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Glass nanopipette has gained widespread use as a versatile single-entity detector in chemical and biological sensing, analysis, and imaging. Its advantages include low cost, easy accessibility, simplicity of use, and high versatility. However, conventional nanopipettes based on the volume exclusion mechanism have limitations in detecting small biomolecules due to their small volume and high mobility in aqueous solution. To overcome this challenge, we have employed a novel approach by capitalizing on the strong nanoconfinement effect of nanopipette. This is achieved by utilizing both the hard confinement provided by the long taper nanopipette tip at the cis side and the soft confinement offered by the hydrogel at the trans side. Through this approach we have effectively slowed down the exit motion of small molecules, allowing us to enrich and jam them at the nanopipette tip. Consequently, we have achieved high throughput detection of small biomolecules with sizes as small as 1 nm, including nucleoside triphosphates, short peptides, and small proteins with excellent signal-to-noise ratios. Furthermore, molecular complex formation through specific intermolecular interactions, such as hydrogen bonding between closely spaced nucleotides in the jam-packed nanopipette tip, have been detected based on the unique ionic current changes. 

We report an experimental demonstration of optical two-dimensional coherent spectroscopy (2DCS) in cold atoms. The experiment integrates a collinear 2DCS setup with a magneto-optical trap (MOT), in which cold rubidium (Rb) atoms are prepared at a temperature of approximately 200 µK and a number density of 10¹⁰cm⁻³. With a sequence of femtosecond laser pulses, we first obtain one-dimensional second- and fourth-order nonlinear signals and then acquire both one-quantum and zero-quantum 2D spectra of cold Rb atoms. The capability of performing optical 2DCS in cold atoms is an important step toward optical 2DCS study of many-body physics in cold atoms and ultimately in atom arrays and trapped ions. Optical 2DCS in cold atoms/molecules can also be a new avenue to probe chemical reaction dynamics in cold molecules.