The SlipChip is a microfluidic device designed to perform multiplexed microfluidic reactions without pumps or valves. The device has two plates in close contact. The bottom plate contains wells preloaded with many reagents; in this paper plates with 48 reagents were used. These wells are covered by the top plate that acts as a lid for the wells with reagents. The device also has a fluidic path, composed of ducts in the bottom plate and wells in the top plate, which is connected only when the top and bottom plate are aligned in a specific configuration. Sample can be added into the fluidic path, filling both wells and ducts. Then, the top plate is “slipped”, or moved, relative to the bottom plate so the complementary patterns of wells in both plates overlap, exposing the sample-containing wells of the top plate to the reagent-containing wells of the bottom plate, and enabling diffusion and reactions. Between the two plates, a lubricating layer of fluorocarbon was used to facilitate relative motion of the plates. This paper implements this approach on a nanoliter scale using devices fabricated in glass. Stability of preloaded solutions, control of loading, and lack of cross-contamination were tested using fluorescent dyes. Functionality of the device was illustrated via crystallization of a model membrane protein. Fabrication of this device is simple and does not require a bonding step. This device requires no pumps or valves and is applicable to resource-poor settings. Overall, this device should be valuable for multiplexed applications that require exposing one sample to many reagents in small volumes. One may think of the SlipChip as an easy-to-use analogue of a preloaded multi-well plate, or a preloaded liquid-phase microarray.

The SARS-CoV-2 pandemic has created an unprecedented need for rapid diagnostic testing to enable the efficient treatment and mitigation of COVID-19. The primary diagnostic tool currently employed is reverse transcription polymerase chain reaction (RT-PCR), which can have good sensitivity and excellent specificity. Unfortunately, implementation costs and logistical problems with reagents during the global SARS-CoV-2 pandemic have hindered its universal on demand adoption. Lateral flow assays (LFAs) represent a class of diagnostic that, if sufficiently clinically sensitive, may fill many of the gaps in the current RT-PCR testing regime, especially in low- and middle-income countries (LMICs). To date, many serology LFAs have been developed, though none meet the performance requirements necessary for diagnostic use cases, primarily due to the relatively long delay between infection and seroconversion. However, on the basis of previously reported results from SARS-CoV-1, antigen-based SARS-CoV-2 assays may have significantly better clinical sensitivity than serology assays. To date, only a very small number of antigen-detecting LFAs have been developed. Development of a half-strip LFA is a useful first step in the development of any LFA format. In this work, we present a half-strip LFA using commercially available antibodies for the detection of SARS-CoV-2. We have tested this LFA in buffer and measured an LOD of 0.65 ng/mL (95% CI of 0.53 to 0.77 ng/mL) ng/mL with recombinant antigen using an optical reader with sensitivity equivalent to a visual read. Further development, including evaluating the appropriate sample matrix, will be required for this assay approach to be made useful in a point of care setting, though this half-strip LFA may serve as a useful starting point for others developing similar tests.

This paper describes a SlipChip-based approach to perform bead-based heterogeneous immunoassays with multiple nanoliter-volume samples. As a potential device to analyze the output of the chemistrode, the performance of this platform was tested using low concentrations of biomolecules. Two strategies to perform the immunoassay in the SlipChip were tested: 1) a unidirectional slipping method to combine the well containing a sample with a series of wells preloaded with reagents; 2) a back-and-forth slipping method to introduce a series of reagents to a well containing the sample by reloading and slipping the well containing the reagent. The SlipChips were fabricated with hydrophilic surfaces on the interior of the wells and with hydrophobic surfaces on the face of the SlipChip to enhance filling, transferring, and maintaining aqueous solutions in shallow wells. Nanopatterning was used to increase the hydrophobic nature of the SlipChip surface. Magnetic beads containing the capture antibody were efficiently transferred between wells and washed by serial dilution. An insulin immunoenzymatic assay showed a detection of limit of ~13 pM. Forty eight droplets of nanoliter volume were analyzed in parallel, including an on-chip calibration. The design of the SlipChip is flexible to accommodate other types of immunoassays, both heterogeneous and homogeneous. This work establishes the possibility of using SlipChip-based immunoassays in small volumes for a range of possible applications, including analysis of plugs from a chemistrode, detection of molecules from single cells, and diagnostic monitoring.

Chemicals and MaterialsAll experiments were conducted using chemicals of at least analytical reagent grade, received from Fisher Scientific and Sigma-Aldrich. Bis-(2-ethylhexyl) phosphoric acid (HDEHP) was received from Alfa-Aesar and purified using a Cu salt precipitation method 1 . Lanthanide stock solution was prepared using Ln nitrates of 99.99% purity. Experimental Section Laser machining of tubing and assembly of the deviceThe organic withdrawal channels were laser machined from 1/32" Teflon® FEP tubing. A Resontics RapidX 250 was utilized to machine all tubing substrates referenced within. A laser lathe stage was utilized to rotate the tubing 72º after the completion of each hole, until all 5 holes were drilled. Channel size was verified using a calibrated stereoscope. Figure S1 shows cross sections of tubing before and after machining. Figure S2 shows the details of how the device was assembled.

We performed electrowetting (EW) contact angle measurements to determine the interfacial tension between aqueous drops laden with various inorganic and organic solutes and various ambient oils. Using low frequency AC voltage, we obtained interfacial tensions from 5 to 72 mJ/m 2, in close agreement with macroscopic tensiometry for drop volumes between 20 and 2000 nL. In addition to the conventional EW geometry, we demonstrate the possibility of performing "contact-less" measurements without any loss of accuracy using interdigitated coplanar electrodes.