Researchers at Johns Hopkins University have developed a microincubator for cell culture by integrating silicon microchip technology with microfluidics. The incubator’s microchannels, which rely on electronics to keep the cells within a specified narrow temperature range, are made of a soft silicon polymer so that cells and nutrients can easily be inserted and guided through the system.
In addition, the microincubator is made of a transparent material so that scientists can view the cells through a microscope or camera equipment without disruption of optimized cell culture conditions.
Jennifer Blain Christen, a postdoctoral fellow at Johns Hopkins University’s Whiting School of Engineering, spent the last three years developing the device as the focus of her doctoral thesis.
Christen and her doctoral advisor, Andreas Andreou, a professor of engineering at the university, published their work in the March 2007 issue of the Institute of Electrical and Electronics Engineers’ Transactions on Biomedical Systems.
Christen spoke with CBA News this week about the technology and how she is continuing to develop it.
Can you give me a little background on your work and how you identified the need for a microincubator?
I started out trying to do some very-large-scale integration design for studying cell-cell interactions. My colleagues and I found that a major obstacle to our work was an inability to grow cells on top of a chip and then interact electrically with the chip.
My background is in electrical engineering. A lot of what I started out doing was basic circuit design for microchips. We wanted to design different circuits to take measurements of cells or to do temperature-based reactions.
Unfortunately, we had a real issue in that we could not put electronics into an incubator. We also were not able to put all of our assessment equipment into an incubator.
Experiments where we wanted to take data on cells posed the problem of just being able to do the interface, in terms of having cells right there and being able to electrically contact them. We also faced the problem of being able to contact the cells continuously while keeping them alive.
So what really started this work was trying to have a good platform for continuously contacting the cells while maintaining their viability. I think of the work that we published as a kind of canvas for being able to do a lot of different things with electronics and interfacing directly with cells.
If I wanted to design a microchip that had, for instance, something that created or detected electric fields for pacing cardiac cells or being able to do a patch clamp, those kinds of electronics directly touching the cells is something that people do not normally do.
What I have created is a way for researchers to grow cells directly on a microchip and keep the cells alive over the entire cell cycle.
How does the technology work?
What I have designed into the chip on which the cells are growing is a heat sensor and a temperature sensor. As cells are sitting out in a regular environment, the temperature is constantly changing as people walk by. In addition, when researchers put something under a microscope to examine it, the temperature will increase by 15 degrees Celsius or so.
This device is something that continually updates the temperature. Its not like the way your thermostat at home works by coming on and off as needed to adjust the temperature to a specified level. This is something that always keeps the temperature of the cells right within plus or minus one degree Celsius of 37 degrees. You can also set the appropriate temperature for the cell line you are working with.
The nice thing about the chip is that the continual measurement and update cycle is going on. We also have the microfluidics built into the system because you have to have the medium for the cells. The system was designed with channels to introduce the adhesion factor into the system and a different set of channels to introduce the cells. We used fibronectin as the adhesion factor but it really does not matter.
By having separate channels, you do not have cells that get stuck in the microfluidic channels, as you do in other systems.
The other nice thing is that the system is three-dimensional, which totally eliminates the shear stress problem from the microfluidics because the fluid is coming in from a raised channel, the fluid drops down and comes in from an axial direction, rather than shear, as in other systems that you’ll see.
What is the next step in this work?
Now that we have something where we can put a microchip together with the cells, I am working on a couple of different things. One of the things I am working on is a system where you can do optical measurements while you keep your cells alive.
I think in the article it mentions using a light conduit to take images of the cells. The first thing we are doing is some simple GFP experiments to look at whether we can do transfections and things like that.
We are going to put the imaging technology directly into the system, so that users do not need a big external camera or things like that. This is a self-contained system and it has the incubation and everything right there; users are not locked into using one device. They are free to use our system with any kind of instrumentation they want. We can build a lot of capabilities into the system.
Another thing I am doing is building some sensors into the chip. In addition to just measuring temperature, we want to measure other properties of the cell while they grow. For example, we could measure oxygen concentration, CO2 concentration, and other things that are important for cell growth.
Is this something that you plan to commercialize?
We have not pursued that actually. I finished my PhD in May and in the meantime, have been looking for academic positions. So we have not yet pursued the commercial aspect of the technology at this point.