Exosomes, with diameters ranging from 30 to 150 nm, are saucer-shaped extracellular vesicles (EVs) secreted by various type of human cells. They are present in virtually all bodily fluids. Owing to their abundant nucleic acid and protein content, exosomes have emerged as promising biomarkers for noninvasive molecular diagnostics. However, the need for exosome separation purification presents tremendous technical challenges due to their minuscule size. In recent years, microfluidic technology has garnered substantial interest as a promising alternative capable of excellent separation performance, reduced reagent consumption, and lower overall device and operation costs. In this context, we hereby propose a novel microfluidic strategy based on thermally oxidized deterministic lateral displacement (DLD) arrays with tapered shapes to enhance separation performance. We have achieved more than 90% purity in both polystyrene nanoparticle and exosome experiments. The use of thermal oxidation also significantly reduces fabrication complexity by avoiding the use of high-precision lithography. Furthermore, in a simulation model, we attempt to integrate the use of dielectrophoresis (DEP) to overcome the size-based nature of DLD and distinguish particles that are close in size but differ in biochemical compositions (e.g., lipoproteins, exomeres, retroviruses). We believe the proposed strategy heralds a versatile and innovative platform poised to enhance exosome analysis across a spectrum of biochemical applications.

Small extracellular vesicles (sEVs) are extracellular vesicles with diameters ranging from 30 to 150 nm, harboring proteins and nucleic acids that reflect their source cells and act as vital mediators of intercellular communication. The comprehensive analysis of sEVs is hindered by the complex composition of biofluids that contain various extracellular vesicles. Conventional separation methods, such as ultracentrifugation and immunoaffinity capture, face routine challenges in operation complexity, cost, and compromised recovery rates. Microfluidic technologies, particularly viscoelastic microfluidics, offer a promising alternative for sEV separation due to its field-free nature, fast and simple operation procedure, and minimal sample consumption. In this context, we here introduce an innovative viscoelastic approach designed to exploit the viscosity gradient-induced force with size-dependent characteristics, thereby enabling the efficient separation of nano-sized particles and sEVs from larger impurities. We first seek to illustrate the underlying mechanism of the viscosity gradient-induced force, followed by experimental validation with fluorescent nanoparticles demonstrating separation results consistent with qualitative analysis. We believe that this work is the first to report such viscosity gradient-induced phenomenon in the microfluidic context. The presented approach achieves ∼80% for both target purity and recovery rate. We further demonstrate effective sEV separation using our device to showcase its efficacy in the real biological context, highlighting its potential as a versatile, label-free platform for sEV analysis in both fundamental biological research and clinical applications.

Here we present a novel strategy for DNA data random access by combining droplet digital polymerase chain reaction (ddPCR) with on-chip fluorescence-based sorting. Standard PCR technique has been widely used for random access in DNA data storage, i.e., using specific primer sequences as file indexes. However, such amplification carried out in bulk solutions suffers from issues in both sensitivity (for retrieving rare data) and selectivity (for file accessing accuracy) [1]. In this work, ddPCR was implemented during data accessing process to replace bulk amplification and DNA sequences encoding different files were separated into droplet partitions. After amplification, those positive droplets containing sequences corresponding to the requested files are then sorted on-chip using dielectrophoresis. Once these droplets are collected, the target file can be retrieved through Next-Generation Sequencing (NGS) and data decoding. Our strategy is anticipated to significantly enhance the selectivity and sensitivity of DNA data storage retrieval while mitigating the adverse effects associated with bulk amplification.

Using DNA as the next-generation medium for data storage offers unparalleled advantages in terms of data density, storage duration, and power consumption as compared to existing data storage technologies. To meet the high-speed data writing requirements in DNA data storage, this paper proposes a novel design for an ultra-high-density and high-throughput DNA synthesis platform. The presented design mainly leverages two functional modules: a dynamic random-access memory (DRAM)-like integrated circuit (IC) responsible for electrode addressing and voltage supply, and the static droplet array (SDA)-based microfluidic structure to eliminate any reaction species diffusion concern in electrochemical DNA synthesis. Through theoretical analysis and simulation studies, we validate the effective addressing of 10 million electrodes and stable, adjustable voltage supply by the integrated circuit. We also demonstrate a reaction unit size down to 3.16 × 3.16 μm², equivalent to 10 million/cm², that can rapidly and stably generate static droplets at each site, effectively constraining proton diffusion. Finally, we conducted a synthesis cycle experiment by incorporating fluorescent beacons on a microfabricated electrode array to examine the feasibility of our design.

This paper proposes a novel microfluidic device based on the synergy of deterministic lateral displacement (DLD) and dielectrophoresis (DEP) techniques, which enables the differentiation of exosomes from both large extracellular vesicles (e.g. apoptotic vesicles, ectosomes) and particles that are close in size but differ in biochemical compositions (e.g. Lipoproteins, Exomeres, Retroviruses). We fabricated nanoscale pillar arrays through $\gt1 ~\mu$m resolution photolithography by making innovative use of thermal oxidation, which significantly reduces fabrication costs by avoiding the use of high-precision lithography. We further proceeded to optimize device design with simulation study and conduct experimental verification.

This paper proposes a novel DNA synthesis chip design targeting data storage application, achieving ultrahigh throughput(10 ⁷ ) and unit density(10 ⁷ /cm ² ) via the synergetic function of a dynamic random access memory (DRAM)-like integrated circuit (IC) and microfluidic confinement architecture. Through theoretical and simulation study, we verify individual addressability to 10 ⁷ synthesis units by maintaining stable voltage output. We also demonstrate effective proton confinement through microfluidic structures at 10 ⁷ /cm ² unit density.