Significance Lab-on-a-chip devices aim to miniaturize laboratory procedures on microfluidic chips, which contain liquid circuits instead of electronics. Although the chips themselves are small, they are typically dependent on off-chip control machinery that negates their size advantage. If a computer controller could be built out of microfluidic valves and channels, it could be integrated to create a complete system-on-a-chip. We engineer a critical component for such a computer: a microfluidic clock oscillator with suitable timing accuracy to control diagnostic assays. Further, we leverage this oscillator to build a self-driving pump for on-chip liquid transport. Thus, we demonstrate two critical components for building self-contained lab-on-a-chip devices.

This report presents a liquid-handling chip capable of executing metering, mixing, incubation, and wash procedures largely under the control of on-board pneumatic circuitry. The only required inputs are four static selection lines to choose between the four machine states, and one additional line for power. State selection is simple: constant application of vacuum to an input causes the device to execute one of its four liquid handling operations. Programmed control of 31 valves, including fast coordinated cycling for peristaltic pumping, is accomplished by pneumatic digital logic circuits built out of microfluidic valves and channels rather than electronics, eliminating the need for the off-chip control machinery that is typically required for integrated microfluidics.

Microfluidic technology is emerging as a useful tool for the study of brain slices, offering precise delivery of chemical factors along with robust oxygen and nutrient transport. However, continued reliance upon electrode-based physiological recording poses inherent limitations in terms of physical access as well as the number of sites that can be sampled simultaneously. In the present study, we combine a microfluidic laminar flow chamber with fast voltage-sensitive dye imaging and laser photostimulation via caged glutamate to map neural network activity across large cortical regions in living brain slices. We find that the closed microfluidic chamber results in greatly improved signal-to-noise performance for optical measurements of neural signaling. These optical tools are also leveraged to characterize laminar flow interfaces within the device, demonstrating a functional boundary width of less than 100 μm. Finally, we utilize this integrated platform to investigate the mechanism of signal propagation for spontaneous neural activity in the developing mouse hippocampus. Through the use of localized Ca2+ depletion, we provide evidence for Ca2+-dependent synaptic transmission.