Digital process control of multi-step assays on centrifugal platforms using high-low-high rotational-pulse triggered valving

Due to their capability for comprehensive sample-to-answer automation, the interest in centrifugal microfluidic systems has greatly increased in industry and academia over the last quarter century. The main applications of these Lab-on-a-Disc (LoaD) platforms are in decentralised bioanalytical point-of-use / point-of-care testing. Due to the unidirectional and omnipresent nature of the centrifugal force, advanced flow control is key to coordinate multi-step / multi-reagent assay formats on the LoaD. Formerly, flow control was often achieved by capillary burst valves which require gradual increments of the spin speed of the system-innate spindle motor. Recent advanced introduced a flow control scheme called 'rotational pulse actuated valves'. In these valves the sequence of valve actuation is determined by the architecture of the disc while actuation is triggered by freely programmable upward spike (i.e. Low-High-Low (LHL)) in the rotational frequency. This paradigm shift from conventional 'analogue' burst valves to 'digital' pulsing significantly increases the number of sequential while also improving the overall robustness of flow control. In this work, we expand on these LHL valves by introducing High-Low-High (HLH) pulse-actuated (PA) valving which are actuated by 'downward' spike in the disc spin-rate. These HLH valves are particularly useful for high spin-rate operations such as centrifugation of blood. We introduce two different HLH architectures and then combine the most promising with LHL valves to implement the time-dependent liquid handling protocol underlying a common liver function test panel.

Automated summary

Due to the automation capabilities of centrifugal microfluidic systems, they have gained significant interest in industry and academia over the past 25 years. These systems, also known as Lab-on-a-Disc platforms, are primarily used for decentralized bioanalytical point-of-use/point-of-care testing. Flow control plays a crucial role in coordinating multi-step/multi-reagent assay formats on these platforms. Traditional flow control methods, such as capillary burst valves, have been replaced by programmable rotational pulse actuated valves, which use digital pulsing to improve flow control. In this work, High-Low-High (HLH) pulse-actuated valves are introduced for high spin-rate operations, such as blood centrifugation. The combination of HLH valves with Low-High-Low (LHL) valves is used to implement a time-dependent liquid handling protocol for a liver function test panel.