Swedish cell-based assay company Cellectricon announced last week that it has raised SEK 53 million (about $7 million) in its Series B financing round, and indicated that it plans to use this funding primarily to launch Dynaflow, its microfluidics tool for high-content cell-based screening, in the US.
This funding will also go towards further development of the company’s next-generation microfluidics tool for high-throughput primary screening, according to Cellectricon’s CEO, Jakob Lindberg. Participants in the investment round included InnovationsCapital, Investor Growth Capital, and Karolinska Investment Fund. This round brings total investments in the company to SEK 99.6 million (about $13.4 million) since its inception in 2000.
Lindberg said Cellectricon has “three legs” to its functional cell-based assay business. “We have the DynaFlow leg … we have what is tentatively named the ElectroFlow leg, which is using capillary electroporation as a method of introducing … molecules into living cells (see story in this issue: Will Molecular Devices' Acquisition of Axon Affect Cellectricon?), and then we have a leg where we look at microfabricated structures for primary ion channel screening, which is a highly competitive field right now.”
The DynaFlow product, however, is the company’s current principal focus. Cellectricon is targeting this product at the biotechnology and pharmaceutical companies as a tool for increasing throughput and content in live-cell ion-channel drug screening for lead optimization.
“[DynaFlow] is basically a biochip to be used in conjunction with traditional patch clamp, but increases the throughput by roughly 2 to 100 times depending on the application,” Lindberg said. “It’s more for lead optimization. It enhances the data from traditional patch clamping.”
The aspect of the DynaFlow responsible for these claims is its patented microfluidic delivery system, which is based on laminar flow. This phenomenon typically is reported in small channels or tubes, according to Lindberg.
“What we detected was that if all these tubes or channels run in parallel with very thin walls between them, and then they just run out into an open channel, you retain laminar flow for quite a distance beyond the outlets in the open volume,” Lindberg said.
What this enables, said Lindberg, is a “barcode,” in the open fluid volume comprising 16 distinct chemical landscapes. One can then use a computer-controlled stage to move a patch-clamped cell at the end of a pipette across the different chemical environments, “almost at the level of digital switching,” he said.
Such a setup would offer an increase in throughput that would allow researchers to rapidly test several compounds in succession against a cell. But the increase in data quality, while not immediately apparent, is just as significant, according to Lindberg, especially as it pertains to ion channel screening.
“An ion channel can switch between an open and closed state within milliseconds, and sometimes faster,” he said. “Also, an ion channel desensitizes very fast — it gives an initial response, and then almost immediately stops giving a response.”
The consequence of this in a macrofluid environment, such as a well plate, is that researchers often don’t know what concentration hit the cell in the end, because the ion channel reacts so quickly. Also, desensitization means that the ion channel might no longer respond even in the presence of a compound that might otherwise have an effect on it.
The DynaFlow addresses that problem with the rapid switching environment, Lindberg said. “We can expose a cell to a ligand, and then we can enter a buffer stream immediately afterwards and avoid desensitization.”
The platform also allows one cell at a time to be exposed to different environments and subsequently analyzed, as compared to traditional screening, where a researcher might have to switch cells and run the risk of inconsistent gene expression from cell to cell, the company said.
“It’s a lot of small things, but when you add them up, it changes the data quality significantly,” Lindberg said.
The platform, which costs about $25,000 to $35,000, is already being used at big pharmas AstraZeneca, Merck, and GlaxoSmithKline, according to Lindberg, presumably in those companies’ screening programs outside the US.
“It was just launched in October, and we now need to take that launch globally,” Lindberg said in response to a question about how the recent funding would be used. “We have our first real road show in the US in June.”
Part of the Series B funding will also be used to further develop Cellectricon’s next-generation microfluidics system, which is intended to better enable primary screening along with lead optimization screening. Tentatively called NanoFlow, the system is slated to use the same technology as the DynaFlow, but with a few major adjustments: More than 16 channels, a dedicated system for driving fluid through the chip, and integrated software.
Current competitors to Cellectricon’s products include the PatchXpress automated patch clamp device from Axon Instruments and the IonWorks high-throughput electrophysiology system from Molecular Devices. (MD will soon add the PatchXpress to its portfolio due to its pending acquisition of Axon [see Inside Bioassays, 4/20/2004]).
But Lindberg said he sees Cellectricon’s technology as being more symbiotic to those platforms than competitive with them.
“If you look at the screening process, you go from primary screening to [the type of screening] in a lead optimization study,” Lindberg said. “In primary screening, you basically want a yes or no answer with very high throughput and low cost per data point. In lead optimization, you want extremely high information content, with good dose-response curves, very advanced kinetic studies … and you’re willing to pay easily 20 to 30 dollars per data point, from 10 cents in primary screening.”
IonWorks and PatchXpress are stuck in the middle somewhere, Lindberg added. “They have OK data quality, but not good,” he said. “They can barely do a dose response … and they have a fairly high cost per data point. However, the systems are automated, which is a big plus. But from a specifications standpoint, they are a bit wobbly.”
Lindberg knows, however, that these instruments do certain things exceptionally well, and hopes that one of their manufacturers, or a similar biotechnology company, will see the benefit of supplementing their instrument with Cellectricon’s talent for microfluidics.
“Those systems can crank out hits and early leads roughly from the secondary screening process, but those need to go through the lead optimization stage — and suddenly we have an advantage,” he said. “The NanoFlow will be able to take care of those hits and leads, and we then benefit from their systems, because that will result in more screening studies.”
“But we don’t intend to build the machines,” he added. “We see that Axon and Molecular Devices have beautiful automated systems when it comes to robotics, data management, et cetera. However, their microfabricated components, or actual interfaces to the cell, lack several dimensions, and that is where we are good.”
Cellectricon is aiming to talk to possible partners by the end of this year, but first the company has to gain a thorough understanding of the intellectual property issues in this area, Lindberg said.