Precise photoelectrochemical tuning of semiconductor microdisk lasers

Micro-and nanodisk lasers have emerged as promising optical sources and probes for on-chip and free-space applications.However,the randomness in disk diameter introduced by standard nanofabrication makes it challenging to obtain deterministic wavelengths.To address this,we developed a photoelectrochemical(PEC)etching-based technique that enables us to precisely tune the lasing wavelength with subnanometer accuracy.We examined the PEC mechanism and compound semiconductor etching rate in diluted sulfuric acid solution.Using this technique,we produced microlasers on a chip and isolated particles with distinct lasing wavelengths.These precisely tuned disk lasers were then used to tag cells in culture.Our results demonstrate that this scalable technique can be used to produce groups of lasers with precise emission wavelengths for various nanophotonic and biomedical applications.

Laser particles with omnidirectional emission for cell tracking

The ability to track individual cells in space over time is crucial to analyzing heterogeneous cell populations.Recently,microlaser particles have emerged as unique optical probes for massively multiplexed single-cell tagging.However,the microlaser far-field emission is inherently direction-dependent,which causes strong intensity fluctuations when the orientation of the particle varies randomly inside cells.Here,we demonstrate a general solution based on the incorporation of nanoscale light scatterers into microlasers.Two schemes are developed by introducing either boundary defects or a scattering layer into microdisk lasers.The resulting laser output is omnidirectional,with the minimum-to-maximum ratio of the angle-dependent intensity improving from 0.007(-24 dB)to>0.23(-6dB).After transfer into live cells in vitro,the omnidirectional laser particles within moving cells could be tracked continuously with high signal-to-noise ratios for 2 h,while conventional microlasers exhibited frequent signal loss causing tracking failure.

Multiplexed laser particles for spatially resolved single-cell analysis

Biomolecular analysis at the single-cell level is increasingly important in the study of cellular heterogeneity and its consequences,particularly in organismic development and complex diseases such as cancer.Single-cell molecular analyses have led to the identification of new cell types1 and the discovery of novel targets for diagnosis and therapy2.While these analyses are performed predominantly on dissociated single cells,emerging techniques seek understanding of cellular state,cellular function and cell–cell interactions within the native tissue environment by combining optical microscopy and single-cell molecular analyses.These techniques include in situ multiplexed imaging of fluorescently labeled proteins and nucleotides,as well as low-throughput ex vivo methods in which specific cells are isolated for downstream molecular analyses.However,these methods are limited in either the number and type of molecular species they can identify or the number of cells that can be analyzed.High-throughput methods are needed for comprehensive profiling of many cells(>1000)to detect rare cell types,discriminate relevant biomarkers from intrinsic population noise,and reduce the time and cost of measurement.Many established,highthroughput single-cell analyses are not directly applicable because they require tissue dissociation,leading to a loss of spatial information3.No current methods exist that can seamlessly connect spatial mapping to single-cell techniques.In this Perspective,we review current methods for spatially resolved single-cell analysis and discuss the prospect of novel multiplexed imaging probes,called laser particles,which allow individual cells to be tagged in tissue and analyzed subsequently using high-throughput,comprehensive single-cell techniques.