Wireless dielectrophoresis trapping and remote impedance sensing via resonant wireless power transfer.

Nearly all biosensing platforms can be described using two fundamental steps-collection and detection. Target analytes must be delivered to a sensing element, which can then relay the transduced signal. For point-of-care technologies, where operation is to be kept simple, typically the collection step is passive diffusion driven-which can be slow or limiting under low concentrations. This work demonstrates an integration of both active collection and detection by using resonant wireless power transfer coupled to a nanogap capacitor. Nanoparticles suspended in deionized water are actively trapped using wireless dielectrophoresis and positioned within the most sensitive fringe field regions for wireless impedance-based detection. Trapping of 40 nm particles and larger is demonstrated using a 3.5 VRMS, 1 MHz radiofrequency signal delivered over a distance greater than 8 cm from the nanogap capacitor. Wireless trapping and release of 1 µm polystyrene beads is simultaneously detected in real-time over a distance of 2.5 cm from the nanogap capacitor. Herein, geometric scaling strategies coupled with optimal circuit design is presented to motivate combined collection and detection biosensing platforms amenable to wireless and/or smartphone operation.

Open-channel microfluidics via resonant wireless power transfer.

Open-channel microfluidics enables precise positioning and confinement of liquid volume to interface with tightly integrated optics, sensors, and circuit elements. Active actuation via electric fields can offer a reduced footprint compared to passive microfluidic ensembles and removes the burden of intricate mechanical assembly of enclosed systems. Typical systems actuate via manipulating surface wettability (i.e., electrowetting), which can render low-voltage but forfeits open-microchannel confinement. The dielectric polarization force is an alternative which can generate open liquid microchannels (sub-100 µm) but requires large operating voltages (50-200 VRMS) and low conductivity solutions. Here we show actuation of microchannels as narrow as 1 µm using voltages as low as 0.5 VRMS for both deionized water and physiological buffer. This was achieved using resonant, nanoscale focusing of radio frequency power and an electrode geometry designed to abate surface tension. We demonstrate practical fluidic applications including open mixing, lateral-flow protein labeling, filtration, and viral transport for infrared biosensing-known to suffer strong absorption losses from enclosed channel material and water. This tube-free system is coupled with resonant wireless power transfer to remove all obstructing hardware - ideal for high-numerical-aperture microscopy. Wireless, smartphone-driven fluidics is presented to fully showcase the practical application of this technology.

Nano-Optical Tweezers: Methods and Applications for Trapping Single Molecules and Nanoparticles.

The front cover artwork is provided by Prof. Sang-Hyun Oh's group at the University of Minnesota. The image shows the optical trapping of chiral nanoparticles using coaxial nano-optical tweezers, devices capable of harnessing light to manipulate objects a few nanometers in size. Read the full text of the Review at 10.1002/cphc.202100004.

Nano-Optical Tweezers: Methods and Applications for Trapping Single Molecules and Nanoparticles.

Optical tweezers were developed in 1970 by Arthur Ashkin as a tool for the manipulation of micron-sized particles. Ashkin's original design was then adapted for a variety of purposes, such as trapping and manipulation of biological materials[1] and the laser cooling of atoms.[2,3] More recent development has led to nano-optical tweezers, for trapping particles on the scale of only a few nanometers, and holographic tweezers, which allow for dynamic control of multiple traps in real-time. These alternatives to conventional optical tweezers have made it possible to trap single molecules and to perform a variety of studies on them. Presented here is a review of recent developments in nano-optical tweezers and their current and future applications.

Precisely calibrated and spatially informed illumination for conventional fluorescence and improved PALM imaging applications.

Spatial light modulation using cost efficient digital micromirror devices (DMD) is finding broad applications in fluorescence microscopy due to the reduction of phototoxicity and bleaching and the ability to manipulate proteins in optogenetic experiments. However, precise illumination by DMDs and their application to single-molecule localization microscopy (SMLM) remained a challenge because of non-linear distortions between the DMD and camera coordinate systems caused by optical components in the excitation and emission path. Here we develop a fast and easy to implement calibration procedure that determines these distortions and matches the DMD and camera coordinate system with a precision below the optical diffraction limit. As a result, a region from a fluorescence image can be selected with a higher precision for illumination compared to a rigid transformation allowed by manual alignment of the DMD. We first demonstrate the application of our precisely calibrated light modulation by performing a proof of concept fluorescence recovery after photobleaching experiment with the endoplasmic reticulum-localized protein IRE1 fused to GFP in budding yeast (S. cerevisiae). Next, we develop a spatially informed photoactivation approach for SMLM in which only regions of the cell that contain photoactivatable fluorescent proteins are selected for photoactivation. The reduced exposure of the cells to 405 nm light increased the possible imaging time by 44% until phototoxic effects cause a dominant fluorescence background and a change in cell morphology. As a result, the mean number of reliable single-molecule localizations was also significantly increased by 28%. Since the localization precision and the ability for single-molecule tracking is not altered compared to traditional photoactivation of the entire field of view, spatially informed photoactivation significantly improves the quality of SMLM images and single-molecule tracking data. Our precise calibration method therefore lays the foundation for improved SMLM with active feedback photoactivation far beyond the applications in this work.

Plasmonic Sensing on Symmetric Nanohole Arrays Supporting High-Q Hybrid Modes and Reflection Geometry.

Refractometric sensors utilizing surface plasmon resonance (SPR) should satisfy a series of performance metrics, bulk sensitivity, thin-film sensitivity, refractive-index resolution, and high-Q-factor resonance, as well as practical requirements such as manufacturability and the ability to separate optical and fluidic paths via reflection-mode sensing. While many geometries such as nanohole, nanoslit, and nanoparticles have been employed, it is nontrivial to engineer nanostructures to satisfy all of the aforementioned requirements. We combine gold nanohole arrays with a water-index-matched Cytop film to demonstrate reflection-mode, high-Q-factor (Qexp = 143) symmetric plasmonic sensor architecture. Using template stripping with a Cytop film, we can replicate a large number of index-symmetric nanohole arrays, which support sharp plasmonic resonances that can be probed by light reflected from their backside with a high extinction amplitude. The reflection geometry separates the optical and microfluidic paths without sacrificing sensor performance as is the case of standard (index-asymmetric) nanohole arrays. Furthermore, plasmon hybridization caused by the array refractive-index symmetry enables dual-mode detection that allows distinction of refractive-index changes occurring at different distances from the surface, making it possible to identify SPR response from differently sized particles or to distinguish binding events near the surface from bulk index changes. Due to the unique combination of a dual-mode reflection-configuration sensing, high-Q plasmonic modes, and template-stripping nanofabrication, this platform can extend the utility of nanohole SPR for sensing applications involving biomolecules, polymers, nanovesicles, and biomembranes.

Integrated Nanogap Platform for Sub-Volt Dielectrophoretic Trapping and Real-Time Raman Imaging of Biological Nanoparticles.

A rapid, label-free, and broadly applicable chemical analysis platform for nanovesicles and subcellular components is highly desirable for diagnostic assays. We demonstrate an integrated nanogap plasmonic sensing platform that combines subvolt dielectrophoresis (DEP) trapping, gold nanoparticles (AuNPs), and a lineated illumination scheme for real-time, surface-enhanced Raman spectroscopy (SERS) imaging of biological nanoparticles. Our system is capable of isolating suspended sub-100 nm vesicles and imaging the Raman spectra of their cargo within seconds, 100 times faster than conventional point-scan Raman systems. Bare AuNPs are spiked into solution and simultaneously trapped with the nanovesicles along the gap to boost local optical fields. In addition, our platform offers simultaneous and delay-free spatial and temporal multiplexing functionality. These nanogap devices can be mass-produced via atomic layer lithography and provide a practical platform for high-speed SERS analysis of biological nanoparticles.

Surface Plasmon Resonance Study of the Binding of PEO-PPO-PEO Triblock Copolymer and PEO Homopolymer to Supported Lipid Bilayers.

Poloxamer 188 (P188), a poly(ethylene oxide)- b-poly(propylene oxide)- b-poly(ethylene oxide) triblock copolymer, protects cell membranes against various external stresses, whereas poly(ethylene oxide) (PEO; 8600 g/mol) homopolymer lacks protection efficacy. As part of a comprehensive effort to elucidate the protection mechanism, we used surface plasmon resonance (SPR) to obtain direct evidence of binding of the polymers onto supported lipid bilayers. Binding kinetics and coverage of P188 and PEO were examined and compared. Most notably, PEO exhibited membrane association comparable to that of P188, evidenced by comparable association rate constants and coverage. This result highlights the need for additional mechanistic understanding beyond simple membrane association to explain the differential efficacy of P188 in therapeutic applications.

Low-Power Optical Trapping of Nanoparticles and Proteins with Resonant Coaxial Nanoaperture Using 10 nm Gap.

We present optical trapping with a 10 nm gap resonant coaxial nanoaperture in a gold film. Large arrays of 600 resonant plasmonic coaxial nanoaperture traps are produced on a single chip via atomic layer lithography with each aperture tuned to match a 785 nm laser source. We show that these single coaxial apertures can act as efficient nanotweezers with a sharp potential well, capable of trapping 30 nm polystyrene nanoparticles and streptavidin molecules with a laser power as low as 4.7 mW. Furthermore, the resonant coaxial nanoaperture enables real-time label-free detection of the trapping events via simple transmission measurements. Our fabrication technique is scalable and reproducible, since the critical nanogap dimension is defined by atomic layer deposition. Thus our platform shows significant potential to push the limit of optical trapping technologies.

Dynamic placement of plasmonic hotspots for super-resolution surface-enhanced Raman scattering.

In this paper, we demonstrate dynamic placement of locally enhanced plasmonic fields using holographic laser illumination of a silver nanohole array. To visualize these focused "hotspots", the silver surface was coated with various biological samples for surface-enhanced Raman spectroscopy (SERS) imaging. Due to the large field enhancements, blinking behavior of the SERS hotspots was observed and processed using a stochastic optical reconstruction microscopy algorithm enabling super-resolution localization of the hotspots to within 10 nm. These hotspots were then shifted across the surface in subwavelength (<100 nm for a wavelength of 660 nm) steps using holographic illumination from a spatial light modulator. This created a dynamic imaging and sensing surface, whereas static illumination would only have produced stationary hotspots. Using this technique, we also show that such subwavelength shifting and localization of plasmonic hotspots has potential for imaging applications. Interestingly, illuminating the surface with randomly shifting SERS hotspots was sufficient to completely fill in a wide field of view for super-resolution chemical imaging.