Siphon-Induced Droplet Break-Off for Enhanced Mixing on a Centrifugal Platform

Abstract

We present a powerful and compact batch-mode mixing and dilution technique for centrifugal microfluidic platforms. Siphon structures are designed to discretize continuous flows into a sequence of droplets of volumes as low as 100 nL. Using a passive, self-regulating 4-step mechanism, discrete volumes of two fluids are alternatingly issued into a common intermediate chamber. At its base, a capillary valve acts as a fluidic shift register; a single droplet is held in place while two or more droplets merge and pass through the capillary stop. These merged droplets are advectively mixed as they pass through the capillary valve and into the receiving chamber. Mixing is demonstrated for various combinations of liquids such as aqueous solutions as well as saline solutions and human plasma. The mixing quality is assessed on a quantitative scale by using a colorimetric method based on the mixing of potassium thiocyanate and iron(III) chloride, and in the case of human plasma using a spectroscopic method. For instance, volumes of 5 µL have been mixed in less than 20 s. Single-step dilutions up to 1:5 of plasma in a standard phosphate buffer solution are also demonstrated. This work describes the preliminary development of the mixing method which has since been integrated into a commercially available microfluidic cartridge.Inventions 2020, 5, 1 2 of 14 microfluidic systems constitute a subset which uses the rotation of the chip, which is typically of a similar geometry as a Compact Disc™ or DVD™, to enable most pumping and valving operations. These systems can be further sub-divided into 'Bioanalytical Screening CDs' and 'Lab-on-a-Disc (LoaD)'. Bioanalytical screening CDs focus on adapting optical disc drive (ODD) technology (e.g., Compact Disc, DVD) for biological detection [9]. This technology takes advantage of the high-density data storage capability as well as the favorable pricing for its main constituents, i.e., the optical pickup unit, the spindle drive, and the optical disc substrates [10][11][12][13][14].The LoaD [15][16][17][18][19][20] is typically used to automate the standard laboratory steps conducted in a biology lab to enable a fully automated sample-to-answer system. The LoaD is particularly applicable for deployment in the field (point-of-use) or at the hospital bed-side (point-of-care) as the chips can be loaded at atmospheric pressure (via pipette or syrette) without issues regarding sealing or priming. The use of centrifugation for pumping also reduces the cost and complexity of support instrumentation as just low-cost spindle motors are required rather than specialized micropumps. Similarly, inherent centrifugation of samples [21][22][23] applied to sample preparation is a particular strength.The technological precursor of these systems are the centrifugal analyzers which became popular in the 1970s and 1980s [24] for automating a very limited number of simple assay steps, on rather macroscopic sample volumes, and readout on a rotor-based instrument. Currently the main areas of application are immuno...

Systematic Review of Centrifugal Valving Based on Digital Twin Modelling towards Highly Integrated Lab-on-a-Disc Systems

“…As (Ω) (22) in linear in ⁄ , also the radial product ̅ Δ (4) and thus Ω (23) remain unaltered for ⁄ = const. Hence, an LUO requiring retention of a different liquid volume keeps the same critical spin rate Ω (23) as long as the cross section of the inlet is adjusted by the same factor.…”

Systematic Review of Centrifugal Valving Based on Digital Twin Modelling towards Highly Integrated Lab-on-a-Disc Systems

“…In Figure A1, we fine-structure the original geometry for CP-DF siphoning of Figure 9; each compartment may have its specific depth, width and height to allow a wider space for multi-parameter optimization according to the performance metrics (26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Note that permanently gas-filled parts of the compression volume may be moved to "any" location available on the disc as long as it is connected by a pneumatic interconnect to the DF chamber.…”

“…In most such "Lab-on-a-Disc" (LoaD) systems, biochemical assay kits are ported on the rotationally controlled scheme by dissecting the often conventional, possibly volume-reduced protocol into a sequence of Laboratory Unit Operation (LUOs) such as metering / aliquoting [29][30][31], mixing [32][33][34][35], incubation, purification / concentration / extraction [36,37], homogenization [38,39], particle filtering [40][41][42][43][44][45] and droplet generation [46][47][48]. These LUOs are overwhelmingly processed in a batch-wise, rather than a continuous-flow fashion, by transiently sealing their fluidic exit with a normally-closed valve, thus intermittently stopping the flow while continuing rotation within certain boundaries, e.g., for vigorous agitation of the liquid sample.…”

Design Optimization of Centrifugal Microfluidic "Lab-on-a-Disc" Systems towards Fluidic Larger-Scale Integration

“…To this end, the bioanalytical protocols are dissected into laboratory unit operations (LUOs), each of them controlled by normally closed valve. Centrifugally implemented LUOs have been covered extensively in the literature, e.g., for metering / aliquoting [45][46][47], mixing [48][49][50][51], incubation, purification / concentration / extraction [35,52], homogenisation [53,54], particle filtering [55][56][57][58][59] and droplet generation [60][61][62].…”