A Plug-and-Play, Drug-on-Pillar Platform for Combination Drug Screening Implemented by Microfluidic Adaptive Printing

Abstract

Traditional high-throughput drug combination screening requires automatic pipetting of drugs into high density microtiter plates. Here, a drug-on-pillar platform is proposed for efficient combination drug screening. Using the proposed approach, combination drug screening can be carried out in a plug-and-play manner, allowing for high-throughput screening of large permutations of drug combinations at various concentrations, such that drug dispensing and cell-based screening can be temporally separated, and therefore can potentially be performed at distant laboratories. The dispensing is implemented using our recently developed microfluidic pneumatic printing platform, which features a low-cost disposable cartridge that minimizes cross contamination. Moreover, our previously developed drug nanoformulation method with amphiphilic telodendrimers has been utilized to maintain drug stability in a dry form, allowing for convenient drug storage, shipping, and subsequent rehydration. Combining the above features, we have implemented a 1260-spot drug combination array to study the effect of paired drugs against MDA-MB-231 triple negative human breast cancer cells. This study supports the feasibility of the drug-on-pillar platform for combination drug screening and has provided valuable insight in drug combination efficacy against breast cancer.

Anti-Cancer Drug Screening with Microfluidic Technology

“…Li et al fabricated a plug-and-play, drug-on-pillar platform for combination drug screening using a microfluidic pneumatic drug printing platform [63]. They nano formulated chemotherapeutic drugs, which are more stable for storage, shipping, and subsequent rehydration [64].…”

Combinatorial nanodroplet platform for screening antibiotic combinations

“…[49][50][51][52][53][54][55] By incorporating advances in liquid handling techniques, such as inkjet printing, contact printing, and acoustic ejection, drug screening is realized by combining reagents in a step-by-step manner that enables a high degree of freedom for reagent combinations and allows for multistep screening reactions. [56][57][58][59][60][61][62][63][64] Alternatively, nano/ pico-liter droplet techniques hold great potentials for combinatorial screening since multiple reagents can be readily configured in a droplet and droplet systems typically allow high scalability testing. [65][66][67][68][69][70][71][72] However, these techniques do not fully meet the needs for combinatorial antibiotic screening, which requires on-demand combination conditions with little reagent consumption, automated screening procedures at high throughput, and easy data analysis and interpretation.…”

Telodendrimers: Promising Architectural Polymers for Drug Delivery

“…As the general chemical methodologies involved in the synthesis of telodendrimers were becoming available, the biological perspective of their applications became the next focus [ 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 ]. As noted by Newkome in 1985, it was the search for an architectural outline with the ability to form micelles that inspired the scientific community about these hybrid structures.…”