Impedance derived electroanalytical assays are inherently spectroscopic (frequency resolved) and potentially exceedingly sensitive indicators of interfacial change (such as target binding at an appropriate receptor). We introduce here the use of a portfolio of mathematically derived immittance functions and related components, capable, from the same raw data sets, of enabling increased assay sensitivity and markedly shorter assay times in comparison to traditional impedance analyses. The methodology, applied herein to faradaic (redox probe amplified) and non-faradaic assays, requires no equivalent circuit analysis or prior assumption of response. Its focus is to optimize analytical potency and to enable the user to select and apply the most frequency-optimized reporter of interfacial change and to, thereafter, run rapid (optimized) analyses at single frequencies.

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An electrode surface confined redox group contributes to a substantial potential-dependent interfacial charging that can be sensitively probed and frequency-resolved by impedance-derived capacitance spectroscopy. In utilizing the sensitivity of this charging fingerprint to redox group environment, one can seek to generate derived sensory configurations. Exemplified here through the generation of mixed molecular films comprising ferrocene and antibody receptors to two clinically important targets, the label-free methodology is able to report on human prostatic acid phosphatase (PAP), a tumor marker, with a limit of detection of 11 pM and C-reactive protein with a limit of detection of 28 pM. Both assays exhibit linear ranges encompassing those of clinical value.

The application of nanoscale capacitance as a transduction of molecular recognition relevant to molecular diagnostics is demonstrated. The energy-related signal relates directly to the electron occupation of quantized states present in readily fabricated molecular junctions such as those presented by redox switchable self-assembled molecular monolayers, reduced graphene oxide or redox-active graphene composite films, assembled on standard metallic or micro-fabricated electrodes. Sensor design is thus based on the response of a confined and resolved electronic density of states to target binding and the associated change in interfacial chemical potential. Demonstrated herein with a number of clinically important markers, this represents a new potent and ultrasensitive molecular detection enabling energy transducer principle capable of quantifying, in a single step and reagentless manner, markers within biological fluid.