Parallel droplet microfluidics for high throughput cell encapsulation and synthetic microgel generation

Cells can be microencapsulated in synthetic hydrogel microspheres(microgels)using droplet microfluidics,but microfluidic devices with a single droplet generating geometry have limited throughput,especially as microgel diameter decreases.Here we demonstrate microencapsulation of human mesenchymal stem cells(hMSCs)in small(o100μm diameter)microgels utilizing parallel droplet generators on a two-layer elastomer device,which has 600% increased throughput vs.single-nozzle devices.Distribution of microgel diameters were compared between products of parallel vs.single-nozzle configurations for two square nozzle widths,35 and 100μm.Microgels produced on parallel nozzles were equivalent to those produced on single nozzles,with substantially the same polydispersity.Microencapsulation of hMSCs was compared for parallel nozzle devices of each width.Thirty five micrometer wide nozzle devices could be operated at twice the cell concentration of 100μm wide nozzle devices but produced more empty microgels than predicted by a Poisson distribution.Hundred micrometer wide nozzle devices produced microgels as predicted by a Poisson distribution.Polydispersity of microgels did not increase with the addition of cells for either nozzle width.hMSCs encapsulated on 35μm wide nozzle devices had reduced viability(~70%)and a corresponding decrease in vascular endothelial growth factor(VEGF)secretion compared to hMSCs cultured on tissue culture(TC)plastic.Encapsulating hMSCs using 100μm wide nozzle devices mitigated loss of viability and function,as measured by VEGF secretion.

Fully implantable and battery-free wireless optoelectronic system for modulable cancer therapy and real-time monitoring

Photodynamic therapy(PDT)is attracting attention as a next-generation cancer treatment that can selectively destroy malignant tissues,exhibit fewer side effects,and lack pain during treatments.Implantable PDT systems have recently been developed to resolve the issues of bulky and expensive conventional PDT systems and to implement continuous and repetitive treatment.Existing implantable PDT systems,however,are not able to perform multiple functions simultaneously,such as modulating light intensity,measuring,and transmitting tumor-related data,resulting in the complexity of cancer treatment.Here,we introduce a flexible and fully implantable wireless optoelectronic system capable of continuous and effective cancer treatment by fusing PDT and hyperthermia and enabling tumor size monitoring in real-time.This system exploits micro inorganic light-emitting diodes(μ-LED)that emit light with a wavelength of 624 nm,designed not to affect surrounding normal tissues by utilizing a fully programmable light intensity ofμ-LED and precisely monitoring the tumor size by Si phototransistor during a long-term implantation(2–3 weeks).The superiority of simultaneous cancer treatment and tumor size monitoring capabilities of our system operated by wireless power and data transmissions with a cell phone was confirmed through in vitro experiments,ray-tracing simulation results,and a tumor xenograft mouse model in vivo.This all-in-one single system for cancer treatment offers opportunities to not only enable effective treatment of tumors located deep in the tissue but also enable precise and continuous monitoring of tumor size in real-time.

Soft wearable flexible bioelectronics integrated with an anklefoot exoskeleton for estimation of metabolic costs and physical effort

Activities and physical effort have been commonly estimated using a metabolic rate through indirect calorimetry to capture breath information.The physical effort represents the work hardness used to optimize wearable robotic systems.Thus,personalization and rapid optimization of the effort are critical.Although respirometry is the gold standard for estimating metabolic costs,this method requires a heavy,bulky,and rigid system,limiting the system’s field deployability.Here,this paper reports a soft,flexible bioelectronic system that integrates a wearable ankle-foot exoskeleton,used to estimate metabolic costs and physical effort,demonstrating the potential for real-time wearable robot adjustments based on biofeedback.Data from a set of activities,including walking,running,and squatting with the biopatch and exoskeleton,determines the relationship between metabolic costs and heart rate variability root mean square of successive differences(HRV-RMSSD)(R=−0.758).Collectively,the exoskeleton-integrated wearable system shows potential to develop a field-deployable exoskeleton platform that can measure wireless real-time physiological signals.

Lipid nanoparticles deliver mRNA to the blood-brain barrier

Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous administration.These clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains challenging.Here we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted LNP.These data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous administration.Given the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.