ac4006414_si_001.pdf (1.65 MB)
Sequential Operation Droplet Array: An Automated Microfluidic Platform for Picoliter-Scale Liquid Handling, Analysis, and Screening
journal contribution
posted on 2013-07-16, 00:00 authored by Ying Zhu, Yun-Xia Zhang, Long-Fei Cai, Qun FangThis contribution describes a sequential
operation droplet array
(SODA) system, a fully automated droplet-based microfluidic system
capable of performing picoliter-scale liquid manipulation, analysis,
and screening. The SODA system was built using a tapered capillary-syringe
pump module and a two-dimensional (2D) oil-covered droplet array installed
on an x–y–z translation stage. With
the system, we developed a novel picoliter-scale droplet depositing
technique for forming a 2D picoliter-droplet array. On this basis,
an automated droplet manipulation method with picoliter precision
was established using the programmable combination of the capillary-based
liquid aspirating–depositing and the moving of the oil-covered
droplet array, the so-called “aspirating–depositing–moving”
(ADM) method. Differing from the previously reported droplet systems
based on microchips, microcapillaries, or digital microfluidics, this
method can achieve complete and flexible droplet manipulations, including
droplet assembling, generation, indexing, transferring, splitting,
and fusion in the picoliter range, endowing the present system with
ultralow sample/reagent consumptions and substantial versatility in
analysis and screening for multiple different samples. To demonstrate
its feasibility and versatility, we applied the SODA system in multiple
experiments required in drug screening, including the screening of
inhibitors for capases-1 from a chemical library, the measurement
of IC50 values for the identified inhibitors, and the screening
of the synergistic effect of multiple inhibitors. In the experiments,
the consumptions of samples and reagents are only 60–180 pL
for each droplet microreactor, which are commonly 3–5 orders
of magnitude lower than those of conventional multiwell plate systems,
and 1–2 orders of magnitude lower than other droplet-based
microfluidic systems for multiple sample screening. The ability of
the SODA system in performing complicated and multistep droplet manipulations
was further demonstrated in the serial dilution of nanoliter-scale
inhibitor droplets with concentrations spanning 6 orders of magnitude
for IC50 profiling, which includes droplet generation,
indexing, splitting, transferring, and fusion with picoliter precision.