Pixel-based open-space microfluidics for versatile surface processing.

An increasing number of applications in biology, chemistry, and material sciences require fluid manipulation beyond what is possible with current automated pipette handlers, such as gradient generation, interface reactions, reagent streaming, and reconfigurability. In this article, we introduce the pixelated chemical display (PCD), a scalable strategy for highly parallel, reconfigurable liquid handling on open surfaces. Microfluidic "pixels" are created when a fluid stream injected above a surface is confined by neighboring identical fluid streams, forming a repeatable flow unit that can be used to tesselate a surface. PCDs generating up to 144 pixels are fabricated and used to project "chemical moving pictures" made of several reagents over both immersed and dry surfaces, without any physical barrier or wall. This work distinguishes itself from previous work in open-space microfluidics by presenting a device architecture where the number of confinement areas can be scaled to any size. Furthermore, it challenges the open-space tenet that the aspiration rate must be higher than the injection rate for reagents to be confined. Overall, this article sets the foundation for massively parallel surface processing using continuous flow streams and showcases possibilities in both wet and dry surface patterning and roll-to-roll processes.

Programmed coherent coupling in a synthetic DNA-based excitonic circuit.

Natural light-harvesting systems spatially organize densely packed chromophore aggregates using rigid protein scaffolds to achieve highly efficient, directed energy transfer. Here, we report a synthetic strategy using rigid DNA scaffolds to similarly program the spatial organization of densely packed, discrete clusters of cyanine dye aggregates with tunable absorption spectra and strongly coupled exciton dynamics present in natural light-harvesting systems. We first characterize the range of dye-aggregate sizes that can be templated spatially by A-tracts of B-form DNA while retaining coherent energy transfer. We then use structure-based modelling and quantum dynamics to guide the rational design of higher-order synthetic circuits consisting of multiple discrete dye aggregates within a DX-tile. These programmed circuits exhibit excitonic transport properties with prominent circular dichroism, superradiance, and fast delocalized exciton transfer, consistent with our quantum dynamics predictions. This bottom-up strategy offers a versatile approach to the rational design of strongly coupled excitonic circuits using spatially organized dye aggregates for use in coherent nanoscale energy transport, artificial light-harvesting, and nanophotonics.

Rational Design of Plasmonic Nanoparticles for Enhanced Cavitation and Cell Perforation.

Metallic nanoparticles are routinely used as nanoscale antenna capable of absorbing and converting photon energy with subwavelength resolution. Many applications, notably in nanomedicine and nanobiotechnology, benefit from the enhanced optical properties of these materials, which can be exploited to image, damage, or destroy targeted cells and subcellular structures with unprecedented precision. Modern inorganic chemistry enables the synthesis of a large library of nanoparticles with an increasing variety of shapes, composition, and optical characteristic. However, identifying and tailoring nanoparticles morphology to specific applications remains challenging and limits the development of efficient nanoplasmonic technologies. In this work, we report a strategy for the rational design of gold plasmonic nanoshells (AuNS) for the efficient ultrafast laser-based nanoscale bubble generation and cell membrane perforation, which constitute one of the most crucial challenges toward the development of effective gene therapy treatments. We design an in silico rational design framework that we use to tune AuNS morphology to simultaneously optimize for the reduction of the cavitation threshold while preserving the particle structural integrity. Our optimization procedure yields optimal AuNS that are slightly detuned compared to their plasmonic resonance conditions with an optical breakdown threshold 30% lower than randomly selected AuNS and 13% lower compared to similarly optimized gold nanoparticles (AuNP). This design strategy is validated using time-resolved bubble spectroscopy, shadowgraphy imaging and electron microscopy that confirm the particle structural integrity and a reduction of 51% of the cavitation threshold relative to optimal AuNP. Rationally designed AuNS are finally used to perforate cancer cells with an efficiency of 61%, using 33% less energy compared to AuNP, which demonstrate that our rational design framework is readily transferable to a cell environment. The methodology developed here thus provides a general strategy for the systematic design of nanoparticles for nanomedical applications and should be broadly applicable to bioimaging and cell nanosurgery.

Structure-based model for light-harvesting properties of nucleic acid nanostructures.

Programmed self-assembly of DNA enables the rational design of megadalton-scale macromolecular assemblies with sub-nanometer scale precision. These assemblies can be programmed to serve as structural scaffolds for secondary chromophore molecules with light-harvesting properties. Like in natural systems, the local and global spatial organization of these synthetic scaffolded chromophore systems plays a crucial role in their emergent excitonic and optical properties. Previously, we introduced a computational model to predict the large-scale 3D solution structure and flexibility of nucleic acid nanostructures programmed using the principle of scaffolded DNA origami. Here, we use Förster resonance energy transfer theory to simulate the temporal dynamics of dye excitation and energy transfer accounting both for overall DNA nanostructure architecture as well as atomic-level DNA and dye chemical structure and composition. Results are used to calculate emergent optical properties including effective absorption cross-section, absorption and emission spectra and total power transferred to a biomimetic reaction center in an existing seven-helix double stranded DNA-based antenna. This structure-based computational framework enables the efficient in silico evaluation of nucleic acid nanostructures for diverse light-harvesting and photonic applications.

Mechanisms of plasmon-enhanced femtosecond laser nanoablation of silicon.

We perform plasmon-enhanced femtosecond laser ablation of silicon using gold nanorods to produce sub-diffraction limit features. While the observed hole shape seems inconsistent with calculated field distribution, we show that using a carrier diffusion-based model, both shape and depth of the nanoholes can be reliably explained. The laser energy is first deposited into electron-hole pairs that are created in the nanostructure's enhanced near-field. Those carriers then diffuse and transfer their energy to the silicon lattice, producing ablation. Increased importance of the carrier diffusion process is shown to arise from the extreme localization of the deposited energy around the nanostructure, due to the plasmonic effect. The characteristic shape of holes is revealed as a striking signature of the screened charge carriers-phonon coupling that is shown to channel the heat transfer to the lattice and control ablation.

Coherently-enabled environmental control of optics and energy transfer pathways of hybrid quantum dot-metallic nanoparticle systems.

It is well-known that optical properties of semiconductor quantum dots can be controlled using optical cavities or near fields of localized surface plasmon resonances (LSPRs) of metallic nanoparticles. In this paper we study the optics, energy transfer pathways, and exciton states of quantum dots when they are influenced by the near fields associated with plasmonic meta-resonances. Such resonances are formed via coherent coupling of excitons and LSPRs when the quantum dots are close to metallic nanorods and driven by a laser beam. Our results suggest an unprecedented sensitivity to the refractive index of the environment, causing significant spectral changes in the Förster resonance energy transfer from the quantum dots to the nanorods and in exciton transition energies. We demonstrate that when a quantum dot-metallic nanorod system is close to its plasmonic meta-resonance, we can adjust the refractive index to: (i) control the frequency range where the energy transfer from the quantum dot to the metallic nanorod is inhibited, (ii) manipulate the exciton transition energy shift of the quantum dot, and (iii) disengage the quantum dot from the metallic nanoparticle and laser field. Our results show that near meta-resonances the spectral forms of energy transfer and exciton energy shifts are strongly correlated to each other.

Quantum dot-metallic nanorod sensors via exciton-plasmon interaction.

We investigate quantum nanosensors based on hybrid systems consisting of semiconductor quantum dots and metallic nanorods in the near-infrared regime. These sensors can detect biological and chemical substances based on their impact on the coherent exciton-plasmon coupling and molecular resonances supported by such systems when they interact with a laser field. We demonstrate that the ultrahigh sensitivity of such molecular resonances on environmental conditions allows dramatic and nearly instantaneous changes in the total field experienced by the semiconductor quantum dot via minuscule variations of the local refractive indices of the quantum dot or nanorod. The proposed nanosensors can utilize quantum effects to control the sense (or direction) of the changes in the quantum dot emission, allowing us to have bistable switching from dark to bright states or vice versa via adsorption (or detachment) of biomolecules. These sensors can also offer detection of ultra-small variations in the local dielectric constant of the quantum dots or metallic nanorods via coherent induction of time delays in the effective field experienced by the quantum dots when the hybrid systems interact with time-dependent laser fields. This leads to unprecedented bulk refractive index sensitivities. Our results show that one can utilize quantum phase to control the coherent exciton-plasmon dynamics in these sensors such that introduction of a biomolecule can increase or decrease the time delay. These results offer novel ways to detect single biomolecules via application of quantum coherence to convert their impact into spectacular optical events.

Plasma mediated off-resonance plasmonic enhanced ultrafast laser-induced nanocavitation.

The generation of nanobubbles around plasmonic nanostructures is an efficient approach for imaging and therapy, especially in the field of cancer research. We show a novel method using infrared femtosecond laser that generates ≈800 nm bubbles around off-resonance gold nanospheres using 200 mJ/cm(2) 45 fs pulses. We present experimental and theoretical work that demonstrate that the nanobubble formation results from the generation of a nanoscale plasma around the particle due to the enhanced near-field rather than from the heating of the particle. Energy absorbed in the nanoplasma is indeed more than 11 times the energy absorbed in the particle. When compared to the usual approach that uses nanosecond laser to induce the extreme heating of in-resonance nanoparticles to initiate bubble formation, our off-resonance femtosecond technique is shown to bring many advantages, including avoiding the particles fragmentation, working in the optical window of biological material and using the deposited energy more efficiently.

The 2D microfluidics cookbook - modeling convection and diffusion in plane flow devices.

A growing number of microfluidic systems operate not through networks of microchannels but instead through using 2D flow fields. While the design rules for channel networks are already well-known and exposed in microfluidics textbooks, the knowledge underlying transport in 2D microfluidics remains scattered piecemeal and is not easily accessible to experimentalists and engineers. In this tutorial review, we formulate a unified framework for understanding, analyzing and designing 2D microfluidic technologies. We first show how a large number of seemingly different devices can all be modelled using the same concepts, namely flow and diffusion in a Hele-Shaw cell. We then expose a handful of mathematical tools, accessible to any engineer with undergraduate level mathematics knowledge, namely potential flow, superposition of charges, conformal transforms and basic convection-diffusion. We show how these tools can be combined to obtain a simple "recipe" that models almost any imaginable 2D microfluidic system. We end by pointing to more advanced topics beyond 2D microfluidics, namely interface problems and flow and diffusion in the third dimension. This forms the basis of a complete theory allowing for the design and operation of new microfluidic systems.

Microfluidic multipoles theory and applications.

Microfluidic multipoles (MFMs) have been realized experimentally and hold promise for "open-space" biological and chemical surface processing. Whereas convective flow can readily be predicted using hydraulic-electrical analogies, the design of advanced microfluidic multipole is constrained by the lack of simple, accurate models to predict mass transport within them. In this work, we introduce the complete solutions to mass transport in multipolar microfluidics based on the iterative conformal mapping of 2D advection-diffusion around a simple edge into dipoles and multipolar geometries, revealing a rich landscape of transport modes. The models are validated experimentally with a library of 3D printed devices and found in excellent agreement. Following a theory-guided design approach, we further ideate and fabricate two classes of spatiotemporally reconfigurable multipolar devices that are used for processing surfaces with time-varying reagent streams, and to realize a multistep automated immunoassay. Overall, the results set the foundations for exploring, developing, and applying open-space microfluidic multipoles.

Multiscale modeling of plasmonic enhanced energy transfer and cavitation around laser-excited nanoparticles.

Nanoscale bubbles generated around laser-excited metallic nanoparticles are promising candidates for targeted drug and gene delivery in living cells. The development of new nanomaterials for efficient nanobubble-based therapy is however limited by the lack of reliable computational approaches for the prediction of their size and dynamics, due to the wide range of time and space scales involved. In this work, we present a multiscale modeling framework that segregates the various channels of plasmon de-excitation and energy transfer to describe the generation and dynamics of plasmonic nanobubbles. Detailed comparison with time-resolved shadowgraph imaging and spectroscopy data demonstrates that the bubble size, dynamics, and formation threshold can be quantitatively predicted for various types of nanostructures and irradiation parameters, with an error smaller than the experimental uncertainty. Our model in addition provides crucial physical insights into non-linear interactions in the near-field that should guide the experimental design of nanoplasmonic materials for nanobubble-based applications in nanomedicine.

Photon-induced generation and spatial control of extreme pressure at the nanoscale with a gold bowtie nano-antenna platform.

Precise spatial and temporal control of pressure stimulation at the nanometer scale is essential for the fabrication and manipulation of nano-objects, and for exploring single-molecule behaviour of matter under extreme conditions. However, state-of-the-art nano-mechanical transducers require sophisticated driving hardware and are currently limited to moderate pressure regimes. Here we report a gold plasmonic bowtie (AuBT) nano-antennas array that can generate extreme pressure stimulus of ∼100 GPa in the ps (10-12 s) time scale with sub-wavelength resolution upon irradiation with ultra-short laser pulses. Our method leverages the non-linear interaction of photons with water molecules to excite a nano-plasma in the plasmon-enhanced near-field and induce extreme thermodynamic states. The proposed method utilizes laser pulses, which in contrast to micro- and nano-mechanical actuators offers simplicity and versatility. We present time-resolved shadowgraphic imaging, electron microscopy and simulation data that suggest that our platform can efficiently create cavitation nano-bubbles and generate intense pressure in specific patterns, which can be controlled by the selective excitation of plasmon modes of distinct polarizations. This novel platform should enable probing non-invasively the mechanical response of cells and single-molecules at time and pressure regimes that are currently difficult to reach with other methods.

Casting inorganic structures with DNA molds.

We report a general strategy for designing and synthesizing inorganic nanostructures with arbitrarily prescribed three-dimensional shapes. Computationally designed DNA strands self-assemble into a stiff "nanomold" that contains a user-specified three-dimensional cavity and encloses a nucleating gold "seed." Under mild conditions, this seed grows into a larger cast structure that fills and thus replicates the cavity. We synthesized a variety of nanoparticles with 3-nanometer resolution: three distinct silver cuboids with three independently tunable dimensions, silver and gold nanoparticles with diverse cross sections, and composite structures with homo- and heterogeneous components. The designer equilateral silver triangular and spherical nanoparticles exhibited plasmonic properties consistent with electromagnetism-based simulations. Our framework is generalizable to more complex geometries and diverse inorganic materials, offering a range of applications in biosensing, photonics, and nanoelectronics.

Visible and near infrared resonance plasmonic enhanced nanosecond laser optoporation of cancer cells.

In this paper, we report a light driven, non-invasive cell membrane perforation technique based on the localized field amplification by a nanosecond pulsed laser near gold nanoparticles (AuNPs). The optoporation phenomena is investigated with pulses generated by a Nd:YAG laser for two wavelengths that are either in the visible (532 nm) or near infrared (NIR) (1064 nm). Here, the main objective is to compare on and off localized surface plasmonic resonance (LSPR) to introduce foreign material through the cell membrane using nanosecond laser pulses. The membrane permeability of human melanoma cells (MW278) has been successfully increased as shown by the intake of a fluorescent dye upon irradiation. The viability of this laser driven perforation method is evaluated by propidium iodide exclusion as well as MTT assay. Our results show that up to 25% of the cells are perforated with 532 nm pulses at 50 mJ/cm(2) and around 30% of the cells are perforated with 1064 nm pulses at 1 J/cm(2). With 532 nm pulses, the viability 2 h after treatment is 64% but it increases to 88% 72 h later. On the other hand, the irradiation with 1064 nm pulses leads to an improved 2 h viability of 81% and reaches 98% after 72 h. Scanning electron microscopy images show that the 5 pulses delivered during treatment induce changes in the AuNPs size distribution when irradiated by a 532 nm beam, while this distribution is barely affected when 1064 nm is used.

Off-resonance plasmonic enhanced femtosecond laser optoporation and transfection of cancer cells.

A femtosecond laser based transfection method using off-resonance plasmonic gold nanoparticles is described. For human cancer melanoma cells, the treatment leads to a very high perforation rate of 70%, transfection efficiency three times higher than for conventional lipofection, and very low toxicity (<1%). Off-resonance laser excitation inhibited the fracture of the nanoparticles into possibly toxic DNA intercalating particles. This efficient and low toxicity method is a promising alternative to viral transfection for skin cancer treatment.