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 *
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 β-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.
We developed a highly efficient method for patterning cells by a novel and simple technique called lift-off cell lithography (LCL). Our approach borrows the key concept of lift-off lithography from microfabrication and utilizes a fully biocompatible process to achieve high-throughput, high-efficiency cell patterning with nearly zero background defects across a large surface area. Using LCL, we reproducibly achieved >70% patterning efficiency for both adherent and non-adherent cells with <1% defects in undesired areas.
This manuscript demonstrates a near-field acoustic platform to synthesize high resolution, complex and non-periodic energy potential wells for patterning micro-objects.
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