Microfluidic Chain Reaction

Chain reactions are characterized by initiation, propagation and termination, are stochastic at microscopic scales and underlie vital chemical (e.g. combustion engines), nuclear and biotechnological (e.g. polymerase chain reaction) applications.1–5 At macroscopic scales, chain reactions are deterministic and limited to applications for entertainment and art such as falling domino and Rube Goldberg machines. Appositely, microfluidic lab-on-a-chip (also called a micro total analysis system),6,7 which were envisioned pursuant to microelectronic integrated circuits, are generally not integrated on a chip owing to an enduring dependency on cumbersome connections, peripherals, and on computers for automation.8–11 Capillary microfluidics integrate energy supply and flow control onto a single chip by using capillary phenomena, but programmability remains rudimentary with at most a handful (eight) operations possible.12–19 Here we introduce mesoscopic microfluidic chain reactions (MCRs) based on capillary phenomena for reliable programming and automation of complex liquid handling algorithms integrated in a chip. MCRs are encoded into the chip microarchitecture, 3D printed as a monolithic circuit, and deterministically propagated by the free-energy of a paper pump. With MCR, we sequentially triggered the release of 300 aliquots across chained, interconnected chips, and automated a protocol for SARS-CoV-2 antibodies detection in saliva with visual and quantitative results by cell phone imaging. We automated and miniaturized for the first time the labor-intensive thrombogram with serial and parallel operations including timers and iterative cycles of synchronous flow and stop-flow sequences. Thrombograms with normal, hemophilia-like, and anticoagulant-spiked plasma were generated. MCRs are generalizable, and both the density and number of chain reaction units are scalable. MCRs are untethered from and unencumbered by peripherals, encode programs structurally in situ, and form a frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics.