title: Power-free, digital and programmable dispensing of picoliter droplets using a Digit Chip.
abstract: There is a growing need for power-free methods to manipulate small volumes of liquids and thereby enable use of diagnostic assays in resource-limited settings. Most existing self-powered devices provide analog manipulation of fluids using paper, capillary or pressure-driven pumps. These strategies are well-suited to manipulating larger micro- and milliliter-scale volumes at constant flow rates; however, they fail to enable the manipulation of nanoliter and picoliter volumes required in assays using droplets, capillary sampling (e.g. finger prick), or expensive reagents. Here we report a device, termed the Digit Chip, that provides programmable and power-free digital manipulation of sub-nanoliter volumes. The device consists of a user-friendly button interface and a series of chambers connected by capillary valves that serve as digitization elements. Via a button press, the user dispenses and actuates ultra-small, quantitatively-programmed volumes. The device geometry is optimized using design models and experiments and precisely dispenses volumes as low as 21 pL with 97% accuracy. The volume dispensed can be tuned in 10 discrete steps across one order-of-magnitude with 98% accuracy. As a proof-of-principle that nanoliter-scale reagents can be precisely actuated and combined on-chip, we deploy the device to construct a precise concentration gradient with 10 discrete concentrations. Additionally, we apply this device alongside an inexpensive smartphone-based fluorescence imaging platform to perform a titration of E. coli with ampicillin. We observe the onset of bacterial death at a concentration of 5 μg mL-1, increasing to a maximum at 50 μg mL-1. These results establish the utility of the Digit Chip for diagnostic applications in low-resource environments.
authors.affiliation: Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada. shana.kelley@utoronto.ca.
authors.forename: A
authors.initials: A
authors.lastname: Mepham
authors.forename: J D
authors.initials: JD
authors.lastname: Besant
authors.forename: A W
authors.initials: AW
authors.lastname: Weinstein
authors.forename: I B
authors.initials: IB
authors.lastname: Burgess
authors.forename: E H
authors.initials: EH
authors.lastname: Sargent
authors.forename: S O
authors.initials: SO
authors.lastname: Kelley
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004867:Equipment Design; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D008962:Models, Theoretical; D010316:Particle Size; D011312:Pressure; D014584:User-Computer Interface
chemical_list: D000900:Anti-Bacterial Agents; D000667:Ampicillin