There is no safe level of lead in blood; even low levels of lead in blood are associated with developmental delays, difficulty learning, behavioral issues, and other harmful health effects in children. That means next-generation point-of-care blood lead tests will need to be incredibly sensitive. Fluorezyme, one of five Phase 1 winners that advanced to Phase 2 of the Lead Detect Prize, is using DNA and light to identify and quantify trace levels of lead in a small amount of blood.
Through August 2024, the Phase 2 teams participated in a virtual accelerator designed to help them advance their point-of-care blood lead detection solutions. The goal of the multiphase Lead Detect Prize is to enhance the detection of low levels of lead exposure through blood tests administered at the point of care.
We spoke with Wei Yu, CEO of Yureka LLC, from the Fluorezyme team about the dangers of lead in children, how the Fluorezyme team is using DNAzymes and fluorophores in its point-of-care platform, and the importance of subject matter experts in the accelerator.
How did you find out about the Lead Detect Prize? What motivated you to enter?
I’ve been following Challenge.Gov for a couple of years now, and I think it’s a really great avenue to solicit ideas from the general public. It’s a little bit different from the traditional academic or commercial setting because it has that ability to reach a wider audience and the general public can contribute. I have a background in bioengineering, specifically with developing and making biosensors; so when I saw this challenge announcement, I thought it was a chance to contribute to solving a problem that has quite a big impact on our population. The motivation was to try and address a critical issue that is affecting an important segment of our population. And of course, I’m not doing this alone, I have a great team with me.
What do you find most inspiring or challenging about lead detection?
There are already a lot of techniques for detecting lead. Even though those solutions exist, lead poisoning is still a problem. Even very low concentrations of lead will have a significant effect, especially in children. The aspiration is to come up with a better and more effective solution to identify or detect the problem early in their lives — and to help medical professionals offer a solution to prevent the negative impact. The challenge, of course, is that you’re trying to detect such low concentrations of this metal and you have to do it very reliably and accurately. A big part of the hurdle is that we’re not looking for lead in a simple matrix like water — which is relatively clean — but we’re working with blood. And with blood, there are so many different components, including proteins and cells. All those components have an influence on how accurately you can perform a measurement.
Another challenge is to make a test that is easy to use so that an untrained person can run it. Not only do you need to make it very accurate and precise, you also have to make it so that someone with no knowledge of chemistry or how to run an assay, can just follow a simple set of instructions and get a reliable result.
Tell us about the technology or solution you are working on. How will it improve lead detection?
Our approach is based on a concept called DNAzyme. A DNAzyme is a very short strand of DNA that has special binding properties to an analyte. There are very specific sequences of DNA that bind to lead, and we call them leadzymes. When the leadzyme binds to a lead ion, it acts like an enzyme and chops up a complementary strand of DNA. If we label the DNA strands with a fluorescent dye, then when the lead comes in and binds, the DNA will get chopped up and all the dye molecules are released. We use a handheld fluorometer or a camera to capture the light from the released dyes.
The advantage of this approach is that the lead is not consumed in this enzymatic reaction. It only takes a very small amount of lead to cause the release of many dyes. We can achieve very high sensitivity, even at very low concentrations of the lead in the blood. But the other aspect of it is making use of portable equipment, like a portable reader, that a user can carry out in the field. We want to be able to use existing cameras, such as cellphone cameras, to make it more accessible so the user doesn’t have to purchase an expensive piece of equipment for the measurement.
We are making good progress toward that goal. It gives us the ability to get real-time data and be able to immediately measure the lead concentration in the blood of the patient, instead of having to take the blood and then ship it to a centralized lab and wait a week for it to be analyzed. We hope to skip that process so that the medical professional or doctor can then act on the information and deal with the problem more quickly and effectively.
What have you learned about lead detection in children since starting the challenge?
Before I entered the challenge, I had believed that lead poisoning was a problem of the past. I thought that there were techniques to measure it accurately and treatments to deal with its effects. But what I found, as I delved more into the research and existing literature, is that it’s still a significant problem, especially in areas where you have older housing with lead paint or old lead pipes. That was an eye-opener for me. When you are living in a newer house or a newer apartment, you don’t think about this. But there are some segments of our community where those problems persist. It was quite revealing.
I feel that we need more urgency to tackle this because children are quite vulnerable to it. We don’t want them to grow up suffering from a problem that shouldn’t exist.
From talking with the experts, measuring lead in kids is harder than in adults because children may not be willing to sit still and let you take their blood. You’d have to get the sample very quickly and you have to make use of very little of it and get a result.
We also need to make the test widely available and accessible. In the major urban centers, you can get a sensitive lead test done very easily. But for our rural communities, there’s no opportunity to travel to a centralized lab and get the test done. Accessibility is an important factor that we have to address.
What has been the most valuable part of the accelerator so far?
It was great participating in the accelerator sessions. We got the opportunity to speak with experts in different areas. We received a lot of feedback about the ideas that we proposed and also a lot of insight from them about the current problems of getting a lead test done.
It was very helpful to hear their comments and their feedback; it helps us to improve the design of our test. And it was also great to hear from regulatory experts because regulation is always challenging to navigate, especially if you’re trying to get a medical device to market. Having insider knowledge and tips from experts at the FDA and CDC on how we can efficiently manage the 510(k) and CLIA-Waiver processes efficiently is invaluable for us to get the test into the marketplace.
What role do laboratory standards play in innovations like this? How do they enable innovation?
You should always have a set of standards so that you can define reliability, accuracy, and precision. Laboratory standards give us benchmarks to guide the development of the assay, and metrics to validate the performance of our new test. They tell you what methods already exist, what they’re able to achieve, and what would be an improvement over the current state of the art.
What are your biggest development priorities moving forward?
We have obtained very good preliminary results, but there is still a lot more work to be done before we have a market-ready device. There are certain development goals in the pipeline that we’re trying to achieve.
First, we can improve on the sensitivity and the accuracy and try to push the envelope to be able to detect as low as we can and beyond what is currently available. We have to remove interference in the blood by optimizing sample cleanup, and we really want to make this process as simple as possible. You don’t want the user to have to go through multiple steps to get a result. If we integrate some of those steps and make it simpler so that all they have to do is put a drop of blood onto the device and be able to read the result, that would be ideal.
Behind the scenes, we would have to improve the detection algorithm. Because we are taking a light measurement and converting that to a lead concentration reading, we have to make sure that the data processing works reliably and gives a result that is accurate.
In parallel to having those things in place, we need to develop partnerships. As soon as we have an assay that can be used, we want to get it to our partners so that they can start testing and give us – feedback about the user interface, precision, and accuracy. This will help us to come up with good, reliable, and easy-to-use tests that we can then release to the market and protect our children from lead poisoning.
Looking ahead: Demo Day at the Milken Institute of Public Health in Washington, D.C.
On October 24, the Lead Detect Prize will host a Demo Day at the Milken Institute School of Public Health at George Washington University. During the event, the five Phase 2 teams will showcase their lead detection solutions, and the winners of the $850,000 Phase 2 prize pool will be announced.
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