Frances Ligler tells Kathleen Too about portable, automated biosensors for fast, on-site detection of pathogens, toxins, pollutants, drugs and explosives

	Frances Ligler is a senior scientist at the US Naval Research Laboratory's Center for Bio/Molecular Science and Engineering. She has been the recipient of numerous medals and awards including the Women in Science and Engineering Outstanding Achievement in Science Award.

How did you come to work for the US Naval Research Laboratory?
Joel Schnur, the current director of the Center for Bio/Molecular Science and Engineering, was starting an interdisciplinary department studying the self-assembly of biomolecules. I thought this was an interesting vision and I wanted to work at the molecular level; I could see that this was where breakthroughs were happening. So I joined Joel and, after a year, started the programmes in biosensors, trying to make functional molecules on surfaces and using optical readout systems.

As a senior scientist, you spend your time starting new programmes and providing scientific leadership without a large management or administration load - so I can be senior and do science all the time. I have six or seven post docs at any one time, but generally, I work with other staff members to form a group around a particular project. The type of work I do is so interdisciplinary that it takes engineers, chemists and biologists, and occasionally a physicist, to do it all, so we put our expertise into a number of projects.

Tell us about the biodetection systems you designed. How long does it take to develop the technology, from having the idea to commercialising the device?

The 'Raptor' is a fibre optic biosensor that has four optical fibres with four different functions in a 12 pound box. The system is fully automated; all the user has to do is put in the sample and press run, and the result is given in ten minutes. Alternatively, it can be attached to an air sampler and left out in the field to send results at pre-programmed time intervals.

The 'Biohawk' has a sensor that is a third of the size of the 'Raptor'. It has eight fibres with eight different functions. The air sampler is integrated into a backpack, so collection of bacteria or toxins from the air, for example, can be done by someone wandering through the field operating the device from the backpack.

Both systems detect mostly biological warfare agents; they have been used in tests for anthrax at a post office. They have also been used for detecting bacteria and toxins in foods, and detecting E. Coli and other indicators of sewage contamination on beaches and in the Great Lakes.

We started working on these ideas in 1986; the very first fibre optics were available in 1997 and the first automated systems were available in 2000. But they didn't really become reliable systems until around 2003. That is a pretty typical path.

The whole process requires a lot of paperwork. The technology that we transferred for drugs of abuse detection in saliva went through all the Food and Drug Administration clinical approval processes. The system that we used for the detection of explosives in soil and groundwater went through the Environmental Protection Agency, where it got draft approval. You have to be willing to go through all the paperwork to prove the technology to the regulatory agencies that are responsible for that kind of testing.

You put your biology expertise to excellent use by using on-chip and microarray technologies to detect multiple targets. How easy to use and stable are these devices?
If you immobilise proteins very carefully, their function is not jeopardised. If you dehydrate them in the presence of a protective agent, that prevents denaturation, so you can keep them at room temperature for two years and continue to reuse them. They are pretty robust. There are other, even more robust molecules you can use as recognition molecules, such as the small molecules in low molecular weight antimicrobial reagents. Work being done by Ellen Goldman, George Anderson and others looks at small single-chain antibodies that are so robust, you can heat them to 90 degrees Celsius and they continue to work. You can put them in organic solvents to remove unbound material, and rehydrate them, and they will still work. Molecules like that will further extend the stability and reliability of the systems for long-term use by non-technical users.

What is the ideal sensor for a non-expert to use?
The equivalent of a pregnancy test. The problem is that you can't usually get the sensitivity you want for multiple applications, and the amount of sample that you can actually test is limited. But these devices are ideal in that they are low cost, and you can see the results with your own eyes. So, the easier we can make a device to use in terms of limiting the complexities of the fluidics [the use of a fluid to perform analog or digital operations] and the read-out, the closer we get to something being broadly applicable.

Biosensors can be used in many areas. Where do you see the applications being the most valuable and cost effective?
The two most immediate ones are clinical testing and food monitoring and testing; they are both very powerful for on-site clinical analysis.

What does the future hold for biosensor research?

I think biosensors will be a lot more user-friendly, and plastic optics will have an important part to play in making the optics cheaper and smaller. Right now, the optics are the most expensive part of the system, so if you can make those cheaper by integrating the optics and the fluidics, so much the better. I think plastic optics will be easier to integrate than trying to make the fluidics in silicon.

We are going to learn about disease markers such as cancer and other infection biomarkers. I think that will be a real breakthrough for casualty care or care of patients with infectious diseases or heart attacks, for example. I think that is going to be a pretty big market.

Another medical market that will be important is learning which markers are important for the application of different drugs as a form of personalised medicine. I think we need to be further down the road with this before it is accepted by the medical community.

If you weren't a scientist, what would you do?
That's easy: I would raise Arabian horses and do pottery. I ride a lot and do 50-mile endurance races on my horses.