We present a microfluidic device for the capture and release of circulating exosomes from human blood. The exosome-specific dual-patterned immunofiltration (ExoDIF) device is composed of two distinct immuno-patterned layers, and is capable of enhancing the chance of binding between the antibody and exosomes by generating mechanical whirling, thus achieving high-throughput exosome isolation with high specificity. Moreover, follow-up recovery after the immuno-affinity based isolation, via cleavage of a linker, enables further downstream analysis. We verified the performance of the present device using MCF-7 secreted exosomes and found that both the concentration and proportion of exosome-sized vesicles were higher than in the samples obtained from the conventional exosome isolation kit. We then isolated exosomes from the human blood samples with our device to compare the exosome level between cancer patients and healthy donors. Cancer patients show a significantly higher exosome level with higher selectivity when validating the exosome-sized vesicles using both electron microscopy and nanoparticle tracking analysis. The captured exosomes from cancer patients also express abundant cancer-associated antigens, the epithelial cell adhesion molecule (EpCAM) on their surface. Our simple and rapid exosome recovery technique has huge potential to elucidate the function of exosomes in cancer patients and can thus be applied for various exosome-based cancer research studies.

A human stress monitoring patch integrates three sensors of skin temperature, skin conductance, and pulsewave in the size of stamp (25 mm × 15 mm × 72 μm) in order to enhance wearing comfort with small skin contact area and high flexibility. The skin contact area is minimized through the invention of an integrated multi-layer structure and the associated microfabrication process; thus being reduced to 1/125 of that of the conventional single-layer multiple sensors. The patch flexibility is increased mainly by the development of flexible pulsewave sensor, made of a flexible piezoelectric membrane supported by a perforated polyimide membrane. In the human physiological range, the fabricated stress patch measures skin temperature with the sensitivity of 0.31 Ω/°C, skin conductance with the sensitivity of 0.28 μV/0.02 μS, and pulse wave with the response time of 70 msec. The skin-attachable stress patch, capable to detect multimodal bio-signals, shows potential for application to wearable emotion monitoring.

We propose watch-type sweat rate sensors capable of automatic natural ventilation by integrating miniaturized thermo-pneumatic actuators, and experimentally verify their performances and applicability. Previous sensors using natural ventilation require manual ventilation process or high-power bulky thermo-pneumatic actuators to lift sweat rate detection chambers above skin for continuous measurement. The proposed watch-type sweat rate sensors reduce operation power by minimizing expansion fluid volume to 0.4 ml through heat circuit modeling. The proposed sensors reduce operation power to 12.8% and weight to 47.6% compared to previous portable sensors, operating for 4 hours at 6 V batteries. Human experiment for thermal comfort monitoring is performed by using the proposed sensors having sensitivity of 0.039 (pF/s)/(g/m²h) and linearity of 97.9% in human sweat rate range. Average sweat rate difference for each thermal status measured in three subjects shows (32.06 ± 27.19) g/m²h in thermal statuses including ‘comfortable’, ‘slightly warm’, ‘warm’, and ‘hot’. The proposed sensors thereby can discriminate and compare four stages of thermal status. Sweat rate measurement error of the proposed sensors is less than 10% under air velocity of 1.5 m/s corresponding to human walking speed. The proposed sensors are applicable for wearable and portable use, having potentials for daily thermal comfort monitoring applications.

We present passive flow-rate regulators using an autonomous deflection of parallel membrane valves, capable to maintain a constant flow-rate at varying inlet pressure supplied from micropumps. The previous passive flow-rate regulators are difficult to integrate with micropumps, not only because of the complex multi-layer structures, but also because of the high threshold inlet pressure required for flow-rate regulation. In this study, we present passive flow-rate regulators using parallel membrane valves, capable of achieving flow-rate regulation function at the minimum threshold inlet pressure as low as 15 kPa with simple structure formed by a single mask process. The parallel membranes in a flow-rate regulator are designed to deflect and adjust flow resistance autonomously according to the inlet pressure, thus maintaining a constant flow-rate independent of the inlet pressure variation. We designed the four different prototypes of W20, W30, W40, and W50, having parallel membrane widths of 20, 30, 40 and 50 µm, respectively. We estimated the flow-rate based on both analytical and numerical models. In an experimental study, we observed the deformation of parallel membranes and the flow-rate depending on the inlet pressure. The fabricated prototypes achieved the constant flow-rate of 6.09 ± 0.32 µl s⁻¹ (W20 fabricated by 10 : 1 PDMS (PolyDiMethylSiloxane)) over an inlet pressure of 20 kPa. We also observed that prototypes fabricated by 20 : 1 PDMS, having lower Young's modulus than normal 10 : 1 PDMS, showed a lower threshold pressure and higher regulated flow-rate than prototypes fabricated by 10 : 1 PDMS. W40 fabricated by 20 : 1 PDMS showed a constant flow-rate of 14.53 ± 0.51 µl s⁻¹ over inlet pressure of 15 kPa. The present passive flow-rate regulators have strong potential for applications in integrated microfluidic systems.

We present a continuous size-dependent particle separator using a negative dielectrophoretic (DEP) virtual pillar array. Two major problems in the previous size-dependent particle separators include the particle clogging in the mechanical sieving structures and the fixed range of separable particle sizes. The present particle separator uses the virtual pillar array generated by negative DEP force instead of the mechanical pillar array, thus eliminating the clogging problems. It is also possible to adjust the size of separable particles since the size of virtual pillars is a function of a particle diameter, applied voltage, flow rate, etc. At an applied voltage of 500 kHz, 10 V_rms (root mean sqaure voltage) sinusoidal wave and a flow rate of 0.40 μl min⁻¹, we separate 5.7 ± 0.28 μm-, 8.0 ± 0.80 μm-, 10.5 ± 0.75 μm-, and 11.9 ± 0.12 μm-diameter polystyrene (PS) beads with a separation purity of 95%, 92%, 50%, and 63%, respectively. The 10.5 μm- and 11.9 μm-diameter PS beads have relatively low separation purity of 50% and 63%. However, at an applied voltage of 8 V_rms, we separate 11.9 μm-diameter PS beads with a separation purity over 99%. At an applied voltage of 500 kHz, 10 V_rms sinusoidal wave and a flow rate of 0.11 μl min⁻¹, we separate red blood cells (5.4 ± 1.3 μm-diameter) and white blood cells (8.1 ± 1.5 μm-diameter) with a separation purity over 99%. Therefore, the present particle separator achieves clog-free, size-dependent particle separation, which is capable of size tuning of separable particles.

The present research proposes the present porous polydimethylsiloxane (PDMS) layer for the skin trouble reduced daily life skin attachable devices. The present research proposes the new pores forming method in the PDMS by crystallization and dissolution of the citric acid in the PDMS for fabricating high uniform and small size pores. The present porous PDMS layer (i) decreases the pore size 93.2%p and increases the pore size uniformity 425%p compared to the conventional porous PDMS layer of mixing sugars and PDMS; (ii) is able to be fabricated in the thickness of 21–101 µm by spin-coating; (iii) has the 2.2 times higher water vapor transmission rate (947 ± 10.8 g/day•m²) compared to the human skin water vapor transmission rate. The present porous PDMS layer reduces the skin trouble effectively by having the high water vapor permeability, therefore is applicable to the human daily-life skin attachable devices.