Quantifying local stiffness and forces in soft biological tissues using droplet optical microcavities.

Mechanical properties of biological tissues fundamentally underlie various biological processes and noncontact, local, and microscopic methods can provide fundamental insights. Here, we present an approach for quantifying the local mechanical properties of biological materials at the microscale, based on measuring the spectral shifts of the optical resonances in droplet microcavities. Specifically, the developed method allows for measurements of deformations in dye-doped oil droplets embedded in soft materials or biological tissues with an error of only 1 nm, which in turn enables measurements of anisotropic stress inside tissues as small as a few pN/µm2. Furthermore, by applying an external strain, Young's modulus can be measured in the range from 1 Pa to 35 kPa, which covers most human soft tissues. Using multiple droplet microcavities, our approach could enable mapping of stiffness and forces in inhomogeneous soft tissues and could also be applied to in vivo and single-cell experiments. The developed method can potentially lead to insights into the mechanics of biological tissues.

Deep tissue localization and sensing using optical microcavity probes.

Optical microcavities and microlasers were recently introduced as probes inside living cells and tissues. Their main advantages are spectrally narrow emission lines and high sensitivity to the environment. Despite numerous novel methods for optical imaging in strongly scattering biological tissues, imaging at single-cell resolution beyond the ballistic light transport regime remains very challenging. Here, we show that optical microcavity probes embedded inside cells enable three-dimensional localization and tracking of individual cells over extended time periods, as well as sensing of their environment, at depths well beyond the light transport length. This is achieved by utilizing unique spectral features of the whispering-gallery modes, which are unaffected by tissue scattering, absorption, and autofluorescence. In addition, microcavities can be functionalized for simultaneous sensing of various parameters, such as temperature or pH value, which extends their versatility beyond the capabilities of standard fluorescent labels.

Optical-resonance-assisted generation of super monodisperse microdroplets and microbeads with nanometer precision.

Droplets with predefined sizes have been controllably produced at the tip of a micro-capillary immersed in an external fluid while tracking the high Q-factor whispering gallery modes (WGM). The modes were fitted to a model to give precise real-time size measurement, which was used as a feedback to control the pressure in the capillary and the release of the droplet from the capillary when it reached the target size. In this way a dispersion of highly monodisperse droplets anywhere in the size range from 5 µm to 50 µm were produced. To fabricate solid beads, the droplets were made from a liquid photopolymer and were later polymerized with UV light. The polymerized beads showed long term stability. The diameter of the generated oil droplets and polymerized microbeads could be reproduced with a standard deviation of 1.1 nm and 20 nm, respectively. Overall, the demonstrated method improves the size precision by three and two orders of magnitude for microdroplets and microbeads, respectively, compared to standard production methods such as reported in microfluidics. Encoding of short words and numbers has been demonstrated by producing three beads with predefined sizes. The stored information has been read from the emitted spectrum.