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German Startup Zellkraftwerk Launches Chip Cytometry Service; Aims to Release Instrument this Fall

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German cytometry startup Zellkraftwerk has begun offering researchers early access to its Chipcytometry platform in advance of a planned fall sales release for the device.

The company launched the platform this month as a biomarker development service aimed at academic researchers and pharmaceutical firms, Christian Hennig, Zellkraftwerk's co-founder and CEO, told ProteoMonitor. It intends to begin sales of the instrument itself in September, he added.

The company's Chipcytometry platform was originally developed by researchers including Hennig at Hannover Medical School, and has to date been used in biomarker discovery collaborations with institutions including MD Anderson Cancer Center, the German Competence Network on Multiple Sclerosis, the German Center for Lung Research, and Radboud University.

The platform works by fixing and immobilizing target cells in microfluidic chips where they are stained with an antibody to a protein marker of interest. The marker is then detected via automated epifluorescence microscopy. The sample can then be bleached and stained with an antibody to another marker for multiplexed biomarker detection. The cells can be stored for up to 16 months, allowing for iterative analysis of protein markers.

The platform, Hennig said, is not a direct competitor to techniques like conventional flow cytometry or the newer CyTOF mass cytometry platform offered by DVS Sciences. Rather, he suggested, it enables a somewhat different set of cytometry experiments.

Specifically, it allows researchers to investigate protein biomarkers repeatedly and over an extended period of time, capabilities that could prove particularly useful for discovery experiments and work with small sample sizes.

"If I have a lot of cells – say a cell line or mice where I can sacrifice a lot of mice – and I can repeat and repeat and repeat my experiment and I have marker sets that are fixed, then I would always prefer to use flow cytometry," Hennig said. "But if you have very precious samples... and you want to play around – try this marker, try this marker, try this marker – then I would use chip cytometry."

"In flow cytometry, you have one shot with your fixed marker sets, and then, if it's gone, it's gone," he said.

This can prove particularly challenging for researchers interested in hard-to-obtain cell types, Jan Detmers, Zellkraftwerk's project manager of clinical testing, told ProteoMonitor.

"For example, if you want to work with [cerebrospinal fluid], with flow cytometry there is a minimum number of cells you need to get into the flow in order to get a readable result ... and so far flow cytometry on [central nervous system] diseases has been really difficult," he said. "Because chip cytometry is not sacrificing the cells, you can work with much lower cell numbers."

In a 2008 paper by Hennig and his colleagues in the journal Cytometry introducing the technique, the authors wrote that they were able to obtain a 10-fold improvement in sensitivity compared to conventional flow cytometry. The platform also offers a significant jump in multiplexing. While flow cytometry typically maxes out at around 20 markers due to overlaps in the emission spectra of the fluorophores used for such assays, the Zellkraftwerk researchers have multiplexed as many as 51 markers using the Chipcytometry platform and, Hennig said, can in theory go significantly higher.

There are limitations associated with the system's multiplexing process, however. Most notably, because the markers are measured iteratively, with a separate staining, imaging, and bleaching cycle for each marker, the process is relatively slow, with each cycle taking around 15 minutes for a sample size of around 20,000 cells. Flow cytometers, on the other hand, measure around 20,000 cells per second, while mass cytometry tops out around 1,000 per second.

In an email to ProteoMonitor, Bernd Bodenmiller, a researcher at the University of Zurich who extensively uses DVS Sciences' CyTOF mass cytometry machine for single-cell proteomics, questioned also if these repeated steps might lead to difficulty with the "accumulation of artifacts that increase with every cycle."

Hennig, said, however, that the platform controls for fluorescence remaining after the bleaching process. It also controls for cell autofluorescence, he said.

In general, Bodenmiller said, the chip cytometry approach "is smart and has lots of potential," although he suggested more work was still needed to optimize the platform.

Like Hennig and Detmers, he suggested that it might find an "immediate niche... in cases where the cell numbers are very limited, in which every cell counts but many parameters should be measured." He cited analysis of circulating tumor cells as one example of such an application.

In addition to launching services using the platform and prepping it for the fall release, the company is in the process of developing a robotics system for use with the instrument, Hennig said.

This will prove key for increasing the system's throughput. While Zellkraftwerk can currently process around 400 samples a week in house, the manual version of the instrument slated for release in the fall can process only around 20 samples per week. The company plans to release an automated version of the instrument in the fall of 2014 that will up that to around 400 per week.

Currently, each chip can capture a maximum of 100,000 cells, and the platform can record data on a maximum of 50,000 cells.

Zellkraftwerk is planning a demonstration day in March where interested researchers can use a prototype of the system to analyze their own samples.

Detmers said the company expects to price the platform at around $150,000 when it goes on sale this fall, with the chips used in the analysis running around $20 apiece.

Zellkraftwerk, which formally launched in November, currently has seven employees and is funded by a €2.5 million ($3.3 million) grant from the German government that runs through 2014. According to Hennig, the company has no immediate plans to raise additional funds.

"The first priority, now that we've launched the [system as a] service for academic customers, is launching the service for drug-development companies, and then the next step will be to launch the instrument in September of this year," he said. "Funding questions will be on the agenda in 2014, maybe."

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