Mindy Leelawong, PhD, Biomedical Engineering at Vanderbilt University talks about a new way to test blood in the field using dyes to detect malaria and possibly other diseases.
Interview conducted by Ivanhoe Broadcast News in November 2018.
Tell me about your research. Where did the idea come about?
MINDY LEELAWONG: The goal of this research was to develop a test that could be used in the field in situations where you see malaria. This test bypasses some critical steps that are very laborious and require a lot of equipment. For example, if you want to do malaria testing in the field using this sensitive test, you’ll need equipment, like, heating blocks and centrifuges, items that require electricity. What I wanted to do was bypass those steps and eliminate that process.
What did you do? What was your method?
MINDY LEELAWONG: The method that we’re trying to use is a sensitive test to detect DNA from malaria parasites. In order to do that, you need very specific conditions. To get these conditions just right, you must go through this long DNA extraction process to eliminate all potential inhibitors. We didn’t want to develop another way to physically remove the inhibitors, but simply find a way to overcome them. One of the main problems with using blood, which is what you need to test because malaria parasites infect red blood cells, is that the blood causes some optical interference. So instead, what I wanted to do was use these dyes that aren’t normally used, but these dyes bypass that optical interference. That allows us to perform the test in the presence of blood. In turn, you’re able to eliminate all the upstream processing steps and make the process easier and deployable in the field.
You mentioned that the blood interferes with optical reading, what is that?
MINDY LEELAWONG: If you look at a tube of blood – especially if you heat it up – you can see it just forms this big clot. It’s not really allowing the light that serves as an indicator of the malaria parasite DNA because you have this big clot of blood. Additionally, components in blood emit their own fluorescence. It provides this optical interference in that way. Traditionally, we can’t read the tube if it has blood in it, unless you use a DNA-detection dye that is a different wavelength of light. This wavelength is a longer wavelength than that coming from the blood.
You’re out in the field in a rural area where it might take a longer process. Explain how you can do in short steps.
MINDY LEELAWONG: If you’re in the field and you want to perform this sensitive test, the problem is you need all this equipment to perform the test. Consequently, usually what happens is you put that blood onto a piece of paper, dry it and then send it to a laboratory where they can perform these extraction steps that get rid of all this interference. It must happen in a central laboratory. By having this instrument and these dyes, we can bypass that entire process and instead be able to perform the test right there on the ground.
The actual instrument itself is like a PCR?
MINDY LEELAWONG: We have an instrument – it’s called Adaptive PCR. The PCR stands for polymerase chain reaction. It’s a reaction that essentially makes copies of DNA over and over and over again. What it does is bring DNA that’s at an undetectable level to something that’s detectable by just increasing the amount of DNA present. We can monitor that increasing DNA using these special dyes. If you have blood present in the tube, you just can’t see those dyes because you have that optical interference. This is what this technology does. It provides a different type of dye that can be used in conjunction with blood. Now you can see those dyes and it’s essentially monitoring the amount of DNA that’s in the sample.
The lab is basically in the field now?
MINDY LEELAWONG: Exactly. Adaptive PCR was made for a field environment. It’s something that is about the size of a shoe box. Ideally, we would like this to be a handheld device. That’s something that we’re currently working on. The idea is that you can bring this out into field conditions where malaria is present, which is often a hot tropical environment with high humidity. Those are all issues with performing a sensitive assay. Having this instrument allows us to perform that right in the field without all the necessary equipment that’s required usually for this process.
The PCR material was with your other colleagues, but you had the actual dye?
MINDY LEELAWONG: Right. This Adaptive PCR instrument was designed before I started working here at Vanderbilt. Once I started working at Vanderbilt, our goal was to take the technology one step further and basically to design a new assay. That was the most difficult assay that I could come up with. Blood is one of the hardest materials to work with because you have so many inhibitors that are present within blood. That was my goal, to use blood and to apply this in a malaria setting.
What implecations do you believe this will have in the medical world?
MINDY LEELAWONG: The goal was to make a sensitive assay more accessible to everyone in the world. We have this tool that we can use in most clinical laboratories. It works well, and it can detect low levels of parasites. But the problem is, if you really want to eliminate malaria, you want to be able to detect very low levels of parasites. That’s just not possible unless you have a central laboratory. What I would really like to see happen is to have these tools available to everyone, no matter where you’re located, no matter how remote the location of your patients.
With this, you’re able to test the drug resistance right away?
MINDY LEELAWONG: Yes, that’s right. Initially I developed this to detect a specific mutation that’s associated with drug resistance. The reason that I started with that is because it’s very difficult to detect a single letter change in DNA. It is a more difficult assay. The idea is that if you can detect this change in DNA, then this provides an indication of direct resistance. Ideally, this will provide a monitoring tool because, right now, we’re seeing some cases of resistance to the first line therapy for malaria. It’s important to monitor and contain that so it doesn’t spread to neighboring locations. This will ensure that we can keep the first line therapy of drug as a viable option for anyone who is infected with malaria.
Right now, it’s being used for malaria, but can it be used for other viruses?
MINDY LEELAWONG: This was something that I developed for malaria, because that’s one of my personal research interests. But yes, absolutely. This could also be used for other pathogens that might be found within blood. Some examples might be HIV or hepatitis viruses.
Anything that I didn’t ask you that you believe people should know about this?
MINDY LEELAWONG: One of the main goals of our work is to provide access to tools that we have available that are very powerful. By making this process easier and more portable, it allows us to bring a technology that’s very powerful into a more remote setting. It’s accessible for everyone.
Now that you’re able to do this in the field, what’s the time difference from how long would you have to wait if it was in the lab or it had to be sent to the lab?
MINDY LEELAWONG: If this is something that you would do in a laboratory, the process would take usually about a day. It takes perhaps four hours or so to process the DNA so that it’s usable for this PCR instrument. Then from there, that would take another hour – and that’s if you have a few samples. Usually what happens is that you do this in a big batch. You have a lot more samples. This is a day-long process. When you’re in a remote setting, it’s not possible to necessarily wait for a day or to be able to contact your patients afterwards. It is important that you speed up this process.
If you’re able to test the blood sample in the field, you could try it out on the patient’s blood sample first before even administering it to the patient, seeing if the drug resistance of that drug will work with them?
MINDY LEELAWONG: Exactly. In the case of drug resistance, it’s important to know if someone has some resistance to that drug, because otherwise that drug is not going to be effective. If you can do the testing right at the very beginning when someone is first diagnosed, then you’re going to give them a more effective treatment.
END OF INTERVIEW
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