Reliable, autonomous, internally self-powered microfluidic pumps are in critical demand for rapid point-of-care (POC) devices, integrated molecular-diagnostic platforms, and drug delivery systems. Here we report on a Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation (SIMPLE), which is disposable, autonomous, easy to use and fabricate, robust, and cost efficient, as a solution for self-powered microfluidic POC devices. The imbibition pump introduces the working liquid which is sucked into a porous material (paper) upon activation. The suction of the working liquid creates a reduced pressure in the analytical channel and induces the sequential sample flow into the microfluidic circuits. It requires no external power or control and can be simply activated by a fingertip press. The flow rate can be programmed by defining the shape of utilized porous material: by using three different paper shapes with circular section angles 20°, 40° and 60°, three different volume flow rates of 0.07 μL s(-1), 0.12 μL s(-1) and 0.17 μL s(-1) are demonstrated at 200 μm × 600 μm channel cross-section. We established the SIMPLE pumping of 17 μL of sample; however, the sample volume can be increased to several hundreds of μL. To demonstrate the design, fabrication, and characterization of SIMPLE, we used a simple, robust and cheap foil-laminating fabrication technique. The SIMPLE can be integrated into hydrophilic or hydrophobic materials-based microfluidic POC devices. Since it is also applicable to large-scale manufacturing processes, we anticipate that a new chapter of a cost effective, disposable, autonomous POC diagnostic chip is addressed with this technical innovation.

Bead-based microwell array technology is growing as an ultrasensitive analysis tool as exemplified by the successful commercial applications from Illumina and Quanterix for nucleic acid analysis and ultrasensitive protein measurements, respectively. High-efficiency seeding of magnetic beads is key for these applications and is enhanced by hydrophilic-in-hydrophobic microwell arrays, which are unfortunately often expensive or labor-intensive to manufacture. Here, we demonstrate a new single-step manufacturing approach for imprinting cheap and disposable hydrophilic-in-hydrophobic microwell arrays suitable for digital bioassays. Imprinting of arrays with hydrophilic-in-hydrophobic microwells is made possible using an innovative surface energy replication approach by means of a hydrophobic thiol-ene polymer formulation. In this polymer, hydrophobic-moiety-containing monomers self-assemble at the hydrophobic surface of the imprinting stamp, which results in a hydrophobic replica surface after polymerization. After removing the stamp, microwells with hydrophobic walls and a hydrophilic bottom are obtained. We demonstrate that the hydrophilic-in-hydrophobic imprinted microwell arrays enable successful and efficient self-assembly of individual water droplets and seeding of magnetic beads with loading efficiencies up to 96%. We also demonstrate the suitability of the microwell arrays for the isolation and digital counting of single molecules achieving a limit of detection of 17.4 aM when performing a streptavidin-biotin binding assay as model system. Since this approach is up-scalable through reaction injection molding, we expect it will contribute substantially to the translation of ultrasensitive digital microwell array technology toward diagnostic applications.

Single cell analysis (SCA) has gained increased popularity for elucidating cellular heterogeneity at genomic, proteomic and cellular levels. Flow cytometry is considered as one of the most widely used techniques to characterize single cell responses; however, its inability to analyse cells with spatio-temporal resolution poses a major drawback. Here, we introduce a digital microfluidic (DMF) platform as a useful tool for conducting studies on isolated yeast cells in a high-throughput fashion. The reported system exhibits (i) a microwell array for trapping single non-adherent cells by shuttling a cell-containing droplet over the array, and allows (ii) implementation of high-throughput cytotoxicity assays with enhanced spatio-temporal resolution. The system was tested for five different concentrations of the antifungal drug Amphotericin B, and the cell responses were monitored over time by time lapse fluorescence microscopy. The DMF platform was validated by bulk experiments, which mimicked the DMF experimental design. A correlation analysis revealed that the results obtained on the DMF platform are not significantly different from those obtained in bulk; hence, the DMF platform can be used as a tool to perform SCA on non-adherent cells, with spatio-temporal resolution. In addition, no external forces, other than the physical forces generated by moving the droplet, were used to capture single cells, thereby avoiding cell damage. As such, the information on cellular behaviour during treatment could be obtained for every single cell over time making this platform noteworthy in the field of SCA.

No abstract

In this work, we present a new iSIMPLE concept (infusion Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation), which requires no external power for activation nor liquid manipulation, it is easy to use while its fabrication method is extremely simple, inexpensive and suited for mass replication. The pump consists of a working liquid, which is - after finger activation - absorbed in a porous material (e.g. filter paper). The air expelled from the porous material increases the pressure in the downstream outlet channel and propels the outlet liquid (i.e. the sample) through the channel or ejects it. Here we investigated the influence of different filter papers on the iSIMPLE flow rates, achieving a wide range from 30 down to 0.07 μL/min. We also demonstrated the versatility of the iSIMPLE in terms of the liquid volume that can be manipulated (from 0.5 μL up to 150 μL) and the working pressure reaching 64 kPa, unprecedented high for a self-powered microfluidics pump. In addition, using a 34 G microneedle mounted on the iSIMPLE, we successfully injected liquids with different viscosities (from 0.93 up to 55.88 cP) both into an agarose matrix and a skin-like biological ex vivo substrate (i.e. chicken breast tissue). This work validated the compatibility of the iSIMPLE with drug delivery in a controlled way into a skin-like matrix, envisioning a whole new scenario for intradermal injections using self-contained skin patch. In addition, due to the extreme flexibility of the design and manufacturing, the iSIMPLE concept offers enormous opportunities for completely autonomous, portable and cost effective LOC devices.

Inspired by human skin that dissipates heat via sweat-droplet evaporation on the skin, we propose an evaporative cooling technique via arrayed-droplets on a porous membrane, construct an analytical model of the evaporative cooling including interactions among the large number of droplets, and extensively analyze the cooling performance of 1000-droplet array. Our model shows that heat dissipation is enhanced by the membrane with dense droplets ͑i.e., enhancement factor of 10 at 5000 pores/ cm 2 and pore radius of 35 m with respect to human skin͒. Additionally, the model predicts that the membrane dissipates heat more efficiently by operating at a higher temperature ͑i.e., additional enhancement factor of 17 at droplet temperature of 100°C͒.

The lab-on-a-chip (LOC) field has witnessed an excess of new technology concepts, especially for the point-of-care (POC) applications. However, only few concepts reached the POC market often because of challenging integration with pumping and detection systems as well as with complex biological assays. Recently, a new technology termed SIMPLE was introduced as a promising POC platform due to its features of being self-powered, autonomous in liquid manipulations, cost-effective and amenable to mass production. In this paper, we improved the SIMPLE design and fabrication and demonstrated for the first time that the SIMPLE platform can be successfully integrated with biological assays by quantifying creatinine, biomarker for chronic kidney disease, in plasma samples. To validate the robustness of the SIMPLE technology, we integrated a SIMPLE-based microfluidic cartridge with colorimetric read-out system into the benchtop Creasensor. This allowed us to perform on-field validation of the Creasensor in a single-blind study with 16 plasma samples, showing excellent agreement between measured and spiked creatinine concentrations (ICC: 0.97). Moreover, the range of clinically relevant concentrations (0.76-20 mg/dL), the sample volume (5 μL) and time-to-result of only 5 min matched the Creasensor performance with both lab based and POC benchmark technologies. This study demonstrated for the first time outstanding robustness of the SIMPLE in supporting the implementation of biological assays. The SIMPLE flexibility in liquid manipulation and compatibility with different sample matrices opens up numerous opportunities for implementing more complex assays and expanding its POC applications portfolio.

The detection of single molecules in magnetic microbead microwell array formats revolutionized the development of digital bioassays. However, retrieval of individual magnetic beads from these arrays has not been realized until now despite having great potential for studying captured targets at the individual level. In this paper, optical tweezers were implemented on a digital microfluidic platform for accurate manipulation of single magnetic beads seeded in a microwell array. Successful optical trapping of magnetic beads was found to be dependent on Brownian motion of the beads, suggesting a 99% chance of trapping a vibrating bead. A tailor-made experimental design was used to screen the effect of bead type, ionic buffer strength, surfactant type, and concentration on the Brownian activity of beads in microwells. With the optimal conditions, the manipulation of magnetic beads was demonstrated by their trapping, retrieving, transporting, and repositioning to a desired microwell on the array. The presented platform combines the strengths of digital microfluidics, digital bioassays, and optical tweezers, resulting in a powerful dynamic microwell array system for single molecule and single cell studies.