Systematic review of centrifugal valving based on digital twin modeling towards highly integrated lab-on-a-disc systems

Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control which mainly depend on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates efficient simulation tools for virtual prototyping and characterization and algorithmic design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, layout, fluidic testing, bioanalytical validation, and scale-up to commercial mass manufacture.

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

Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control mainly based on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates the provision of efficient simulation tools for virtual prototyping and characterization to greatly expedite design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, fluidic testing, bioanalytical validation and scale-up to commercial mass manufacture.

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

Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control mainly based on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates the provision of efficient simulation tools for virtual prototyping and characterization to greatly expedite design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, fluidic testing, bioanalytical validation and scale-up to commercial mass manufacture.

Cell-Based In Vitro Assay Automation: Balancing Technology and Data Reproducibility/Predictability

G-protein-coupled receptors (GPCRs) are modulated by many marketed drugs, and as such, they continue to be key targets for drug discovery and development. Many GPCR targets at Merck Research Laboratories (MRL) are profiled using homogenous time-resolved fluorescence (HTRF) inositol monophosphate (IP-1) cell-based functional assays using adherent cells in 384-well microplates. Due to discrepancies observed across several in vitro assays supporting lead optimization structure–activity relationship (SAR) efforts, different assay paradigms were evaluated for removing growth medium from the assay plates prior to compound addition and determination of IP-1 accumulation. Remarkably, employing the noncontact centrifugation BlueWasher method leads to left-shifted potencies across multiple structural classes and rescues “false negatives” relative to the traditional manual evacuation method. Further, assay performance is improved, with the minimum significant ratio of challenging chemotypes dropping from ~5–6 to <3. While the impact of BlueWasher on a broad range of our GPCR targets remains to be determined, for highly protein-bound small molecules, it provides a path toward improving assay reproducibility across scientists and sites as well as reducing replicates in SAR assay support.

Understanding partial saturation in paper microfluidics enables alternative device architectures

A closer look at flow in paper microfluidic devices enables more advanced diagnostic assay automation using the same inexpensive materials.

Thermally-Triggered Effervescent Mixing for Assay Automation

<div>Meltable barriers are an attractive means to achieve controlled delivery of reagents in a variety of settings, enabling assays to be performed through thermal automation instead of manual addition of reactants. However, mixing kinetics in such systems can be slow due to the lack of active flow or mechanical shaking. We demonstrate a new strategy for hands-free, thermally-automated agitation of biochemical reactions. Reagents for binary effervescent reactions are lyophilized then capped with a phase-change partition, eicosane. This barrier can be melted at moderate temperatures, at which point an aqueous solution dissolves the reactants, generating bubbles that mix the solution through convection. We explore reactions that generate bubbles of carbon dioxide and oxygen gasses, characterizing the induced mixing rate of two aqueous solutions with dissimilar densities. This strategy affords control over the initiation and duration of convective mixing, providing a tool for thermal automation of biochemical reactions with efficient reaction kinetics.</div>

Thermally-Triggered Effervescent Mixing for Assay Automation

<div>Meltable barriers are an attractive means to achieve controlled delivery of reagents in a variety of settings, enabling assays to be performed through thermal automation instead of manual addition of reactants. However, mixing kinetics in such systems can be slow due to the lack of active flow or mechanical shaking. We demonstrate a new strategy for hands-free, thermally-automated agitation of biochemical reactions. Reagents for binary effervescent reactions are lyophilized then capped with a phase-change partition, eicosane. This barrier can be melted at moderate temperatures, at which point an aqueous solution dissolves the reactants, generating bubbles that mix the solution through convection. We explore reactions that generate bubbles of carbon dioxide and oxygen gasses, characterizing the induced mixing rate of two aqueous solutions with dissimilar densities. This strategy affords control over the initiation and duration of convective mixing, providing a tool for thermal automation of biochemical reactions with efficient reaction kinetics.</div>

The LabTube – a novel microfluidic platform for assay automation in laboratory centrifuges

Based on a centrifugally-controlled ballpen-mechanism, the LabTube enables cost-efficient assay automation at even low sample throughput using standard centrifuges.