Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations.

Messenger RNA (mRNA) delivery provides gene therapy with the potential to achieve transient therapeutic efficacy without risk of insertional mutagenesis. Amongst other applications, mRNA can be employed as a platform to deliver gene editing molecules, to achieve protein expression as an alternative to enzyme replacement therapies, and to express chimeric antigen receptors (CARs) on immune cells for the treatment of cancer. We designed a novel microfluidic device that allows for efficient mRNA delivery via volume exchange for convective transfection (VECT). In the device, cells flow through a ridged channel that enforces a series of ultra-fast and large intensity deformations able to transiently open pores and induce convective transport of mRNA into the cell. Here, we describe efficient delivery of mRNA into T cells, natural killer (NK) cells and hematopoietic stem and progenitor cells (HSPCs), three human primary cell types widely used for ex vivo gene therapy applications. Results demonstrate that the device can operate at a wide range of cell and payload concentrations and that ultra-fast compressions do not have a negative impact on T cell function, making this a novel and competitive platform for the development of ex vivo mRNA-based gene therapies and other cell products engineered with mRNA.

Printed, Flexible Lactate Sensors: Design Considerations Before Performing On-Body Measurements.

This work reports the process of sensor development, optimization, and characterization before the transition to on-body measurements can be made. Sensors using lactate oxidase as a sensing mechanism and tetrathiafulvalene as a mediator were optimized for sporting applications. Optimized sensors show linear range up to 24 mM lactate and sensitivity of 4.8 µA/mM which normalizes to 68 µA*cm-2/mM when accounting for surface area of the sensor. The optimized sensors were characterized 3 different ways: using commercially available reference and counter electrodes, using printed reference and counter electrodes, and using a printed reference electrode with no counter electrode. Sensors intended for measuring sweat must be selective in the presence of sweat constituents. Thus, in addition to traditional characterization in pH 7.0 buffer, we characterized sensor performance in solutions intended to approximate sweat. Sensor performance in pH 7.0 buffer solution was not reflective of sensor performance in artificial sweat, indicating that further characterization is necessary between sensor measurement in pH 7.0 buffer and on-body measurements. Furthermore, we performed enzyme activity measurements and sensor measurements concurrently in five different salts individually, finding that while NH4Cl and MgCl2 do not affect enzyme activity or sensor performance in physiologically relevant ranges of salt concentration, NaCl concentration or KCl concentration decreases enzyme activity and sensor current. On the other hand, CaCl2 induced a nonlinear change in sensor performance and enzyme activity with increasing salt concentration.

Flexible and stretchable power sources for wearable electronics.

Flexible and stretchable power sources represent a key technology for the realization of wearable electronics. Developing flexible and stretchable batteries with mechanical endurance that is on par with commercial standards and offer compliance while retaining safety remains a significant challenge. We present a unique approach that demonstrates mechanically robust, intrinsically safe silver-zinc batteries. This approach uses current collectors with enhanced mechanical design, such as helical springs and serpentines, as a structural support and backbone for all battery components. We show wire-shaped batteries based on helical band springs that are resilient to fatigue and retain electrochemical performance over 17,000 flexure cycles at a 0.5-cm bending radius. Serpentine-shaped batteries can be stretched with tunable degree and directionality while maintaining their specific capacity. Finally, the batteries are integrated, as a wearable device, with a photovoltaic module that enables recharging of the batteries.