Laser-actuated centrifugo-pneumatic flow control towards ‘sample-to-answer’ integrated detection of multi-marker panels at the point-of-care

Abstract

Point-of-care diagnostics devices require userfriendly automation of multi-step / multi-reagent bioanalytical protocols. We demonstrate, for the first time, Laser-actuated, Centrifugo-Pneumatic Valves (LCPVs) which open on-demand by ablating a remotely connected polymeric membrane with an instrument-based laser. Due to its small footprint, isolation of radiation-induced heating from the biological fluids and independence of radial position & contact-angle, the novel LCPV technology enables large-scale integration of flexibly customizable and operationally robust centrifugal microfluidic "Lab-on-a-Disc" (LoaD) systems. As a pilot application, we demonstrate the detection of Fatty Acid Binding Protein and Myeloperoxidase, both potential biomarkers used for cardiovascular disease (CVD) determination.

On-board reagent storage and release by solvent-selective, rotationally opened membranes: a digital twin approach

“…The permanently gas-filled parts of reservoirs may be placed at distal locations, as long as they are still pneumatically connected through conduits, e.g., to make efficient use of precious disc real estate required for multiplexed assay panels. The pneumatic seals may also be removed through a secondary mechanism, e.g., akin to venting procedures implemented for centrifugo-pneumatic valves based on mechanical (Kinahan et al 2016b), laser-(García-Cordero et al 2010Mishra et al 2018) or pneumatic (Keller et al 2015;Hess et al 2019;Kinahan et al 2016cKinahan et al , 2018Godino et al 2012Godino et al , 2013Schwemmer et al 2015a;Zhao et al 2015;Zehnle et al 2015;Ducrée 2021c;Mishra et al 2018;Gorkin et al 2010bGorkin et al , 2011Mark et al 2008Mark et al , 2009b principles.…”

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

“…After opening the DF at > Ω * > Ω (Figure 9, bottom, left), or by perforation of a seal (Figure 9c), the compression compartment is vented, i.e., ↦ ∞ and ↦ , and any spin rate > 0 will propel further liquid transfer (Figure 9, bottom, right). On the analogy of Figure 5, an additional seal or the DF might be opened by an external actuator [48,82], or by a preceding liquid handling step, e.g., through "event-triggering" [62]. This transfer of = ⋅ into the recess reduces the original liquid and gas volumes and + ⋅ , respectively, by , while the forward meniscus remains pinned to = − .…”

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

“…After opening the DF at > Ω * > Ω (Figure 9, bottom, left), or by perforation of a seal (Figure 9c), the pneumatic compartment is vented, i.e., ↦ ∞ and ↦ , and, consequently, any spin rate > 0 will propel further liquid transfer (Figure 9, bottom, right). On the analogy of Figure 5, an additional seal, or the DF, might be opened by an external actuator [71,116], or by a preceding liquid handling step, e.g., through "event-triggering" [90]. This transfer of = ⋅ into the recess reduces the original liquid and gas volumes and + ⋅ , respectively, by , and typically ≪ , while the forward meniscus remains pinned to = − .…”