A Closer Look at Developing a Lab on a Chip for Oral Cancer

August 2007

Dr. John McDevitt, a scientist at the University of Texas at Austin, is one of several NIDCR grantees currently developing a first generation of miniaturized, fully automated saliva-based diagnostic devices.  As part of the NIDCR grant, the McDevitt laboratory published in the August issue of the journal Lab on a Chip the results of proof-of-principle experiments for a rapid chip-based diagnostic test for oral cancer.  McDevitt spoke to the Inside Scoop about the device, its status, and future prospects.  

It started a few years ago when Dr. Spencer Redding, one of our dental collaborators at the University of Texas Health Sciences Center in San Antonio, invited us to come and collect oral cancer samples.  At the time, we had a research effort under way to develop a blood-based test for cancer cells.  As a chemist who spends his time ensconced in a laboratory, I found the visit to the dental clinic absolutely fascinating.

Well, it gave me an appreciation of the difficulty that dentists and oral surgeons face in diagnosing oral cancer.  A dentist, for example, might see a patient with an unusual sore, or lesion, under his tongue.  But how far do you go to find out whether its cancerous or just a bad inflammation?  Should the dentist take a biopsy that can cut into muscle and blood vessels in the tongue and risk leaving the patient in pain and discomfort for several days?  I learned that day that to biopsy or not to biopsy is not an easy decision.  Spencer told me that dentists would benefit greatly from having better tools at hand to allow them to make a more informed decision.  He said that especially applied to detecting recurrence in oral cancer survivors.

And how did you make the transition from the blood-based test to a microfluidic lab on a chip that is the subject of this paper? 

It’s kind of an interesting story.  Our laboratory had a grant from the NIDCR to develop miniaturized, chip-based tests that use saliva as the diagnostic fluid.  So we already felt comfortable working in the mouth.  After the trip to San Antonio, I realized that we could apply that knowledge to design a better diagnostic tool for oral cancer.  From that point, our work on cancer narrowed conceptually from the blood-based general test to a tighter focus on the mouth. 

But this test doesn't use saliva, does it?  

No, we’re currently using a brush biopsy to collect cells from inside the mouth.  In other words, we brush away cells from the lesion, resuspend them in a special fluid, and introduce a drop of the mixture into our lab on a chip for analysis.

By conveying them into a small chamber on the chip and filtering out the fluid.  The process works like this:  After we load the drop of fluid into the device, the mixture passes along a tiny microfluidic channel and pools into the chamber.  The chamber has a porous membrane floor that, like emptying boiled ravioli into a colander, drains out the fluid and leaves the larger cells behind and isolated on the floor of the chamber.  At this point, a cocktail of antibodies is automatically pumped into the chamber through the holes in the floor.  The antibodies are labeled with fluorescent dyes and, in our proof of principle experiments, were programmed to attach to a protein displayed on the surface of the cells called epidermal growth factor receptor, or EGFR.  This protein receptor tends to be overexpressed on many common types of oral cancer.

Exactly.  We’ve created a nice miniaturized platform with a digital camera interface.  It allows us to see the fluorescence on a computer screen and quantify the bound antibody on the cell surface.  The chip essentially automates a process that is now done manually by a pathologist.  Think of it as “pathology on a chip.”  We’re using fluorescent stains instead of the standard dyes that a pathologist employs.

We’ve already begun to do so.  Once the cells are on the floor of the chamber, we can pump in not only antibodies, but stain the nucleus of the cell and evaluate its DNA content.  The approach is very flexible and scalable.     

You mention in the paper that the chip produced results in about nine minutes.  Will the chip become slower as you program in multiple biomarkers? 

I don’t think so.  You mentioned that we already have developed a chip to test HIV status and immune function.  That chip measures four different biomarkers, and it takes about eight minutes to complete, which includes software manipulation and collecting the sample.  So, I feel confident that we’ll produce an oral cancer screening test that can be completed somewhere between five and ten minutes. 

You’re right, and that was one of our main goals.  Right now, if a dentist suggests that a patient have a biopsy, it often leads to a lengthy process to make a diagnosis.  The patient often will need to schedule an appointment with an oral surgeon for a biopsy and wait from three to seven days for the results from the pathology lab.  We looked at the inefficiencies that are built into the process and envisioned a different scenario.  What if a patient with an unusual oral lesion provided a sample of cells at the start of the visit, had their teeth cleaned or a cavity filled or their teeth, and picked up the results of their oral cancer screen before they left the dentist’s office?  Obviously you don’t make the final diagnosis in the dentist’s office.  But patients could consult with their dentists immediately and discuss the next steps.  That’s empowering.

It’s not labor intensive at all.  As mentioned, we designed the device with the busy pace of dental or medical offices in mind.  The chip is fully automated, and sample preparation is straightforward.  Staff won’t need to culture cells or perform any time-consuming chemistry in between patients.  In fact, the device is about half the size of a toaster, meaning it won’t take up much office space. 

That’s right.  It’s always a challenge to take the needs of biology and adapt emerging technologies to them.  But we had worked hard toward this goal.  Take the HIV chip that I mentioned.  It is technologically sophisticated, but we developed it for field use in resource poor settings like in the African nations.  The end product had to be fast, easy to use, and have great diagnostic sensitivity and specificity.  Otherwise, it would be of little benefit to a nurse or physician in a rural setting.  But we did it.  We started at the nanoscale and built a diagnostic device that, as I mentioned, evaluates four biomarkers in about eight minutes. 

We want to fold in additional biomarkers and make the information content richer.  We know we can do it, and we already have a headstart.  As this hurdle is cleared, we will work closely with our clinical collaborators to conduct studies to evaluate rigorously the chip’s sensitivity and specificity.  That will put us at the point of care with a test that can diagnose or prognose oral cancer.   We’ll need to evaluate the device against the current gold-standard tests, and we’ll see how well we do. The process also will give us a chance to fine tune and optimize the test along the way.  If all goes well, we’ll have a hand off at some point in the next few years to make the test available for real world clinical practice. 

You bet.

To read more about the McDevitt laboratory, please visit:   http://www.cm.utexas.edu/Faculty-and-Research/Faculty-Directory/Individual-Faculty-Pages/john_mcdevitt