Challenges and solutions to ultra-high-throughput screening assay miniaturization: submicroliter fluid handling

Inkjet printing for pharmaceutics – A review of research and manufacturing

“…An increasing library of potential molecules and a growing range of targets were leading to a rapidly growing series of assays. The pharmaceutical industry as a whole recognised the benefits of highly multiplexed and parallel analysis through large matrices of reacting units, driving a trend in moving from millilitre-scale work in test tubes to tens of microlitres in high density well-plates and ultra-high throughput techniques (Dunn and Feygin 2000) of sub-microlitre volumes. An early example of an industry-led cost-benefit analysis (Rose 1999) estimated the benefits of moving to higher density assays at USD156,000 per year for one assay equivalent to savings of USD5 million for 32 assays/year.…”

“…It is the second challenge for which inkjet printing was identified as a potentially important tool (Blanchard et al 1996, Lemmo et al 1997, Sittampalam et al 1997, Burbaum et al 1997, Lemmo et al 1998, Oldenburg et al 1998, Schena et al 1998, Rose 1999, Dunn and Feygin 2000, Bellavance et al 2000, Taylor et al 2002. The key features of inkjet that lend themselves to the liquid handling challenges of micro-array technologies are (i) noncontact deposition with a significant stand-off distance, ensuring that the size of the well is no longer limited by the size of the dosing nozzle, (ii) repeatability and accuracy of inkjet-deposited drops once their formation is optimised, (iii) accurate control of both individual drop volumes and total volumes by waveform and print signal controls, (iv) low reservoir volume requirements and (v) minimal space requirements for the system.…”

“…Microarrays for HTS are a necessary development in the next stage after combinatorial chemistry, to show the potential effectiveness of the library that has been built up. As laid out clearly by Burbaum et al 1997, the predicted throughput required to test 10 6 compounds against 200 targets would require a prohibitively expensive investment in compound and reagent manufacture without miniaturisation to ultra-high throughput techniques using sub micro-litre volumes (Dunn and Feygin 2000, Rodriguez-Devora 2012. These small volume regions can be within wells, or increasingly of interest, on flat surfaces with the drop localised to the printed region by barriers of poor wettability (Kudo et al 2007).…”

“…A recognised element of ensuring successful development of 'system discovery' techniques using inkjet printing (Figure 2(1)) is that of highly precise fluid handling (Dunn and Feygin 2000, Lemmo et al 1998, Rose 1999, Taylor et al 2002, Chai et al 2013. In inkjet printing the effect on a pharmaceutical agent must be considered during:…”

A microfluidic chip for controlled release of drugs from microcapsules

“…As we know, the widely used microtiter-plate-based high throughput analysis is basically approaching its physical limit, and also has the following limitations: [22][23][24] (i) it requires robots to operate; (ii) it consumes a large volume of agents and drugs, hence the whole process is expensive; (iii) it is still a relatively time-consuming process with relatively low throughput; (iv) the reagents are easily evaporated, especially for the 1 ll-volumes of 1536-well plates; (v) it is not convenient to monitor the effects of the combination of different potential drugs; and (vi) it is not easy to monitor the dynamic effects on cells by changing the drug dose, which requires the capability to control the drug release. In contrast, this droplet microfluidic platform essentially could address all the aforementioned issues, thereby paving a way for the controlled drug effect analysis with high throughput.…”