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Lights, Camera, Assay: Reify Turns Imaging Tech Toward High-Throughput Cell Measurement

This article is the second 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.

NEW YORK, Dec. 30 (GenomeWeb News) - If you want to phenotype a person, you can take their pulse and blood pressure at one time point, and get a static snapshot of their vital signs. But you can also follow the person around all day and observe the dynamics of that person's routine to get a more in-depth picture.

Mark Foster, CEO of Cambridge, Mass.-based startup Reify, uses this analogy to explain the concept behind his company's high-throughput cellular assay technology, the Visible Discovery Platform. The system, he said, enables users to see "how biology changes over time."  Its high-resolution video cameras rapidly scan 384- or 96-well plates of cellular assays from above and capture images of these cells many times per second. They then selectively deliver these images to an off-the-shelf computer system that processes the cells' measurements.

While most automated cellular imaging systems consist of "a microscope on an x-y stage," said Arman Garakani, Reify's chief technology officer, "we have developed a parallel design capture system which allows us to go back to the same cell within a second or two, and allows us to sample the dynamic nature of the cell according to its own modality."

The company has spent nearly two years developing the technology with seed financing that Foster and Garakani mostly put up themselves, and it's now working to raise an additional $5 to $7 million in a Series A round of financing. So far, a lead investor has already jumped in, Foster said, and the company hopes to close the financing round within the next few months. Reify is also at work on signing partnerships with big pharma and biotech; According to Foster, the company has gotten into proof-of-principle stage with "a lead adopter pharma company in Cambridge" for its high-throughput cellular migration assays. The company is also touting its high-throughput muscle contraction and protein translocation assays.

But the eight-person startup faces a daunting level of competition in its bid for pharma cellular assay business. Foster himself lists Cellomics (see story  12-05-03), Atto Biosciences, Compucyte, and Amersham as competitors in the instrumentation arena, and he sees Cytokinetics, Kalypsis, Acadia, and Atugen as rivals who also use cell-based assay platforms as part of their drug discovery services or partnership offerings.

Foster nevertheless believes that the company can distinguish itself by the way it combines its capabilities to measure cells and implements these into assays. "We are the only company out there that's taking the dynamic piece of cell measurement seriously enough that we have designed a novel approach to capture and measure that dynamic," he said.

The company's not-so-secret weapon appears to be Garakani, a computer vision and signal processing engineer who spent 15 years at machine vision instrumentation maker Cognex before leaving to found Reify, and who has 12 patents to his name. Garakani has designed the cameras in the system to capture images with a frame-rate that adjusts to the motion of the cells underneath them, and reacts to the cells rather than simply scanning over them in a pre-programmed pattern. "The capture times are a second or two between the frames, and the quantification is the same," he said. "The machine keeps a dossier on every cell," which is "a totality of all the motion vectors that [are in] the body of the cell. ... The measurements are numbers (for example microns per second for instant velocity) over time as well as statistics, such as average instant velocity among all cells over time or average instant velocity for a given cell over time, etc. From these measurements other statistics may also be derived. Parts or all of the video can also be re-processed to extract newly defined measurements," Garakani said. The informatics component, Phenomica, currently runs on Mac OSX but can be transferred over to Linux or Windows.

So far, the company has published one patent application for this system, No. 20030185450, entitled "Method and apparatus for acquisition, compression, and characterization of spatiotemporal signals." The application, filed Feb. 13, covers methods and apparatus to measure and quantify "dynamic processes" through assessing a spatiotemporal signal for self similarity.

While biologists have been taking measurements from cells for decades, the Reify system is designed to capture this information from large numbers of cells in a parallel automated fashion, and integrate the data so that pharma can rapidly cycle through assays to validate targets or eliminate them through predictive toxicology screening.

"If you look at the choke points in drug discovery today--target validation, secondary screening and lead optimization, and predictive toxicology, unlike target identification and primary screening, which have been nicely automated by the genomics revolution and high-throughput biochemistry- the common denominator is that biology is slow, its's noisy, and there needs to be a better way to bring it" to the next level, Foster said. "That's the big problem that we are trying to address with our company."