Network simulation-based optimization of centrifugo-pneumatic blood plasma separation

Abstract

Automated and robust separation of 14 l of plasma from 40l of whole blood at a purity of 99.81% ± 0.11% within 43 s is demonstrated for the hematocrit range of 20%-60% in a centrifugal microfluidic polymer disk. At high rotational frequency, red blood cells (RBCs) within whole blood are concentrated in a radial outer RBC collection chamber. Simultaneously, plasma is concentrated in a radial inner pneumatic chamber, where a defined air volume is enclosed and compressed. Subsequent reduction of the rotational frequency to not lower than 25 Hz enables rapid transfer of supernatant plasma into a plasma collection chamber, with highly suppressed resuspension of red blood cells. Disk design and the rotational protocol are optimized to make the process fast, robust, and insusceptible for undesired cell resuspension. Numerical network simulation with lumped model elements is used to predict and optimize the fluidic characteristics. Lysis of the remaining red blood cells in the purified plasma, followed by measurement of the hemoglobin concentration, was used to determine plasma purity. Due to the pneumatic actuation, no surface treatment of the fluidic cartridge or any additional external means are required, offering the possibility for low-cost mass fabrication technologies, such as injection molding or thermoforming.

Mathematical modeling and computational analysis of centrifugal microfluidic platforms: a review

“…In this method, the interface is detected as the zero value of a level set scalar parameter known as ϕ. This parameter can be defined as eqn (49 For the condition in which some slug fluids are to be mixed, other models are more appropriate, including the coupling of Navier-Stokes equations with the phase-field equations. In comparison with the level-set model, this model involves more computational and time costs.…”

“…Later, Zehnle et al (2017) used the network simulation to design and optimize a centrifugo-pneumatic blood plasma separation unit. 49 As depicted in Fig. 24(D), a pneumatic chamber was pressurized by centrifugal force.…”

“…The diagram shows the comparison of simulation and experimental results for the filling level of the siphon valve (l 1 ) and pneumatic chamber (l 2 ) together with rotational frequency over time. 49 Reprinted with the permission of AIP Publishing. (E) Schematic figure of the LOD inertia pumping simulated by Asiaei et al 48 Reprinted with the permission of IOP Publishing.…”

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

“…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

“…In most LoaD systems, these valves retain the liquid during so-called laboratory unit operations ("LUOs"), such metering and mixing, as extensively covered in the literature [48,[53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72], and briefly in a subsequent section within the context of LSI. Furthermore, while essential ingredients for fullfledged LoaD applications, we refer to the numerous specialized publications regarding the many, primarily optical or electrochemical, techniques for downstream detection [18-37, 73, 74].…”