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MIT Team Develops Image-Based Cytometer That Marries Microscopy, Automated Sorting

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Joel Voldman, an associate professor of electrical engineering at MIT, wanted to be able to sort cells based on the information available from microscopy, such as cellular morphology, intracellular fluorescence, and cellular dynamics.
 
So he and a team of colleagues developed a cytometer that combined microscopy with automated sorting.
 
The technology uses reversible and addressable “traps” to hold single cells in place to enable researchers to observe them. The technology, which uses dielectrophoresis to transiently hold the cells in place until they attach to the substrate, is designed to then release selected cells either by turning off electrodes at specific sites or by using a laser at specific sites to push cells out of the well for sorting.
 
According to Voldman, once the cells are released, researchers can perform cell-based assays on them. The team’s cytometer, which is a passive chip that fits under a fluorescent microscope, then sorts the selected cells.
 
Cell-Based Assay News spoke with Voldman this week about the technology.   
 
Can you give me a little background on how you developed this technology?
 
What we have wanted to do for the last several years is develop a way to do image-based cell sorting. We wanted to take these fantastic technologies that look at proteins with available imaging modalities and microscopy, and add the ability to sort on top of that.
 
We have taken a number of different technological approaches to doing the same thing. One of our guiding principles is to come up with something that minimizes disturbance to biologists’ workflow as it exists right now and is as inexpensive as possible.
 
One of our assumptions is that most, or at least an increasing number, of labs will have automated microscopes at their disposal. What can we add to that to do the sorting part of their experiments?
 
We thought about making either chips that we think of as ‘active cover slips,’ or taking an optical approach that comes in and plugs into the optical path on the microscope.
 
We are not trying to replace someone’s microscope; we are trying to add functionality to it with as minimal a disturbance as possible.
 
Do you feel that this technology has potential for commercialization?  
 
I do, but I’m always a little hesitant because I am not a marketing person. Academics will tell you all sorts of things, some of which may be true.
 
Do I believe there is a market for this? Yes. Have I formally evaluated this market? No.
 
But whenever I talk to biologists and tell them what we are trying to do, there is a lot of excitement. I think that our approach of not trying to build a multi-hundred-thousand-dollar instrument, but trying to build something that may sell in the ten-thousand-dollar range that plugs into what you already have decreases the barrier to market entry and increases the market size. The instrument becomes an add-on to your existing scope.
 
What niche in the cellular-analysis market do you think that this technology would fill?
 
I would imagine that any research lab, whether academic or pharma, that has a microscopy setup and is in the business of either understanding fundamental cell biology, in terms of signaling networks, or that is involved in screening of molecules for potential therapeutics, would be interested in this. Basically, this would include anyone who has developed a way to look at their phenotype of interest.   
 
The analogy I use is that flow cytometry has been a fantastic technology, and I doubt that when people developed it way back when, they had any inkling of the kinds of things that researchers would make this technology do in order to serve their own ends.
 
We are trying to add that sorting to microscopy, and while we have things that we want to do with it, I think that it will widely applicable.
 
You are in the fourth year of a five-year RO1 grant. What are your future plans for this technology?
 
We have learned a lot in the time that we have been doing this. In some sense, we have broadened ourselves into looking at a few different ways of tackling the problem. I like to think that we are somewhat technology agnostic in that if there is something that I want to do, I really do not care how I do it, as long as it meets certain requirements.
 
One path will certainly be to pursue further funding from the NIH to move the instrument further along in its development.
 

We are now at the point where we are ready to start talking to instrument-development companies, to see what feedback we get. We have actually had some preliminary discussions and the feedback is positive. However, as we go from showing figures and drawings of things to showing photos and images, we can have more concrete discussions with these companies. 

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