In the last of our four part series with Dmitry Kashanin, we look at the work that has been done since Cellix took on the challenge of working with impedance. Many people are aware of the Coulter Counter, the first medical device to take measurements with impedance. But it was a simple blood cell counter. How has impedance technology changed since then?
Dmitry:
“Obviously a Coulter Counter is just a very primitive impedance measurement device. It was primarily used for counting cells and particles, not identifying one cell from another. It typically used a low frequency impedance measurement and just measured if a cell passed the electrode.
Now you can measure several frequencies at a time. This is purely due to developments in the electronics that make it capable of multiprocessing. FPGA technology has allowed us to process several signals at a time meaning we can use two, four or six different frequencies if we want to and probe different properties of the cells.
"In the last 2 years we have increased the throughput of our tech by a factor of 10. As far as we are aware, no other groups have made these kinds of developments."
Also, as a result of being able to go to higher frequencies of excitation, you can shrink down the size of the device and measure smaller things. Now we can measure down to bacteria in 30 micron channels with 20 micron electrodes.
Another big innovation in impedance is learning how to control the position and orientation of cells passing through the microfluidic channel. We’re applying this in several different applications now to measure cells and debris more precisely.
I think our biggest contribution to the development of modern impedance is the speed. We now have cells running at m/s through the measurement channel. We can analyse very close to the whole cytometry at 10,000 cells/s. A few years ago this was only available at flow rates around 10-100 cells/s. We developed this high speed impedance in the last few years solely through better electronics.
Additionally, our sorting capability itself is not trivial. We have developed droplet sorting which requires electrical charging on chip to be integrated into the whole impedance detection system. It is common to charge cells in sorting, but our developments to downsize and make the tech work on a chip was a big achievement for us!
In the last 2 years we have increased the throughput of our tech by a factor of 10. As far as we are aware, no other groups have made these kinds of developments. We usually see a flow rate of 30-50 microlitre/min in other groups but we’re sitting at 300-500 microlitre/min.
In terms of clinical application, throughput was the big limiting factor. You need an exceptionally high flow of cells per second to be able to work with the amount of cellular material that might make a difference to a patient. At Cellix, we are now coming to a point where we are starting to directly compete with flow cytometry. Of course it’s not as advanced in terms of labelling receptors but there are many other applications, for example, viability testing, where you don’t need such precision but you do need the throughput.
I think our progress is really important. Even 2 years ago, I was not sure that it would be possible. I knew in theory what throughput should have been possible but getting there was another thing! It’s something we’ve achieved that we think is going to make a big difference.
It really feels now that our future goals for impedance cytometry is more in applications. We are looking for applications that could utilise the technology, putting it into devices and integrating it into systems. It can be easily multiplexed, it’s electronics based, it’s robust technology that can have a lot of different uses. Also, it’s just smaller and you don’t need a high precision setup of optics and lasers. It’s just a chip with electronics and fluidics. Before long it’ll be a handheld device.”
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