Functionalized nanopipettes: toward label-free, single cell biosensors

Abstract

Nanopipette technology has been proven to be a label-free biosensor capable of identifying DNA and proteins. The nanopipette can include specific recognition elements for analyte discrimination based on size, shape, and charge density. The fully electrical read-out and the ease and low-cost fabrication are unique features that give this technology an enormous potential. Unlike other biosensing platforms, nanopipettes can be precisely manipulated with submicron accuracy and used to study single cell dynamics. This review is focused on creative applications of nanopipette technology for biosensing. We highlight the potential of this technology with a particular attention to integration of this biosensor with single cell manipulation platforms.

Fig. 1

Schematic representation of the etching process of a sealed nanopipette. a Microscopic image of the sealed micropipette tip. b, c The external etching was monitored via electrochemical measurements until the desired pore size was obtained. Adapted with permission from [20]

Fig. 2

a Geometrical representation of a nanopipette tip. b Bare and c PLL-coated electrical double layer formed at the inner surface of nanopipette electrode in solution and associated current/voltage plots

Fig. 3

Typical nanopipette detection platform

Fig. 4

Schematic representation of a 10-nm gold nanoparticle-labeled oligo. Not to scale

Fig. 5

Statistical distribution of current blockade event amplitudes. Specific signatures of oligo (tail) and nanoparticle (head) blocks are clearly identified. Adapted with permission from [19]

Fig. 6

Adapted results of ref [26] in which the nanopipettes was used as a DNA hybridization sensor. Reproduced by permission of The Royal Society of Chemistry

Fig. 7

Current amplitude changes upon binding of IL-10 and VEGF to anti-IL-10 and anti-VEGF functionalized nanopipettes. Adapted with permission from [34]

Fig. 8

Stepwise blockade of measured currents upon the individual binding event of immunoglobin E (IgE) in assay solution to the anti-IgE aptamer immobilized on the nanopipette surface. Adapted with permission from [33]