Acoustofluidic-based therapeutic apheresis system.

Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the testing of animal model advancements. This limitation restricts our ability to provide treatment options for particularly susceptible infants and children with limited therapeutic alternatives. Here, we report our solution to these challenges through an acoustofluidic-based therapeutic apheresis system designed for processing small blood volumes. Our design integrates an acoustofluidic device with a fluidic stabilizer array on a chip, separating blood components from minimal extracorporeal volumes. We carried out plasma apheresis in mouse models, each with a blood volume of just 280 µL. Additionally, we achieved successful plasmapheresis in a sensitized mouse, significantly lowering preformed donor-specific antibodies and enabling desensitization in a transplantation model. Our system offers a new solution for small-sized subjects, filling a critical gap in existing technologies and providing potential benefits for a wide range of patients.

An acoustofluidic device for the automated separation of platelet-reduced plasma from whole blood.

Separating plasma from whole blood is an important sample processing technique required for fundamental biomedical research, medical diagnostics, and therapeutic applications. Traditional protocols for plasma isolation require multiple centrifugation steps or multiunit microfluidic processing to sequentially remove large red blood cells (RBCs) and white blood cells (WBCs), followed by the removal of small platelets. Here, we present an acoustofluidic platform capable of efficiently removing RBCs, WBCs, and platelets from whole blood in a single step. By leveraging differences in the acoustic impedances of fluids, our device generates significantly greater forces on suspended particles than conventional microfluidic approaches, enabling the removal of both large blood cells and smaller platelets in a single unit. As a result, undiluted human whole blood can be processed by our device to remove both blood cells and platelets (>90%) at low voltages (25 Vpp). The ability to successfully remove blood cells and platelets from plasma without altering the properties of the proteins and antibodies present creates numerous potential applications for our platform in biomedical research, as well as plasma-based diagnostics and therapeutics. Furthermore, the microfluidic nature of our device offers advantages such as portability, cost efficiency, and the ability to process small-volume samples.

Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs.

While mesenchymal stem cells (MSCs) have gained enormous attention due to their unique properties of self-renewal, colony formation, and differentiation potential, the MSC secretome has become attractive due to its roles in immunomodulation, anti-inflammatory activity, angiogenesis, and anti-apoptosis. However, the precise stimulation and efficient production of the MSC secretome for therapeutic applications are challenging problems to solve. Here, we report on Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs: AIMS. We create an acoustofluidic mechanobiological environment to form reproducible three-dimensional MSC aggregates, which produce the MSC secretome with high efficiency. We confirm the increased MSC secretome is due to improved cell-cell interactions using AIMS: the key mediator N-cadherin was up-regulated while functional blocking of N-cadherin resulted in no enhancement of the secretome. After being primed by IFN-γ, the secretome profile of the MSC aggregates contains more anti-inflammatory cytokines and can be used to inhibit the pro-inflammatory response of M1 phenotype macrophages, suppress T cell activation, and support B cell functions. As such, the MSC secretome can be modified for personalized secretome-based therapies. AIMS acts as a powerful tool for improving the MSC secretome and precisely tuning the secretory profile to develop new treatments in translational medicine.

Anticancer-active 3,4-diarylthiolated maleimides synthesis via three-component radical diarylthiolation.

Herein, we report an efficient and simple copper-catalyzed oxidative diarylthiolation of maleimides with sulfur powder and aryl boronic acids, in which S powder was used as a substrate and internal oxidant. The corresponding double C-S bonds coupling products were obtained in moderate to high yields under a simple catalytic system. Mechanistic studies indicated that copper-catalyzed radical thiolation of aryl boronic acids with S powder, and the resulting arylthiyl underwent radical addition with double bonds of maleimides.

A solution to the biophysical fractionation of extracellular vesicles: Acoustic Nanoscale Separation via Wave-pillar Excitation Resonance (ANSWER).

High-precision isolation of small extracellular vesicles (sEVs) from biofluids is essential toward developing next-generation liquid biopsies and regenerative therapies. However, current methods of sEV separation require specialized equipment and time-consuming protocols and have difficulties producing highly pure subpopulations of sEVs. Here, we present Acoustic Nanoscale Separation via Wave-pillar Excitation Resonance (ANSWER), which allows single-step, rapid (<10 min), high-purity (>96% small exosomes, >80% exomeres) fractionation of sEV subpopulations from biofluids without the need for any sample preprocessing. Particles are iteratively deflected in a size-selective manner via an excitation resonance. This previously unidentified phenomenon generates patterns of virtual, tunable, pillar-like acoustic field in a fluid using surface acoustic waves. Highly precise sEV fractionation without the need for sample preprocessing or complex nanofabrication methods has been demonstrated using ANSWER, showing potential as a powerful tool that will enable more in-depth studies into the complexity, heterogeneity, and functionality of sEV subpopulations.

Correction: On-chip stool liquefaction via acoustofluidics.

Correction for 'On-chip stool liquefaction via acoustofluidics' by Shuaiguo Zhao et al., Lab Chip, 2019, 19, 941-947, DOI: .

On-chip stool liquefaction via acoustofluidics.

Microfluidic-based portable devices for stool analysis are important for detecting established biomarkers for gastrointestinal disorders and understanding the relationship between gut microbiota imbalances and various health conditions, ranging from digestive disorders to neurodegenerative diseases. However, the challenge of processing stool samples in microfluidic devices hinders the development of a standalone platform. Here, we present the first microfluidic chip that can liquefy stool samples via acoustic streaming. With an acoustic transducer actively generating strong micro-vortex streaming, stool samples and buffers in microchannel can be homogenized at a flow rate up to 30 µL min-1. After homogenization, an array of 100 µm wide micropillars can further purify stool samples by filtering out large debris. A favorable biocompatibility was also demonstrated for our acoustofluidic-based stool liquefaction chip by examining bacteria morphology and viability. Moreover, stool samples with different consistencies were liquefied. Our acoustofluidic chip offers a miniaturized, robust, and biocompatible solution for stool sample preparation in a microfluidic environment and can be potentially integrated with stool analysis units for designing portable stool diagnostics platforms.