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BellBrook to Merge with Sister Firm Salus to Add Microfluidic Cell Assays to HTS Lineup

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BellBrook Labs, a provider of high-throughput screening assays, plans to merge with Salus Discovery, a startup formed last year by several BellBrook founders that is developing a microfluidic-based platform for cellular assays.
 
John Majer, chief operating officer at both BellBrook and Salus, told CBA News that BellBrook’s board of directors approved the merger this week. As a result, BellBrook will acquire a technology platform under development at Salus called the MicroConduit Array, or MCA, and the two-person R&D team at Salus will join BellBrook’s staff of 13 people.
 
The merger formalizes an already close relationship between the firms. BellBrook was founded by Majer and CEO Robert Lowery in 2002 with the intention of developing biochemical assays for the high-throughput screening market. However, Majer said, “We always talked about a better way of doing cell biology to more accurately replicate the conditions inside the body.”
 
Lowery eventually began working with David Beebe, a professor of biomedical engineering at the University of Wisconsin-Madison and an expert on microfluidic technology. Last year, Lowery, Beebe, and Majer launched Salus Discovery with the goal of commercializing the MCA technology for drug-discovery applications.
 
But it soon became clear that there was more overlap between the two firms than initially thought. “There was really a very tight collaboration between the companies — too tight to really draw a line between them,” Majer said. “It would have been impossible to sort out who owned the intellectual property, and administrative complications made it obvious that we needed to merge these companies.”
 
As a result, BellBrook will now round out its HTS product line with the MCA platform, which it hopes to launch by the middle of the year. The company plans to have prototype versions of the system ready in time for the Society for Biomolecular Sciences annual meeting next month, where Steven Hayes, principal scientist at BellBrook, will present a tutorial on the technology.
  
Hayes told CBA News that the MCA platform promises to overcome several limitations of traditional cell-based assays — namely, their inability to accurately represent the behavior of cells in vivo.
 
Currently, Hayes said, “cells are grown on flat plastic for an assay and they’re grown alone, sitting in a dish. The two ways to improve that would be to get the cells in a three-dimensional matrix, which is more representative of the tissue, and to give them [proximity to] the other cell types that they would be interacting with in the cell — the ultimate goal being to make more predictive drug-discovery assays.”
 
Hayes noted that even though there has been quite a bit of development both in three-dimensional cell matrices and in co-culturing different cell types, there has been little progress in overcoming both limitations at the same time, and in high-throughput.
 
The microfluidics platform offers an advantage, he said, because it allows BellBrook to design complex patterns of cells on each array. “We can create patterns of different cell compartments in different three-dimensional matrices, and try to get as representative as an in vivo situation as possible,” he said.
 
As an example, Hayes said that the Salus team has developed assays in which “breast carcinoma cells are embedded in a matrix representative of the basement membrane, and next to them is a compartment of fibroblasts, representing the stromal compartment.”
 
He noted that this configuration will result in a more biologically relevant assay than one performed with only breast cancer cells because the signaling between those two cell types plays a key role in tumorigenesis “and can alter the response of cells to cancer therapy.”
 
Hayes said that the “breakthrough” technology behind the platform is a concept called “passive pumping,” a method developed by Beebe that extends the MCA platform into the realm of high-throughput screening.
 
The method, which was awarded a patent this week (see Patent Watch, this issue), is based on a “simple observation,” Hayes said. “If you have a microchannel with holes or ports on either end, and if you put a small droplet on one side and a large droplet on the other, you will get pumping. The small droplet will pump into the channel, replace the fluid that’s in there, and the excess will go into the larger droplet.” 
 

“Every cell biologist we talk to sees new applications for this that we haven’t.”

The main benefit of passive pumping is that the system can run on any standard automated liquid handler, according to Hayes. In validation studies, the Salus team has put as many as 750 channels on a standard microtiter plate, he said. “We’re typically not working at that high a density, but the capability is there. And all you need to operate such a device is to place a relatively standard size droplet — in the 1 microliter to 8 microliter range — on these devices and let the passive pumping control the fluid flow.” 
 
The company claims that this capability will enable researchers to run assays with far fewer cells — a particular benefit in the area of primary cells, “where you don’t have a limitless pool,” Hayes said. “You only have so much from a given patient sample, and we can do a lot more assays on a given number of cells than in a typical well format.”
 
BellBrook has not yet delivered the system to any industry users — one of the primary reasons it hopes to have prototypes in hand for the SBS meeting.
 
Majer said that BellBrook plans to offer a custom design service in which it will develop MCA-based assays for particular customer applications, as well as a set of off-the-shelf MCA assays for common applications. Pricing for the system has not yet been determined.
 
Majer said that BellBrook sees an opportunity in leveraging its current HTS customer base of approximately 100 labs in order to jump-start MCA sales. “Most of those labs are also doing cell biology assays,” he said.
 
However, he noted, the potential applications for the platform are quite broad. “Every cell biologist we talk to sees new applications for this that we haven’t,” he said. “The ability to control and manipulate these cells is unparalleled by any other technology, so where this will end up being used is probably a whole lot of places.” He cited cell migration assays in biology labs to chemotherapy sensitivity response testing in the clinic as examples of the range of potential applications.
 
BellBrook intends to focus the platform on drug-discovery applications he said, but hopes to make the technology available to other markets through agreements with third-party suppliers.

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