Abstract
Droplet microfluidic technology is becoming increasingly useful for high-throughput and high-sensitivity detection of biological and biochemical reactions. Most current droplet devices function by passively discretizing a single sample subject to a homogeneous or random reagent/reaction condition into tens of thousands of picoliter-volume droplets for analysis. Despite their apparent advantages in speed and throughput, these droplet devices inherently lack the capability to customize the contents of droplets in order to test a single sample against multiple reagent conditions or multiple samples against multiple reagents. In order to incorporate such combinatorial capability into droplet platforms, we have developed the fully Integrated Programmable Picodroplet Assembler. Our platform is capable of generating customized picoliter-volume droplet groups from nanoliter-volume plugs which are assembled in situ on demand. By employing a combination of microvalves and flow-focusing-based discretization, our platform can be used to precisely control the content and volume of generated nanoliter-volume plugs, and thereafter the content and the effective dynamic range of picoliter-volume droplets. Furthermore, we can use a single integrated device for continuously generating, incubating, and detecting multiple distinct droplet groups. The device successfully marries the precise control and on-demand capability of microvalve-based platforms with the sensitivity and throughput of picoliter droplet platforms in a fully automated monolithic device. The device ultimately will find important applications in single-cell and single-molecule analyses.
Highlights
1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction Droplet microfluidics has recently emerged as an attractive technological platform for high-throughput and high-sensitivity biochemical analysis[1,2,3] with applications ranging from drug screening[4,5], directed evolution[6], antibody screening[7], and protein crystallization[8], to disease genotyping[9,10] and antibiotic susceptibility testing (AST)[11,12,13]
This burgeoning interest in droplet microfluidics can be attributed to its many advantages
A fully integrated droplet platform capable of achieving combinatorial analysis remains in high demand
Summary
Droplet microfluidics has recently emerged as an attractive technological platform for high-throughput and high-sensitivity biochemical analysis[1,2,3] with applications ranging from drug screening[4,5], directed evolution[6], antibody screening[7], and protein crystallization[8], to disease genotyping[9,10] and antibiotic susceptibility testing (AST)[11,12,13]. Droplet digital PCR platforms have become a turnkey tool for quantitative detection of rare biomarkers such as genetic mutations[9], detection of each additional target via droplet digital PCR would require an additional device or complex optical indexing schemes[9,17,18,19,20] Methods such as picoinjection[21,22,23] and droplet merging[24,25] represent early attempts toward achieving combinatorial analysis within a single droplet device by adding a single reagent at a single concentration into droplets. In a more recent demonstration, Chang et al developed a flow-focusing-based droplet generation device with programmable pneumatic valves that produced droplets with custom contents[27] As this device functioned merely as a droplet generator, this platform necessitated user intervention to transport each droplet group off-chip for incubation and detection in a “fragmented” workflow. A fully integrated droplet platform capable of achieving combinatorial analysis remains in high demand
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
