This article is the sixth in a series of bi-weekly columns focusing on the area of "high-throughput biology," or new techniques for high-volume cell-based screening and imaging that biopharma is using to validate targets generated through genomics or proteomics, screen for toxicity, and replace other traditional assays. Links to previous columns in this series can be found below.
NEW YORK, Feb. 24 (GenomeWeb News) - Labcyte is taking a high-tech, no-touch approach to handling nano-volumes of liquid for cell-based assays.
The Sunnyvale, Calif., company -- which sprang from the November 2003 merger of Labcyte LLC and Picoliter --recently displayed a beta version of its Echo 550 "touchless" nanoliter liquid handling instrument at the Lab Automation 2004 conference in San Jose, Calif., earlier this month.
Rather than pipette tips or pins, the machine uses focused sound energy to transfer as little as 5 nanoliters of sample at a time from one microplate to another.
"We generate sound with a transducer, then it runs through a focusing element, which is much like an optical lens," explained Rich Ellson, the company's founder and chief technology officer. "If we can get that focal point for the sound to be close to the surface of a liquid; [then] project that focus from underneath the well plate ... and up through the liquid that's in the well to the surface, [we can] cause the drop to essentially jump off the top of the liquid and fly towards the target."
While the target for these jumping droplets could be anything -- a low-density microarray slide, for example -- in the case of the Echo 550, the target is an inverted microwell plate -- a feature that allows users to use the machine as a "compound reformatter," going from larger to smaller precise volumes of fluid without having to do dilutions or lose fluid with pipette tips.
Beyond just saving money and materials, said Ellson, the no-touch instrument can be used to solve a key problem in the process of doing high-throughput cell-based assays: the need to use the universal solvent dimethyl sulfoxide (DMSO) to dissolve the numerous compounds being tested, at a level that is not toxic to the cell.
While DMSO is the most common solvent that dissolves numerous compounds, one cannot "put a high concentration [of DMSO] into a cellular assay without distorting the assay, for in most cases it increases the permeability of cells," he said. "So what [pharma researchers] want to do is have a really small amount of DMSO but still have a large amount of the drug."
Lab technicians would be able to handle this through a set of dilution steps of the DMSO, but "as soon as you do [a dilution step] you would have the risk that your compound along the way somewhere precipitated and is actually sitting on the bottom of the second row of dilutions you are doing and never gets into the assay," said Roeland Papen, the director of marketing, who joined the company from Cellomics.
This Echo 550 has gone out to a single alpha customer, Amgen, and is now in beta testing with other customers the company said it could not name. Mostly, the customers are testing the system for compatibility with their different lab robot systems, Ellson said. The system is designed to "partner" with other lab automation components, and since it doesn't have any bulky tips or pins itself, this is relatively easy. But there are still details to work out. "What happens if somebody's robot slams into our plate gripper 50,000 times? These are the kinds of things you hear back from alphas and betas," said Ellson.
After further testing, Labcyte plans to fully launch the system commercially in June. (Orders can be taken now, but the product will not ship until June, Ellson said.) The basic system, without additional optional features, is priced at $225,000.
In addition to compound reformatting for cell-based assays and other compound screening, Labcyte is looking into applications for its sound-based liquid handling technology in proteomics, especially high-throughput transfer of proteomics spotting buffers. "We can serve that market very well," Ellson said. Protein crystallization is another potential application, although it requires more transfer of fluid.
Additionally, Ellson said some pharmas are interested in using the system's acoustic capabilities to manage their compound libraries. The system has the ability "to go in while the plates are sealed and determine how much of each fluid there is and determine how much is in these wells." This way, solutions with compounds that are precipitated or hydrolyzed can be eliminated prior to screening.
This instrument will be the latest addition to a line of more traditional liquid-handling products, including automated pipetting workstations and microplate washers, that the Labcyte LLC arm of the company contributed in the merger. While the Picoliter arm had IP and the hardware behind the Echo 550, the Labcyte arm also has provided an established sales organization for its products. "On the people side, one wishes that all mergers could be this good," Ellson said. "We're an R&D engineering organization ... and they were largely a sales and distribution organization."
For the merged group with 40-something employees, the upcoming launch of the Echo 550 will be the first test as to whether the organization can work as an integrated whole. It will also be a litmus test of whether nanoliter liquid-handling technology will be as marketable to pharma as plain-old pipetters.
Amersham Biosciences has signed an agreement with Guava Technologies to distribute the company's Personal Cell Analysis systems, along with its reagents and software modules, in Japan, Guava said today.
The Guava Technologies systems are micro-capillary-based instruments that allow users to analyze and count single cells using small volumes of sample, the companies said.
The systems are available in three configurations -- Guava PCA, PCA-96, and PCA-96 AFP (auto-fluorescent protein) -- and come with reagents and accompanying software. PCA is the smallest instrument, designed for manual, single-sample analysis in a microcentrifuge tube. PCA-96 and PCA-96 AFP systems perform the same cell analysis in an automated fashion on 96-well microplates and multiple microcentrifuge tubes.
This three-year exclusive agreement signals Amersham's increased investment in the cellular analysis market. The company, which is slated to be acquired by GE in the coming months, also offers a number of cellular assays and fluorescent reagents as well as its In Cell imaging analysis system and Leadseeker CCD imaging system.
For Guava, a privately held startup based in Hayward, Calif., this is its first major commercial distribution deal. The company, which was founded in 1998 just closed on its $27 million series D round of financing in December, solely on the development of benchtop cellular analysis systems, reagents, and software, according to its website.
Guava introduced its PCA-96 analyzers in 2003, and said in January that it had installed "hundreds" of the PCA systems at customers, including the top 20 pharma and top 10 biotech companies, as well as the NIH and other government labs.
Other High-Throughput Biology Columns: