Hoping to expand the capabilities of its RainStorm technology platform, RainDance Technologies last week launched the dScreen Consortium, a collaboration with Sanofi-Aventis’ high-throughput screening facility and the Université de Louis Pasteur, both located in Strasbourg, France.
The project has two primary objectives. First, it seeks to expand the range of applications for RainDance’s RainStorm technology beyond DNA sequence enrichment to quantitative, high-throughput compound screening using purified targets and cell-based assays, and measuring the dose-response curves for those compounds. Second, the consortium aims to take advantage of the fact that the RainStorm technology produces picoliter-size droplets to develop a new approach to compound storage in which compounds will be stored in droplets using a microfluidic device.
“To inventory compounds in plates requires a significant amount of infrastructure and logistic capabilities on the part of pharma companies to manage, literally, millions of compounds,” said Steve Becker, vice president of commercial operations for RainDance.
In the RainDance droplet format, scientists are working at the picoliter level, where they can put millions of droplets in a single tube. “So we can significantly reduce the footprint and the logistics requirements,” he said.
When the consortium achieves its objectives, RainStorm would be integrated into a common workflow for high-throughput screening, a component of which is a drug maker’s compound library, which can consist of hundreds of thousands to millions of compounds. The pharma industry would like to be able to interrogate those compound libraries with purified targets or cell-based targets.
“The idea is to have a high-throughput way of handling all of those compounds in picoliter-size droplets, and interrogating either cell-based targets or purified targets using the compound droplets,” said Michael Samuels, RainDance’s manager of protein and cell applications.
One of the key bottlenecks in currently used compound screening platforms is that, because of the number of compounds and data points that are required to interrogate those targets, single-point assays are often done in the primary screen.
“What our technology, because of its simplicity and speed, will allow us to do is develop dose-response curves for every compound in the initial screen,” Samuels said. “This is what we are developing with our partners in dScreen.”
“The idea is to have a high-throughput way of handling all of those compounds in picoliter-size droplets, and interrogating either cell-based targets or purified targets using the compound droplets.”
In the initial phase of the dScreen Consortium, the partners will begin to develop this microfluidic-screening system. For instance, Sanofi scientists will contribute their expertise in the screening area because the other partners have complementary experience in microfluidic engineering, droplet generation, and manipulating microdroplets.
“Our major role is to ensure that the objectives of the project and the progress of the project are such that at the end, we have a machine and a technology that we can use in an industrial screening setting,” said Martin Galvan, scientific director for Sanofi-Aventis’ research site.
He said that the next step is to define very precisely the objectives of the project for the next month, and the criteria for the go/no-go steps. Gavan said that Sanofi researchers will also work with the two other consortium partners to develop assays, data processing needs, et cetera.
The dScreen Consortium and RainDance’s European affiliate, RainDance France, will be housed within the Université de Louis Pasteur’s Institut Science et d’Ingénierie Supramoléculaires, where RainDance co-founder Andrew Griffiths has his lab.
Nicolas Carboni, general manager of the l’Association pour le Développement de la Filière Science de la Vie-Santé en Alsace, said that that Alsace-Biovalley’s role in dScreen was to bring Sanofi on board.
“We had recognized, with Andrew, the huge potential that that [the RainStorm] technology has for HTS,” Carboni said.
He said that when he pitched the idea of using the RainStrom technology, Sanofi’s initial reaction was less than enthusiastic. However, “When I presented them with some more information, they recognized very quickly that it would be a breakthrough, and that its potential value would be very important to them.”
Through that project and working with RainDance, Alsace-Biovalley also helped RainDance establish RainDance France in Strasbourg.
Carboni said that the regional government in Alsace and the French Agency for Innovation, or OSEO, are funding dScreen research at the Université de Louis Pasteur and RainDance. Sanofi is funding its own part of the project. The estimated cost of the project was not disclosed.
However, Carbioni said that in France, in general, when there is a collaborative agreement between private entities and public labs, ownership of any IP that is developed is shared.
Exclusive rights to develop the resulting IP is typically provided to the private company, though, when there is a full, exclusive license the private partner will manage the IP on behalf of the public university
The dScreen consortium is organized somewhat differently in that each partner will retain what is relevant to its core business. As a result, “RainDance will be marketing the results of the program in terms of the use of their technology for drug-screening purposes, Sanofi will retain its own results for its internal use, and in terms of the Alsace-Biovalley cluster, we will most likely develop a service platform based on the results of the program,” Carboni said.
RainDance claims that its RainStorm technology produces picoliter-volume droplets at a rate of 10 million per hour. Droplets are generated by infusing aqueous samples, such as cells, at a perpendicular angle to opposing oil streams.
Surfactants present in the oil stabilize the droplets while providing a biocompatible environment for the contents of the droplets. Droplets are loaded into microfluidic chips and spaced out within an oil stream at regular intervals for further processing.
Pairs of droplets are merged together in the presence of an electric field generated by electrodes embedded within the microfluidic chip. Droplets are sorted by the application of an electric field gradient to direct droplets to one of two collection streams. Sorting decisions are based on the product of a cell, enzyme, or chemical reaction within each droplet.