed in the circuit analogy, each domain was modeled with a diffusive resistor ( R i in s m –3 ), in line with the theory of effective media formulation, to approximate the transport of the analyte molecule across the domains . From a phenomenological perspective, the analyte absorption across the MN tip and base is comparable to ion uptake by bacteria, while the transport along the MN length and the bulk hydrogel patch resembles the spreading resistance of a point contact .…”

“…Second, as displayed in the circuit analogy, each domain was modeled with a diffusive resistor (R i in s m −3 ), in line with the theory of effective media formulation, to approximate the transport of the analyte molecule across the domains. 46 From a phenomenological perspective, the analyte absorption across the MN tip and base is comparable to ion uptake by bacteria, 47 while the transport along the MN length and the bulk hydrogel patch resembles the spreading resistance of a point contact. 48 Lastly, the resistance was multiplied by the corresponding volume of transported biofluid (V i in m 3 ) to determine the delay time across each domain (t i = R i V i ).…”

The Emergence of Microneedle-Based Smart Sensor/Drug-Delivery Patches: A Scaling Theory Defines the Tradeoff between the Response Time and the Limits of Detection

“…Smart healthcare, powered by ultra-scaled, and always-on digital electronics and wearable and implantable (WI) sensors, marks an exciting frontier in modern medicine. Technological advancements, including microfabrication, miniaturization, portability, low power, and cost-effectiveness, have shifted testing sites from traditional laboratories to "under or on skin" platforms [1][2][3][4].…”