Microfluidic chain reaction of structurally programmed capillary flow events

• Published in: Nature (London) Vol. 605; no. 7910; pp. 464 - 469
• Main Authors: Yafia, Mohamed, Ymbern, Oriol, Olanrewaju, Ayokunle O., Parandakh, Azim, Sohrabi Kashani, Ahmad, Renault, Johan, Jin, Zijie, Kim, Geunyong, Ng, Andy, Juncker, David
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.05.2022; Nature Publishing Group
• Subjects: 631/1647/277; 639/166/985; 639/638/11/277; 82/62; Algorithms; Antibodies; Automation; Biotechnology; Capillary flow; Coagulation; Coronaviruses; COVID-19; Design; Flow control; Free energy; Humanities and Social Sciences; Humans; Integrated circuits; Iterative methods; Lab-on-a-chip; Lab-On-A-Chip Devices; Laboratories; Microfluidic Analytical Techniques - methods; Microfluidics; Microfluidics - methods; multidisciplinary; Parallel operation; Polymerase Chain Reaction; Propagation; Reagents; Retention; Saliva; SARS-CoV-2 - genetics; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Thrombin; Timing devices; Valves
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-022-04683-4

Chain reactions, characterized by initiation, propagation and termination, are stochastic at microscopic scales and underlie vital chemical (for example, combustion engines), nuclear and biotechnological (for example, polymerase chain reaction) applications 1 , 2 , 3 , 4 – 5 . At macroscopic scales, chain reactions are deterministic and limited to applications for entertainment and art such as falling dominoes and Rube Goldberg machines. On the other hand, the microfluidic lab-on-a-chip (also called a micro-total analysis system) 6 , 7 was visualized as an integrated chip, akin to microelectronic integrated circuits, yet in practice remains dependent on cumbersome peripherals, connections and a computer for automation 8 , 9 , 10 – 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 , 13 , 14 , 15 , 16 , 17 , 18 – 19 . Here we introduce the microfluidic chain reaction (MCR) as the conditional, structurally programmed propagation of capillary flow events. Monolithic chips integrating a MCR are three-dimensionally printed, and powered by the free energy of a paper pump, autonomously execute liquid handling algorithms step-by-step. With MCR, we automated (1) the sequential release of 300 aliquots across chained, interconnected chips, (2) a protocol for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies detection in saliva and (3) a thrombin generation assay by continuous subsampling and analysis of coagulation-activated plasma with parallel operations including timers, iterative cycles of synchronous flow and stop-flow operations. MCRs are untethered from and unencumbered by peripherals, encode programs structurally in situ and can form a frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics. Microfluidic chain reactions encode programs structurally in situ, and can form a frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics