At A Glance
Lisa Monaco, deputy director, Marshall Space Flight Center Group Science Directorate; project scientist, Lab-on-a-chip application development; bioscience and engineering team lead.
Experience: 2001-present - Jacobs Sverdrup Technology, Huntsville, Ala.
2000-2001 — Project Scientist, Iterative Biological Crystallization, Huntsville, Ala.
1999-2000 — System Engineering and Support, Mevatec, Huntsville, Ala.
1993-1995 — Research Associate, University of Alabama, Huntsville, Center for Microgravity and Materials Research.
1988-1992 — Graduate Research Assistant, University of Alabama in Huntsville, Center for Microgravity and Materials Research.
Education:1992 - PhD, Materials Science, University of Alabama in Huntsville,
1990 - MS, Chemistry, University of Alabama in Huntsville,
1985 - BS, Biology, Seton Hill College.
Lisa Monaco, a project scientist working for a contractor with the Marshall Space Flight Center in Huntsville, Ala., has been involved with space science research and development since US National Aeronautics and Space Administration fellowships supported her graduate school studies at the University of Alabama-Huntsville.
Today, she works in an interdisciplinary team of engineers and scientists in a facility on the Marshall Space Flight Center grounds, with access to the nearby US Army Redstone Arsenal’s MEMS fabrication facility. The team, called LOCAD, is four years into work, performed in collaboration with the Carnegie Institution and Caliper, to develop lab-on-a-chip technology for applications in space.
BioArray News caught up with Monaco to discuss the challenges of taking this terrestrial technology and developing it to the point where it might ride on a Mars rover sometime 10 years from now to analyze the planet for signs of life.
How did you first get involved in lab-on-a-chip technology?
It was about four years ago. I had been involved with a small team put together to optimize a researcher’s time on the space station to do protein crystal growth. What you lack on the space station is your set of beakers, and your ability to just pick and choose what you want and to mix them in whatever ratio. To really emulate what researchers did on the ground and to be effective up there for three months, you really wanted to give them the opportunity to set up experiments, monitor, and then change their conditions, change their proportions of buffer-to-protein solution, and there was nothing up there to enable you to do that. So as the project scientist for this team, we started to look at ways of mixing small volumes because we really wanted to entice the pharma industry. When they are talking about hot targets, they are talking about very limited sample material. So instead of using the old hardware that has been going up on the shuttle, and on the space station, we wanted to let them use small volumes. Doing a web search, I came across Caliper. We kept our eyes on them. As soon we as got engineers on board, about a year into the project, I said, ‘Hey look, there’s ink jet printing, there’s lab on a chip, there’s small miniaturized pump systems.’ So they went off and did their trade studies. And, at that time, I had assembled about 12 experts from all over the world in crystal growth. I had people from Bristol Myers Squibb, Schering Plough, and some of the cancer institutes. I had them come in every six months and evaluate the concepts that we were working on. Lab on a chip by far blew away the other concepts. You have to keep in mind too that we are going into space, so we need to worry about things like generating waste — forget pipette tips. We don’t want to have to be flushing tube lines, and have dead volumes involved. Contamination is an issue, volumes of materials, all those things that you need to look at when you are designing something for space. Lab on a chip just seemed to really stand out as the best approach. So we almost immediately formed a collaboration with Caliper and we set about coming up with requirements. First of all, we did an initial study, using the chips they already had to see if we could grow crystals, and we did that probably a little over three years ago now, and then we went about designing a chip for protein crystal growth. That’s a chip that Caliper produces for us.
How do you go from protein crystallization to biosensing on Mars?
So, that is a couple of years ago. We are sitting here and, of course, NASA headquarters starts to reevaluate the science that is going on the space station. Protein crystal growth is no longer a priority. About that same time, when we were working with this lab on a chip stuff and we had procured one of Caliper’s application development units, the Caliper 42, a work station specifically for developing chip working concepts. There are not many that exist outside of Caliper, maybe a handful or two. We are still using it today. It has a fluorescence arm on it; you can manipulate pressure at various ports on this chip; or you can move fluids electrokinetically.
So, here at Marshall, we have an advanced life support system that has water loops, they have a need for monitoring water quality, and of course, there is a need for crew diagnostics, and microbial detection. We just brainstormed and came up with about 30 other areas that we thought NASA might be able to use this technology for. We started to call all around to the different NASA centers and talk with folks in some of those areas to see if they had an interest. So what we have today as a result of that are collaborations on anything from planetary protection, to life detection on Mars, to crew health diagnostics. For the past year and a half we have been focusing on those items. In the meantime, the president has this new vision. Well, everything we were doing was along that path, and it was really fortuitous for us that it turns out that now some of the emphasis is on exploration, which is essentially where we have been now for over a year and half.
One of the issues about lab-on-a-chip technology is the issue of getting things in and out of it.
Yes, that’s the macro-to-micro interface. Right now, Norm Wainright, who is at the marine biological lab, has a portable test system that is handheld. His chip can detect gram negative microbes in about 10 minutes. His cartridge slips into the test system, a unit about the size of my phone. Our project (Lab on a chip development) is trying to take a unit like that and make chips to go in it. Then, we will try to move along the path of miniaturizing and automation as well. It’s funny you brought that up. Everybody says ‘I can do this, I can do that, my sensitivity is great,’ but it seems like everybody is ignoring the sample handling, the sample preparation. That is one thing that our collaborators at the Carnegie Institution are helping us address. We are breadboarding with them some hardware that we hope will help us to integrate onto a Mars rover to look for biomarkers, for evidence of past and present life on Mars.
In looking at the instrumentation lists of the current Mars Rovers, there are no biosensors on board.
The first rovers up there have no life detection whatsoever. There is a mission coming up in 2013, which we are striving to get involved with.
What are the technical challenges for doing that?
It’s a big list. We call it: the things that keep me up at night. I know we have a certain dimension for the Mars rover and I’m going to say it’s not much bigger than two bricks. We would like to do six chips at time, maybe five times and run maybe a dozen or two dozen chips. The radiation experience going past the Van Allen belt is something to concern ourselves with. If we are doing microarray work, anything we print on needs to have a shelf life that will accommodate that kind of mission. Sensitivity is an issue. Another issue is making sure that whatever you detect is not something from the people who were handling it at the JPL before launch. Another technology issue is that you are going to have a piece of Mars rock, and somehow you are going to have to be looking for minute, impossibly low concentrations of markers in a sample, and it has to get from a piece of rock all the way to something that is a soluble, that possibly has go over a microarray.
What are the probe strategies you might use?
You might be looking for antihopanes, a long carbonaceous molecule you typically find when you might have had past life, so you might lay down an antihopane antibody.
Would nucleotides be affected by space?
I have heard people say there is no way that you can keep this intact. That is why shielding is important. We will be looking for ways to shield our microarrays. No one has actually done it. That’s definitely on our task list.
What about miniaturization?
How low does it need to go? People talk a lot about nanotechnology. Great. Now I have something I can’t see unless I’m using a scanning electron microscope. That is why we are taking a progressive approach. Right now, if you see what they are using on station, what they have to unload just to do water sampling, or microbial detection — they are still swabbing and growing cultures, and looking five days later. What we plan on doing in the next year and a half, is taking this unit from Charles River and flying it on-station because there are just basic questions that haven’t been answered like: Does the pathogenicity of this microbe change in a microgravity environment, or in a higher radiation environment? We are hoping to put something even in a handheld level in the hands of astronauts so we can start to do things quicker, more efficiently. Of course, crew time is an incredibly big constraint right now, as well as up-mass. So, I would say that at no time in NASA’s history has miniaturization been as important, as our shuttles will not fly until the next scheduled launch date.