Dinh-Tuan Phan

To perform precision medicine in real-time at home, a device capable of long-distance continuously monitoring target biomolecules in unprocessed blood under dynamic situations is essential. In this study, an integrative buffer-free wireless device is developed to measure drug concentrations in patient’s blood in real time for remote clinical healthcare. To demonstrate its capability, the drug molecules (i.e., small-molecule drug doxorubicin, DOX) are continuously measured in the unprocessed whole blood of live animals (e.g., rats). The dynamic changes of drug concentrations with sub-minute temporal resolution are recorded for an extended period of time (∼8 hours). As an advance in remote diagnosis, this device would benefit the public by enabling long-distance precision medicine to prevent pandemics in advance.

Micro/nanofluidic devices integrated with ion concentration polarization (ICP) phenomenon have been used to preconcentrate low-abundant molecules for separation and detection purposes. This work reviews ICP-based devices focused on electrokinetic fundamentals of ICP in microfluidics and related design factors. We discuss various designs of ICP devices and then provide insight on the role of design factors in ICP function. In addition, fabrication methods and relevant materials for making ICP devices and nanojunctions are explained. This work provides the most up-to-date applications of ICP with emphasis on active and passive methods in controlling and stabilizing streams of preconcentrated molecules to enhance the separation and detection efficiency in diagnostics, desalination, and electrodialysis.

Cardiovascular disease is a chronic disease that leads to impaired cardiac function and requires long-term management to control its progression. Despite the importance of hydrogels for therapeutic applications, a contradiction between the size of a hydrogel and the amount of loaded drug has been encountered when using conventional fabrication methods. In this study, biocompatible reservoir microcapsules (diameter ∼100 μm) with a large liquid core and polymeric shell were fabricated via a one-step phase separation of poly(ethylene glycol)diacrylate (PEGDA) and dextran within pre-gel droplets through microfluidics. By controlling the process of phase separation, high drug-loading efficiency (∼80%) for long-term release (30 days) of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was achieved. Drug molecules were dispersed within the liquid core at a concentration above saturation solubility for sustained delivery via regulation of the shells. Effective therapeutic enhancement of human umbilical vein endothelial cell (HUVEC) and umbilical artery smooth muscle cell (SMC) proliferation and tube formation in vitro promoted rapid cell proliferation and increased the number of migrated cells by ∼1.7 times. Moreover, in vivo blood vessel regeneration for cardiovascular control induced by sustained dual-drug (VEGF and PDGF) delivery to the rat heart was achieved, showing the effectiveness of long-term protein delivery in improving cardiac function and significantly reducing ventricular wall thickness and fibrosis of the infarct region. The ratio of heart tissue scarring was reduced to 11.2% after microcapsule treatment compared with 21.4% after saline treatment in the rat model. By using these reservoir microcapsules, similar sustained delivery of proteins, mRNAs and biologic drugs could be developed for the treatment of a range of long-term chronic diseases and regenerative medicine.

Microfluidic paper-based analytical devices (μPADs) represent a modest and feasible alternative for conventional analytical methods. However, the inadequate sensitivity of these devices limits the possible applications of μPADs. In this scenario, inducing ion concentration polarization (ICP) on μPADs has shown promise to overcome this limitation by preconcentrating the analytes of interest. Here, we report a μPAD implementing ICP using an off-shelf Nafion® membrane as the perm selective membrane. Two types of devices with a geometrical configuration of a straight channel converging at the middle connecting to circular reservoirs at the end of channels were fabricated. The devices are comprised of a single input channel and an absorption channel. The Nafion membrane is attached to the absorption channel of the device, which is encased by heating with paraffin films at both sides to lower the electro-osmotic flow generated by an applied DC electric field that is needed for ICP. The field induced ICP enables obtaining a maximum concentration factor of more than 2000 folds for fluorescein sodium salt solution on the μPAD. Also, since evaporation of the sample solution was reported to be of great influence on the concentration factor, we analyze the effect of sample solution evaporation on sample preconcentration. Furthermore, our reported fabrication method for μPAD can lower the fabrication cost down to 0.3 USD. This device shows the potential to be developed for serving as a diagnostic and environmental monitoring platform.

We report a microfluidic paper based analytical device implementing ion concentration polarization (ICP) for rapid pre‐concentration of Escherichia coli in water. The fabricated device consists of a paper channel with a Nafion^® membrane and in‐built micro wire electrodes to supply electric voltage to induce the ICP effect. E. coli cells were stained with SYTO 9 and fluorescence was used as a sensing method. The device achieved high concentration factor up to 2 × 10⁵ within minutes. The effect of total ion concentration, on ICP and fluorescence intensity was studied. The reported device and method are suitable and effective for detection of E. coli during ballast water quality monitoring, coastal water quality monitoring where high salinity water is present.

Immunoassays are an important tool in various bioanalytical settings, such as clinical diagnostics, biopharmaceutical analysis, environmental monitoring, and food testing. An enzyme‐linked immunosorbent assay (ELISA) is usually used to amplify immunoassay signals; however, it requires labor‐intensive and time‐consuming procedures, which hinders its application to rapid cytokine detection. In this study, a nano‐in‐micro composite system, where immunosensing polystyrene beads (≈320 nm) are incorporated within a stimuli‐responsive microgel matrix (≈40 µm) via microfluidics, is investigated. The intrinsic volume phase‐transition change properties of the smart microgels allows an enzyme‐free enhanced immunoassay, enabling instant enhancement in signal‐to‐noise ratios of ≈5‐fold. This nano‐in‐micro hydrogel composite offers a simple yet highly effective method for sensitive and multiplexed cytokine analysis without complex enzyme‐based signal amplification steps, greatly benefitting advanced immune medicine.

Secreted proteins determine a range of cellular functionalities correlated with human health and disease progression. Because of cell heterogeneity, it is essential to measure low abundant protein secretions from individual cells to determine single‐cell activities. In this study, an integrated platform consisting of smart hydrogel immunosensors for the sensitive detection of single‐cell secretions is developed. A single cell and smart hydrogel microparticles are encapsulated within a droplet. After incubation, target secreted proteins from the cell are captured in the smart hydrogel particle for immunoassay. The temperature‐induced volume phase transition of the hydrogel biosensor allows the concentration of analytes within the gel matrix to increase, enabling high‐sensitivity measurements. Distinct heterogeneity for live cell secretions is determined from 6000 cells within 1 h. This method is tested for low abundant essential secretions, such as interleukin‐6, interleukin‐8, and monocyte chemoattractant protein‐1 secretions of both suspended cells (HL60) and adherent cells (MCF7 and MDA‐MB‐231). This platform is highly flexible and can be used to simultaneously measure a wide range of clinically relevant cellular secretions; it thus represents a novel tool for precise biological assays.

An ultrahigh-throughput single-cell miRNA assay is developed by a continuous-flow microfluidic process employing isothermal amplification to amplify the target miRNA signal.