'LIGHTSABR' – portable drug discovery system

RESEARCHERS are using microbeads to miniaturise a high-throughput drug discovery process from a large-scale laboratory process to a bench-top device.

Current high-throughput screening systems analyse the biological activities of samples. They typically occupy 900 m² of space or more, use high volumes of the samples, and have operational costs that range in millions of dollars.

The process relies on robotic devices that retrieve samples from a chemical library, as to not allow any contamination of the samples. They place samples into an 'assay microplate,' which measures each compound's biological activity – for example, whether the compound inhibits a particular enzyme involved in viral replication.

The cost and size of the systems have prevented such screening libraries to exist outside large research facilities and pharmaceutical companies. The team’s innovation will allow the volumes of the process to be scaled-down by a factor of 100,000, opening up the process for smaller-scale research projects.

The team from The Scripps Research Institute (TSRI) in Florida, US, has used samples of individual compounds which are chemically attached to a microbead, which suspends a small liquid volume of the sample. The microbeads are built on the “microfludics principles” similar to the film used in fluid suspension hoppers in an inkjet printer.

The microbead is placed into the miniaturised screening device called LIGHTSABR (Light-Induced and Graduated High-Throughput Screening After Bead Release) which uses a variable UV-light emitter to cleave the sample free of the microbead. Once the sample is free it can undergo assay testing.

The team’s innovation is that the technique allows users to vary the UV illumination to adjust the amount of a compound cleaved from the microbead and adjust the dose of the compound being tested. The team demonstrated the dosing function by using an assay designed to find inhibitors of HIV-1 protease, a key enzyme involved in the replication of the virus that causes AIDS.

Alexander Price, senior research associate at TSRI, said, “It is possible to generate a library of millions of compounds in a week for about US$500.”

The team had to calibrate the UV emitter and the concentrations of the samples precisely in order to achieve the same results as the large-scale process.

Price added, “Hundreds of laboratories around the world could operate their own miniaturised screening facilities, using their own assays to go after targets that are of most interest to them.”

The next step the team will take is to apply the microfluidic LIGHTSABR to the laboratory's DNA library to classify existing antiviral compounds, and pursue new antibiotics and other drugs that address the emergence of resistance in evolving pathogens.

Analytical Chemistry. DOI: 10.1021/acs.analchem.5b04811