An implantable multifunctional neural microprobe for simultaneous multi-analyte sensing and chemical delivery.

A multifunctional chemical neural probe fabrication process exploiting PDMS thin-film transfer to incorporate a microfluidic channel onto a silicon-based microelectrode array (MEA) platform, and enzyme microstamping to provide multi-analyte detection is described. The Si/PDMS hybrid chemtrode, modified with a nano-based on-probe IrOx reference electrode, was validated in brain phantoms and in rat brain.

Intracellular Photothermal Delivery for Suspension Cells Using Sharp Nanoscale Tips in Microwells.

Efficient intracellular delivery of biomolecules into cells that grow in suspension is of great interest for biomedical research, such as for applications in cancer immunotherapy. Although tremendous effort has been expended, it remains challenging for existing transfer platforms to deliver materials efficiently into suspension cells. Here, we demonstrate a high-efficiency photothermal delivery approach for suspension cells using sharp nanoscale metal-coated tips positioned at the edge of microwells, which provide controllable membrane disruption for each cell in an array. Self-aligned microfabrication generates a uniform microwell array with three-dimensional nanoscale metallic sharp tip structures. Suspension cells self-position by gravity within each microwell in direct contact with eight sharp tips, where laser-induced cavitation bubbles generate transient pores in the cell membrane to facilitate intracellular delivery of extracellular cargo. A range of cargo sizes were tested on this platform using Ramos suspension B cells with an efficiency of >84% for Calcein green (0.6 kDa) and >45% for FITC-dextran (2000 kDa), with retained viability of >96% and a throughput of >100 000 cells delivered per minute. The bacterial enzyme ß-lactamase (29 kDa) was delivered into Ramos B cells and retained its biological activity, whereas a green fluorescence protein expression plasmid was delivered into Ramos B cells with a transfection efficiency of >58%, and a viability of >89% achieved.

Ionic-surfactant-mediated electro-dewetting for digital microfluidics.

The ability to manipulate droplets on a substrate using electric signals1-known as digital microfluidics-is used in optical2,3, biomedical4,5, thermal6 and electronic7 applications and has led to commercially available liquid lenses8 and diagnostics kits9,10. Such electrical actuation is mainly achieved by electrowetting, with droplets attracted towards and spreading on a conductive substrate in response to an applied voltage. To ensure strong and practical actuation, the substrate is covered with a dielectric layer and a hydrophobic topcoat for electrowetting-on-dielectric (EWOD)11-13; this increases the actuation voltage (to about 100 volts) and can compromise reliability owing to dielectric breakdown14, electric charging15 and biofouling16. Here we demonstrate droplet manipulation that uses electrical signals to induce the liquid to dewet, rather than wet, a hydrophilic conductive substrate without the need for added layers. In this electrodewetting mechanism, which is phenomenologically opposite to electrowetting, the liquid-substrate interaction is not controlled directly by electric field but instead by field-induced attachment and detachment of ionic surfactants to the substrate. We show that this actuation mechanism can perform all the basic fluidic operations of digital microfluidics using water on doped silicon wafers in air, with only ±2.5 volts of driving voltage, a few microamperes of current and about 0.015 times the critical micelle concentration of an ionic surfactant. The system can also handle common buffers and organic solvents, promising a simple and reliable microfluidic platform for a broad range of applications.

Flexible, multifunctional neural probe with liquid metal enabled, ultra-large tunable stiffness for deep-brain chemical sensing and agent delivery.

Flexible neural probes have been pursued previously to minimize the mechanical mismatch between soft neural tissues and implants and thereby improve long-term performance. However, difficulties with insertion of such probes deep into the brain severely restricts their utility. We describe a solution to this problem using gallium (Ga) in probe construction, taking advantage of the solid-to-liquid phase change of the metal at body temperature and probe shape deformation to provide temperature-dependent control of stiffness over 5 orders of magnitude. Probes in the stiff state were successfully inserted 2 cm-deep into agarose gel "brain phantoms" and into rat brains under cooled conditions where, upon Ga melting, they became ultra soft, flexible, and stretchable in all directions. The current 30 µm-thick probes incorporated multilayer, deformable microfluidic channels for chemical agent delivery, electrical interconnects through Ga wires, and high-performance electrochemical glutamate sensing. These PDMS-based microprobes of ultra-large tunable stiffness (ULTS) should serve as an attractive platform for multifunctional chronic neural implants.

Liquid Metal-Based Multifunctional Micropipette for 4D Single Cell Manipulation.

A novel manufacturing approach to fabricate liquid metal-based, multifunctional microcapillary pipettes able to provide electrodes with high electrical conductivity for high-frequency electrical stimulation and measurement is proposed. 4D single cell manipulation is realized by applying multifrequency, multiamplitude, and multiphase electrical signals to the microelectrodes near the pipette tip to create 3D dielectrophoretic trap and 1D electrorotation, simultaneously. Functions such as single cell trapping, patterning, transfer, and rotation are accomplished. Cell viability and multiday proliferation characterization has confirmed the biocompatibility of this approach. This is a simple, low-cost, and fast fabrication process that requires no cleanroom and photolithography step to manufacture 3D microelectrodes and microchannels for easy access to a wide user base for broad applications.

Contact Angle Measurement of Small Capillary Length Liquid in Super-repelled State.

The difficulty of measuring very large contact angles (>150 degrees) has become more relevant with the increased popularity of super-repellent surfaces. Measurement is more difficult for dynamic contact angles, for which theoretical profiles do not fit well, and small capillary length liquids, whose sessile droplets sag by gravity. Here, we expand the issue to the limit by investigating dynamic contact angles of liquids with an extremely small capillary length (<1.0 mm), empowered by the superomniphobic surface that can super-repel even fluorinated solvents, which highly wet all materials. Numerically simulating and experimentally testing 13 different liquids on the superomniphobic surface, we discover their dynamic contact angles can be measured with a consistent accuracy despite their vastly different capillary lengths if one keeps the lens magnification inversely proportional to the capillary length. Verifying the droplet equator height is a key parameter, we propose a new Bond number defined by the equator height and optical resolution to represent the measurement accuracy of large contact angles. Despite negligible improvement for most liquids today, the proposed approach teaches how to measure very large contact angles with consistent accuracy when any of the liquids in consideration has a capillary length below 1.0 mm.

A dynamic Cassie-Baxter model.

Contact-angle hysteresis of a liquid suspended on surface microstructures, namely in a Cassie-Baxter state, is determined mainly by the receding contact line although not fully understood. Existing modified Cassie-Baxter models predict some but not most experimental data in the literature. Noting that most models were based on the two-dimensional (2-D) principle whereas the experiments were under three-dimensional (3-D) conditions, here we develop a 2-D experiment. While 3-D experiments measure the receding contact lines averaged over space and time, 2-D experiments eliminate the spatial averaging and can further eliminate the temporal averaging by high-speed visualization. The resulting details of the contact line motion lead us to propose a 2-D model, which incorporates the contact-line friction. The new 2-D model matches the 2-D experimental results excellently while all existing models show significant deviation. By introducing a line solid fraction term, the 2-D model is further generalized to a 3-D model, which successfully predicts a wide range of 3-D data in the literature regardless of their distinct microstructures and receding modes.

Repellent surfaces. Turning a surface superrepellent even to completely wetting liquids.

Superhydrophobic and superoleophobic surfaces have so far been made by roughening a hydrophobic material. However, no surfaces were able to repel extremely-low-energy liquids such as fluorinated solvents, which completely wet even the most hydrophobic material. We show how roughness alone, if made of a specific doubly reentrant structure that enables very low liquid-solid contact fraction, can render the surface of any material superrepellent. Starting from a completely wettable material (silica), we micro- and nanostructure its surface to make it superomniphobic and bounce off all available liquids, including perfluorohexane. The same superomniphobicity is further confirmed with identical surfaces of a metal and a polymer. Free of any hydrophobic coating, the superomniphobic silica surface also withstands temperatures over 1000°C and resists biofouling.