Grad Students Le Zhen, Fanghui Ren, and Jing Yang use a Ramen spectrophotometer

Grad students Le Zhen (ChE), Fanghui Ren (ECE) and Jing Yang (ECE) use a Raman spectrophotometer with a microscope to focus a laser on optical biosensors. 

Biosensor technology is used to detect a wide variety of substances — from drugs, to cancer biomarkers, to chemical contaminants in our food and drinking water. Diatoms — tiny, single-celled plants found in water all over the planet — are playing a big role in a new type of biosensor being developed by Alan Wang at Oregon State. The new technology has a high selectivity and sensitivity, and is much less expensive than traditional methods of detection. 


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Transcript

KEITH HAUTALA: Hey there, podcast listeners! We’re trying out a new format this season of Engineering Out Loud. Instead of putting two related stories in a longer podcast, we’re going to create some shorter podcasts that feature just one story. So, let us know what you think. Email us at engineeringoutloud@oregonstate.edu or leave us a note on our Facebook page at Engineering Out Loud. Now, on with the show.

Welcome to another episode of Engineering Out Loud. Today, we continue our discussion of engineering for human and environmental health with a look at a new type of biosensor technology that can cheaply and quickly detect a wide range of potentially harmful substances — things like contaminants in food and drinking water, explosives, dangerous drugs, even chemical warfare agents.

The unsung heroes of this new technology are single-celled organisms from the ocean, called diatoms. They’re a type of algae, and they already play a couple of important roles in the maintenance of life on Earth. They create oxygen through photosynthesis, and they serve as the base of the entire food chain for our whole planet. Here’s Alan Wang, professor of electrical engineering and computer science here at Oregon State.

ALAN WANG: It’s the smallest photosynthetic plant on our planet. Actually they are very abundant in water, including seawater and freshwater, and they produce about 50 percent of the oxygen we breathe in the atmosphere, and also produce about 40 percent of the carbohydrate compounds on our planet. So, basically that’s the base of the food chain of all our planet.

HAUTALA: It’s estimated that there are over 100,000 different species of diatoms, and they come in a bewildering array of different shapes and colors. They’re fascinating to look at under a microscope. But what makes diatoms interesting to researchers like Alan are their porous, glasslike shells, or skeletons, which have some interesting and useful physical and optical properties.

WANG: Diatoms very unique creatures, because they have a kind of periodic, porous skeletons which are made of biosilica. Basically, diatoms take the minerals from water and then they assemble it into their shells to create the skeletons. And the unique thing about this skeleton is it has periodic structure which can reflect resonant light in the visible wavelength range. You can use these unique optical properties for many interesting engineering applications.

HAUTALA: Alan is interested in using light to detect specific molecules by measuring the way photons bounce off of them using something called Raman scattering. We’ll delve more into that in just a minute. But, as it turns out, the unique light-enhancing properties of the diatom skeletons make them particularly well suited to this purpose.

WANG: So, basically, we found that the periodic structure of the skeleton can enhance the light. You can think of it as a light-trapping structure, which can enhance the optical field so that you can increase the sensitivity to detect many different chemical and biological molecules.

HAUTALA: I asked Alan what goes into designing a good general-purpose biosensor, and here’s what he had to say.

WANG: For biosensors, if you consider performance, the two most important things you need to consider, the first is selectivity. The second is sensitivity. So, selectivity, basically you want to detect the molecules of one (type) within the presence of many other molecules, because they will interfere with each other. So the easiest way is to separate them, and then you can detect it. For example, chemists have worked using chromatography to separate molecules and then use mass spectroscopy to detect them. So we are you a similar strategy. So basically we put the diatoms as a thin film on a glass substrate — it’s a porous substrate. If you put the mixed samples onto the porous film, they’ll basically diffuse and then that can separate the molecules along the different paths, and then you can use optical methods to detect the different molecules at different the spots.

HAUTALA: You might remember doing an experiment in chemistry class where you put a piece of blotter paper into a vial of liquid and watch as different colors separate out while the liquid climbs up the paper. That’s sort of similar to how this thin, porous film of diatom skeletons works to separate different types of molecules. The fancy scientific name for that is thin-film chromatography.

WANG: So that’s the separation capability provided by diatoms which you can achieve. That’s the selectivity you want. And the second thing is sensitivity. So diatoms have a very unique, periodic structure — we call it a photonic crystal.

HAUTALA: Photonic crystals? That sounds like something out of Star Trek.

WANG: Actually, nature is very abundant with photonic crystals. For example, if you look at the wing of a butterfly, there are very fancy colors of blue and green. Actually, the colors are coming from the periodic air holes of the butterfly wings. So, if you look at the wing under SEM, you’ll see the periodic structure. So they basically reflect the light at a certain frequency. So any periodic structures — like opal, the wing of a butterfly, or the feather of a peacock — they all naturally possess a photonic crystal structure. So, they have the structure that can reflect the light at certain frequencies. So, it’s called a photonic crystal. And, of course, diatoms, which I mentioned just now, it’s also a photonic crystal. Because if you look at the diatom under a microscope, people found they are different colors. So, they’re simply reflecting the light in a different way.

HAUTALA: That’s where Raman scattering comes in. Now, if you didn’t study a lot of physics, you might think this has something to do with ramen noodles. It doesn’t. I asked Alan if he could explain it to someone like me.

WANG: Yes. It’s a kind of optical testing method. So, you can think if you have a laser as a probing light, you shine it on the molecules. So, the molecule will absorb the light and sometimes produce a photon with a different energy, so at a different wavelength. This is called Raman scattering. We can use this as a signature to identify and detect different molecules. So, people have demonstrated a single molecule — and including my group — we have demonstrated the detection of a single molecule using surface-enhanced Raman scattering. So, basically, we can achieve ultra-high sensitivity from the diatom platform as well.

HAUTALA: So, if this Raman scattering spectrum is like a fingerprint for a specific type of molecule, I wanted to know: Does every molecule on the planet have its own unique Raman spectrum?

WANG: Many molecules have the spectrum signature, but not every one. Some molecules don’t, like water. Water doesn’t have too much of a Raman spectrum. That’s good, because water is the most abundant background molecule. So if water has a Raman signature it will bury all the signal you have. So water doesn’t have too much Raman signal, but of course some other molecules don’t have Raman spectrum as well. But many molecules we are interested in, like drugs, explosives, and the toxic antibiotics, they have the unique Raman spectrum.

HAUTALA: Now, if you have any familiarity with analytical chemistry, what Alan’s doing with diatoms and Raman scattering sounds a lot like what analytical chemists do in laboratories around the world using time-tested techniques like high-performance liquid chromatography (that’s HPLC to its friends) or gas chromatography/mass spectrometry (GC/MS). But Alan says that his diatom-based biosensor has many advantages over these techniques.

WANG: They are bulky equipment that can be only used in laboratories, so we have to take the sample and go back to the lab and do the analysis. It is time-consuming and expensive, but our technology is based on thin-film chromatography and surface-enhanced Raman scattering, so we can do it on site. It’s just a single chip, with a portable Raman spectrometer, so you can inspect and analyze these chemicals on site within like 10 minutes, and also consume very little amount of power. And also the cost per test is much lower compared with HPLC or GC/MS. So I wouldn’t say that it will replace GC/MS or HPLC every place, but at least for portable sensing for on-site detection or point-of-care detection, I believe our technology has a much higher advantage.

HAUTALA: Alan’s team was recently awarded a grant from the U.S. Department of Agriculture to develop a biosensor to detect food contaminants. Specifically, they are working to develop technology to detect prohibited aquaculture drugs, such as antibiotics, in imported seafood.

WANG: Those antibiotics are prohibited in the U.S., but since much of our seafood is imported from Asia, we need to inspect the seafood. But the problem is inspecting the seafood is very time-consuming and expensive. So, only like a few percent of the seafood imported to the U.S. is inspected. The majority is not insepected simply due to the cost. So, imagine if we can have a rapid, easy-to-use and low-cost technology, we can have a very fast inspection. So it will significantly enhance our food safety.

HAUTALA: Aquaculture antibiotics aren’t the only illicit drugs that this technology can detect. These diatom-based biosensors can also pick up traces of substances like cocaine or marijuana.

WANG: Those illicit drugs can regularly be found from the user in the urine or the blood. But detecting them at a high sensitivity and low cost is still a challenge. So, right now people are still reliant on HPLC or GC/MS for detection. If we can develop a portable sensing technology, so you can detect it on site — even by just law enforcement on site — and then it will find very broad applications for medical care, law enforcement, and forensics.

HAUTALA: And the potential doesn’t end there. From health care to law enforcement to food safety, these biosensors can be used to detect just about anything, anywhere.

WANG: I wouldn’t say that it can detect everything, but it does detect a broad spectrum of different target molecules. So we have proved that you can detect the biomarkers for diseases like cancer, and also we can detect contaminants in food and drinking water, and also detect explosive molecules like TNT.

HAUTALA: OK. So we can say that diatom-based biosensing is a versatile technology with potential applications in a variety of different fields that currently rely on offsite lab testing. And, in addition to being faster and more portable than HPLC and GC/MS, the diatom technology has another key advantage over these techniques: The equipment costs are lower. Much, much lower.

WANG: If you look at the sensor system, it contains two parts. One is the equipment that you use to acquire the optical signal. The other is a sensor chip, that you can separate the samples. OK? So, for the equipment, optical equipment, it’s already commercially available. And, right now, we are testing a portable Raman spectrometer with our diatom sensor. So we are not working on the equipment; we are working on the sensor. So, once the sensor is mature, because the commercial equipment is there already, it may cost about $10,000 to $20,000 for the equipment. It seems expensive, but when you compare it with GC/MS or HPLC, it is still like 10 times cheaper than those for the equipment. So those are affordable equipment that that can be used for many applications.

HAUTALA: On a per test basis, it turns out that diatom-based biosensors are more economical than current lab methods as well.

WANG: Our target is to make the sensor costs below one dollar per chip. So, then it’s definitely affordable. Because if you consider GC/MS or HPLC, they have a chromatography rod that may cost $1,000 dollars. And it’s reusable, but you maybe can reuse it like 10 times or 20 times. If you consider the total cost divided by the times it can be reused, it’s still much more expensive than the diatom-based, although it’s a one-time disposable.

HAUTALA: I want to thank Alan Wang for talking with us today. This episode was produced by me, Keith Hautala, along with Rachel Robertson, Steve Frandzel, and Mariah Reddington. Don’t forget to visit our website, engineeringoutloud.oregonstate.edu, for bonus content and full show notes. Our intro music is “The Ether Bunny” by Eyes Closed Audio on Soundcloud. All songs and sound effects are used with permission under a Creative Commons license. Links to all songs and sound effects and their licenses can be found on our website.