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MIT Technology Sorts Cells By Whole- or Sub-Cellular Events

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Investigators at the Massachusetts Institute of Technology have developed a microfluidic cell-sorting device that combines microscopy with facile, image-based sorting. The device contains a microwell array that can be passively loaded with mammalian cells and subsequently studied using microscopy.
 
The force of an infrared laser can be used to levitate cells of interest from their wells into a flow field for collection. The researchers’ work will be published as the cover story in the Dec. 15 issue of Analytical Chemistry, and appeared online last month. 
 
The authors — Joseph Kovac, a graduate student in MIT’s department of electrical engineering and computer science, and Joel Voldman, an associate professor in the department — were able to demonstrate image-based cell-sorting predicated on both whole-cell and localized fluorescence.
 
They reported that they achieved post-sort purities of up to 89 percent and up to 155-fold enrichment of target cells.
 
According to Kovac and Voldman, their technology is very scalable and supports 10,000 individually addressable trap sites. They said that the technique can be used to sort large populations of cells based on subcellular spatio-temporal information. This is either difficult or impossible with currently available sorting techniques such as fluorescence-activated cell sorting, they said.
 
Voldman, who has previously spoken with CBA News (see CBA News 6/1/07), provided an update on his work and his laboratory’s future plans. 
 

 
Could you tell me a little about how this technology works?
 
It’s a very simple idea that you take a glass slide that has wells in it. You flow cells onto the slide and they fall into the wells. The slide sits on a standard microscope, and you do your assay, imaging, or whatever it is you are going to do.
 
When you want to select out wells, the technology comprises an automated microscope that goes to those sites where the cells are in those little wells, and the laser acts as a fire hose to kick those cells up and out of the wells. A sideways flow pushes the cells off the chip to be collected.
 
How can the cells be levitated with light?
 
Light has a force associated with it. It is not a lot of force, but it is enough, because the cells weigh so little. It’s actually pretty simple to do. The laser used is fairly inexpensive. You just shine it up and it will levitate the cell.
 
At what point are you in this project?
 
We have made these 10,000-site arrays and we have sorted cells. We have been able to image cells and sort them based upon the localization of fluorescence. That is something that you could not do with fluorescence-activated cell sorting.
 
We are now looking at doing a couple of things. Cell retrieval is currently somewhat manual, just because we were more focused on the actual sorting and injection of cells in this first manuscript. We are developing ways to make the cell retrieval a little more elegant.
 
We are also looking at a few different applications, in terms of what we want to use the technology for next. We want to consult with various people such as basic scientists and those in the pharmaceutical industry. We want to ask them, “Imagine if your signal is encoded in how fast something is happening or where it is happening, rather than just providing a ‘yes’ or ‘no,’ ‘there’ or ‘not there’ answer. What would you do differently?”
 
I think that is something that no one has thought about. You develop your assays based on the existing technology, so when you open your mind up to think about what you may do differently, that is the process that we are going through.
 
Do you have any timetable for this project?
 
The valves are actually pretty straightforward. Its not a new technology necessarily, its silicon valves are vacuum-activated. We have some new chips that have the valving structure just to test those out. That should not take more than a few months to do.
 
Do you have any plans for further publications?
 
Yes, but we are not certain when, or in what journals. It depends on the results of the assays.
 
Are you planning on having beta testers for this technology?  
 

The technology is not very complicated. If someone is technically savvy, we could probably help them set it up in a matter of days. Initially, it is probably easier to have people come to us to try something out to see if it has a chance of working, rather than us distributing the technology.

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