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.