Label-free direct detection of biomolecular analytes from optically inaccessible samples.

摘要

Fluorescent optical methods for biomolecular detection are widely used for research and diagnostic applications. However, these techniques are useful only in sample matrices that are optically transparent non-scattering, which precludes most biologically relevant fluids, such as blood, urine, and saliva. Errors are introduced by the manipulations and purification steps necessary to prepare biological samples for analysis, as well as by the labeling and amplification steps required for low-abundance analytes. As a result, almost all diagnostic procedures must be performed in resource-intensive laboratories with highly-trained technicians. This limits not only wide-spread access to many tests, but also the capacity of the healthcare infrastructure to accommodate epidemics. For this reason, many efforts have been made over the past few decades to develop label-free, non-optical methods for performing biological testing. We report here a nanoelectronic transistor platform that overcomes limitations of optical techniques by eliminating labels, as well as surpasses other electrochemical and electronic technologies with respect to "noise." By coupling analyte-specific biological receptors to single-electron transistor (SET) arrays, a simple, label- free, real-time, non-optical platform is created that can analyze biological samples quantitatively from real-world samples, such as blood, urine, or saliva. Dynamic range is scalable by increasing the number of transistors coupled to the same type of receptor. Binding-induced electrostatic fluctuations in the molecular probe molecule serve to "gate" the conductivity of an SET affording a direct measure of the molecular binding state. Quantitative measurement of analyte concentration is achieved by counting the ratio of bound to unbound receptors as a function of time. The measurement of binding rate can also be used as a means of distinguishing specific versus non- specific cross-reactivity of similar molecules from complex mixtures.