Abstract
Nanofluidics, a discipline of science and engineering of fluids confined to structures at the 1–1000 nm scale, has experienced significant growth over the past decade. Nanofluidics have offered fascinating platforms for chemical and biological analyses by exploiting the unique characteristics of liquids and molecules confined in nanospaces; however, the difficulty to detect molecules in extremely small spaces hampers the practical applications of nanofluidic devices. Laser-induced fluorescence microscopy with single-molecule sensitivity has been so far a major detection method in nanofluidics, but issues arising from labeling and photobleaching limit its application. Recently, numerous label-free detection methods have been developed to identify and determine the number of molecules, as well as provide chemical, conformational, and kinetic information of molecules. This review focuses on label-free detection techniques designed for nanofluidics; these techniques are divided into two groups: optical and electrical/electrochemical detection methods. In this review, we discuss on the developed nanofluidic device architectures, elucidate the mechanisms by which the utilization of nanofluidics in manipulating molecules and controlling light–matter interactions enhances the capabilities of biological and chemical analyses, and highlight new research directions in the field of detections in nanofluidics.
Highlights
Over the past three decades, microfluidics and the integrated micro chemical systems on a chip have had a great impact on chemical analysis, synthesis, biosciences, and technologies [1,2,3]
Nanofluidics is much more than the scaling down of microfluidics, because fluids on this size scale exhibit specific characteristics that are not observed on the microscale or in bulk
Several ion transport phenomena that are absent or negligible in large microchannels become dominant in nanochannels, such as the localized enhancement of the electric field, the overlap of the electric double layer (EDL) that results in the ion selectivity [5]
Summary
Over the past three decades, microfluidics and the integrated micro chemical systems on a chip have had a great impact on chemical analysis, synthesis, biosciences, and technologies [1,2,3]. The physical confinement and denaturation of DNA molecules in nanofluidic channels has enabled the engineering of single DNA molecules [6]. Besides the novel functions originated from unique properties of fluids on nanoscale, confinement and localization of molecules in nanochannel facilitate high-throughput single-molecule analyses as well as droplet and microwell techniques. The low labeling efficiency significantly impedes the detection of a single molecule or countable number of molecules in nanofluidic channels. The whole field of label-free detections is wide, beyond the scope of this review, state-of-the-art methods applicable or targeted to nanofluidics are summarized ; these detection methods are mainly categorized into optical and electrical/electrochemical methods. The nanofluidics-based manipulation of molecules and control of light–matter interactions to enhance the overall detection performance are emphasized, and potential advances of label-free detections in nanofluidics toward biological and chemical analyses are discussed
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