In this 21st Century Chemist profile, Purdue University analytical chemist Mary Wirth works with "nanomaterials" to improve the clarity and accuracy of tests for tiny "biomarker" proteins that indicate disease -- specifically, levels of PSAs, or Prostate Specific Antigens, that signal prostate cancer.
Seeing Tiny Cancer "Markers" Sooner: Purdue Chemist Works on 'Nano' Scale
TOM COSTELLO, reporting:
Mary Wirth knows the value of determination, pushing forward...
DR. MARY WIRTH (Analytical Chemist, Purdue University): We can get close to this really pretty section up here.
COSTELLO: Both in her personal life and her research work as an analytical chemist at Purdue University.
WIRTH: When I really want to know the answer I am willing to put up with almost anything to get the answer. It's like hiking up a mountain. For some people it would look tedious to be walking around all these, these paths up to the mountain but if you really want to get to the top of the mountain you think that's fun.
COSTELLO: Her work might look tedious to some, but for Wirth it’s all part of the excitement of chemistry. In her research, funded by the National Science Foundation, she studies and works with invisible matter, matter on an atomic and molecular scale called nanoscience, something that has fascinated her since high school.
WIRTH: When I took chemistry in high school on the first day of class, our teacher came in with a cigar box with something in it and it was tape shut and we can do everything that we can externally to try to test it but we can never look at it. And so all of us wanted her to take the tape off of the box so that we could see what was in it and she said, that's chemistry, you never get to take the tape off to see what's inside.
COSTELLO: Today, Wirth is able to "shake the cigar box” by using the waves of electrons in her Scanning Electron Microscope or SEM. What Wirth and her team are looking for through these special microscopes are tiny proteins called biomarkers.
WIRTH: Biomarker is, is anything in your, in your blood stream or in tissue that is indicative of a disease. And so they can be DNA. They can be RNA. They can be proteins.
COSTELLO: Wirth is focused on finding specific biomarkers that indicate prostate cancer called PSA, short for Prostate Specific Antigen. PSA is a mixture of proteins found in the bloodstream of all men.
WIRTH: Cancer is PSA, prostate specific antigen and it’s, a small amount is natural in the bloodstream of men and if they have cancer they have an elevated level of PSA.
COSTELLO: But PSA appears in such low levels in the bloodstream that it's often falsely detected by PSA tests, or not detected at all until the cancer is advanced.
WIRTH: We are interested in making the PSA test better as a starting point in early cancer detection.
COSTELLO: Proteins, like the ones in PSA, are also naturally “sticky,” which makes them difficult to test. Wirth is trying to improve the accuracy of PSA tests by using new materials called "nanomaterials."
WIRTH: So what my group does is we make materials that are less sticky, and the idea then is that people will be able to handle these trace level proteins and determine which ones are the biomarkers.
COSTELLO: In many of today's PSA tests, blood samples are placed on a surface covered with polyacrylamide gel. Using an electrical current, individual PSA proteins are separated through the gel to make them easier to see.
WIRTH: The trouble with polyacrylamide gels is that they're very slow for the separations. You have to use a low voltage and wait a long time so the separations take as long as two days.
COSTELLO: Using polyacrylamide gels not only slows analysis, but the gels themselves are weak and don’t hold up well in testing. Under a microscope, polyacrylamide gels look a little like cobwebs.
WIRTH: If you apply a high voltage to that, the proteins start wrecking the cobweb. And so what we do is we make our matrix out of silica, which is like sand compacted together. It's like a rock. The proteins are not going to wreck this rock.
COSTELLO: Silica is probably most familiar to us as the moisture-absorbing gel in those little desiccant packets in the pockets of new clothing. Silica is used because it's both strong and porous, but it’s also “sticky”, so Wirth coats the silica with polyacrylamide, which is less “sticky.”
WIRTH: They don’t have x-ray vision. They can’t see beyond the first layer. And so all we have to do is put one layer of polyacrylamide on the surface and it looks to the proteins like all of the material is made out of polyacrylamide. They don’t know about the rock behind it. So our expertise is putting that very, very thin, molecular thin layer of, of anything on a surface to, to give it the property that we need.
COSTELLO: It's a little like priming a wall before painting it. The primer allows the final color to show up clearer and more defined. Silica gel yields clearer results because - unlike polyacrylamide - it holds up well when exposed to a high-voltage electric field.
WIRTH: The higher the field, the sharper those little zones. And so that's again another advantage of being able to use a very high electric field as you can get really sharp well resolved protein zones.
COSTELLO: These zones are so small that they are nearly invisible to the naked eye.
WIRTH: When we focus these zones really tightly, they're microscopic in size. They're narrower than the width of the human hair.
COSTELLO: And using silica gel also increases the speed at which PSA tests can be done.
WIRTH: The separation is hundred times faster.
COSTELLO: A faster, more accurate method for separating and detecting biomarkers could even revolutionize criminal forensic science, especially the processing of DNA evidence, not only from a crime scenes, but at the crime scene.
WITH: We can make them on little tiny chips and are working on handheld forensic devices that will allow you to do DNA sequencing on the spot. Do it instantly while the criminal is still running away. And, and be able to get the answer much faster.
COSTELLO: From biomarkers for early cancer detection to analyzing DNA for forensic research, Wirth is determined to makes gels more accurate using new microscopic materials.
WIRTH: I would say research is a lot like detective work. There's always a mystery that you're working on. You always have a hypothesis. And then you solve it and it's always a surprise.
CHICAGO — Silver has long been known for its ability to kill some of the nasty microbes that can make people sick. In hospitals, it’s used to help burn victims, to combat germs on catheters and even to wipe out dangerous “superbugs” that have grown resistant to traditional antibiotics.
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