Researchers at the Massachusetts Institute of Technology have combined a 30-year-old technology with modern microchip design and manufacturing to develop a tool that can manipulate cells on the surface of a silicon wafer.
Matthew Lang, an assistant professor of biological engineering and mechanical engineering at MIT, and David Appleyard, a graduate student in biological engineering, have identified a way to use optical tweezers, which harness the force from a laser’s light beam, to manipulate objects such as cells on opaque silicon wafers.
Their work was published online on Oct. 10 in Lab on a Chip.
Optical tweezers are usually used on a glass surface inside a microscope to enable researchers to observe the movement and exact position of very small objects.
According to Lang and Appleyard, the tools are able to work on silicon wafers that are opaque because silicon is transparent to infrared light, which a laser can easily produce.
To develop the system, Appleyard and Lang tested discarded wafers donated by other MIT researchers to determine what thickness and surface texture worked best for their purposes. They then tested the system with different cell types and microbeads.
To demonstrate their system’s versatility, Appleyard said they set it up to collect and hold 16 Escherichia coli cells at once on a microchip and manipulate them to form the letters “MIT.”
Lang and Appleyard spoke with CBA News this week about their future plans for the technology and its potential application in drug discovery.
Can give me a little background on this technology?
Matthew Lang: The technology is actually fairly old, having been developed over 30 years ago. It is referred to as ‘optical trapping’ or ‘optical tweezers.’ It’s the main technique used in single-molecule biophysics.
Largely, the technique is used by those who build their own microscopes and their own instruments. We are one of those labs. We were excited about probing the biological inorganic silicon interface. So we went and built an instrument that can use this technique, this technology, through these silicon wafers.
David probably built three of these in different iterations to pull it off. It is not an obvious thing. If you look at a normal glass slide, you can see through it. It’s a good substrate for doing microscopy, but if you look at a silicon wafer, it’s nontransparent to visible light, so there are all these hurdles to implementing a technology that is normally used with transparent slides onto this new environment.
How did you and David refine this older technology that has been around for 30 years or so?
David Appleyard: I think our main innovation was refining the instrumentation to take these measurements and manipulate objects using the older optical trapping technology, and mapping this technology to a new substrate, so that it can work for silicon wafers and other semiconductor devices.
ML: Our initial goal in this was just taking these measurements at the biological inorganic interface, but as we started to play around with the technology, we thought…there may be a lot of other neat applications of this instrumentation. Can we use it as a construction device or a tool to allow us to build something on a wafer?
And these things are not really our lab’s mainstay, so we just wanted to show that this potential existed with the technique, and hopefully, do our part in enabling other scientists to take this idea and run with it in some other directions.
You said that many people were using this technique in their work on neurons. Can this technique be used with other types of cells that involve electrical impulses such as cardiac or skeletal muscle?
ML: Certainly. The optical tweezers can be used to pick up pretty much any type of cell. I do not know of a cell type that it cannot pick up.
DA: There are a lot of things in terms of disease diagnostics in which you could envision coupling the exquisite sensors you find on microchips with the ability to deliver a cell to these precise locations and use it for things like disease diagnostics or drug discovery.
How could this technology be applied to drug discovery?
ML: I saw a talk recently about patch-clamping. This technique has similar technical hurdles in terms of the instrumentation that is involved. There are many parallels with optical trapping.
Researchers have figured out a way to use these two technologies in parallel. You can just envision, now that it is possible to trap multiple particles simultaneously through silicon wafers, there would be parallels with looking at optical trapping for doing drug discovery in the silicon microchip environment.
Is this something that you plan to commercialize?
DA: I do not know of any immediate plans. We would love to [collaborate] with groups that would be interested in these applications. I guess we are going after our immediate goals of trying to probe at the molecular level this biological-inorganic interface.
But having those kinds of funding streams looking for commercial application would be a huge benefit for enabling the continued development of this technology.