Combinatorial nanodroplet platform for screening antibiotic combinations

Abstract

We have developed a combinatorial nanodroplet platform for screening antibiotic combinations and successfully screened drug response of pairwise antibiotic combinations from selected antibiotics using the platform.

Facile and scalable tubing-free sample loading for droplet microfluidics

“…Of note, here we emphasized on sample loading and therefore generated only one droplet with a fixed reagent concentration per sample, but multiple droplets with various reagent concentrations can be readily achieved, as we demonstrated through food dyes (Fig. 3 ) and in our earlier works 41 , 42 , 44 , 47 . Upon in-line incubation and fluorescence detection, in the resulting fluorescence trace, we observed droplets with distinct FAM intensities that corresponded with the order of sample infusion (Fig.…”

Microfluidics for antibiotic susceptibility testing

“…Baraban et al used a system with 1000 media droplets of 100 nl each, each droplet being separated from its neighbor media droplets by a portion of mineral oil. This indexing of droplets in a piece of tubing is the same as in the earlier work of Boedicker et al 129 and later by Churski et al , 138 Postek et al , 130 and Li et al 131 Apart from establishing MIC with a fluorescence-based detector, Baraban et al measured the saturation number of bacteria per droplet volume, being 27 × 10 4 cells per 100 nl droplet for the conditions used. The authors showed that their platform is more precise than a gold standard platform for clinical AST, the VITEK® 2 by bioMérieux, 139 due to the large numbers of droplets screened per single experimental run.…”

“…A system similar to that of Postek et al 130 was presented recently with a different approach to droplet generation and emulsion handling. 131 Single-cell level studies have also been performed in droplets by Liu et al , 132 Lyu et al , 133 Scheler et al , 134 and Kaushik et al 135 Kaushik and colleagues manually (in a non-automated fashion) generated emulsions with different antibiotic concentrations and with single cells encapsulated in droplets, then measured end-point signals from droplets to establish whether the cells grew or not. Scheler et al run similar experiments, however, on a larger scale: to identify emulsions with different antibiotic concentrations after pooling the droplets, the authors color-coded them before pooling the droplets for incubation and detection.…”

Artificial intelligence-accelerated high-throughput screening of antibiotic combinations on a microfluidic combinatorial droplet system

“…to produce nanoscale to picoscale droplets, in which the target bacteria are encapsulated along with antibiotic combinations. [22][23][24][25][26][27][28][29] Since the passive method does not require external energy such as electric field, magnetic field, acoustic field, etc. to generate droplets, it is safer and easier to use than the active approaches and therefore has been extensively applied in combinatorial drug screenings.…”