SERS-based project targets disease biomarkers at point of care

In a recent episode of the “All Things Photonics” podcast, Photonics Media spoke with representatives of the Precise Advanced Technologies and Health Systems for Underserved Populations initiative, or PATHS-UP. The National Science Foundation-funded collaboration between research and industry targets the advancement of positive R&D outcomes beyond the lab and into the wider community.

Hosts Jake Saltzman and Joel Williams interviewed three key representatives in the effort: Samuel Mabbott and Cyril Soliman of Texas A&M University, and Michael Matthews of Wasatch Photonics, who together used surface-enhanced Raman spectroscopy (SERS) to detect core biomarkers at the point of care. They discussed the process of perfecting the analysis and conjoining instrumentation, as well as the long-term prospects for bringing it into the medical marketplace.

Below is an abridged and amended version of our interview.

JOEL: The ability to assess and then treat cardiovascular disease rapidly and at the point of care is one example of an endeavor that would go a long way in reducing rates of morbidity and mortality on a global scale. The Precise Advanced Technologies and Health Systems for Underserved Populations, or PATHS-UP, initiative aims to integrate engineering, research, and education with technological innovation to transform national prosperity, health, and security.

Two PATHS-UP students, Angela and Nhu, are using a Wasatch Raman spectrometer to analyze their samples. Courtesy of Texas A&M University.

Samuel Mabbott is assistant professor in Texas A&M University’s department of biomedical engineering. His charge in the PATHS-UP work is the development and implementation of a spectroscopic system that is portable and multimodal for point-of-care optical biosensing applications.

Cyril Soliman, a Ph.D. candidate at the time of this recording, led the project. Fluorescence and colorimetry were among the technologies first considered. They achieved a SERS platform to reach the sensitivity required for biomarker detection (cardiovascular) at the point of care.

Michael Matthews, VP for spectroscopy at Wasatch Photonics, was the critical link to industry and development of the multimodal spectroscopic systems for proof of concept.

SAMUEL: At PATHS-UP, we’re developing lots of different types of devices aimed at diagnosing and monitoring chronic diseases such as cardiovascular diseases and diabetes. In their simplest form, the devices consist of assays for targeting biomarkers and the reader systems, which often incorporate techniques such as spectroscopy. The idea is that when we develop an assay, we need to be able to read the signal output. And that’s where collaboration becomes important, such as working with industry groups like Wasatch Photonics. The main aim for us is to make those more affordable and more accessible, so we diverge from what might be already available to develop new technologies.

Samuel Mabbott, Michael Matthews, Cyril Soliman

JAKE: So the initial goal of this particular work was always a point-of-care platform. Cyril, for you as the researcher, at what point does research and investigation into a diagnostics platform in the lab begin to necessitate consideration of extending the work beyond just that setting and into point of care?

CYRIL: We already knew that we wanted to get to something that’s handheld for an underserved community. I tried to pick low-cost components and do things to miniaturize and make the system as cheap as I could, but I couldn’t really jump over that next hurdle of bringing it to a truly handheld point-of-care device. So that’s where I had the privilege of meeting Michael from Wasatch Photonics. With them being on our industry advisory board, I got to talk to him at one of our annual meetings. We set up a connection to talk about what technologies they have that could help bridge that gap for us and bring that device from the laboratory into the hands of the underserved community.

MICHAEL: We see a tremendous movement in the health care industry looking at Raman and other spectroscopy-based techniques to push diagnostics as close to the end user as possible. At Wasatch, our technology base is centered on making Raman instrumentation smaller, more powerful, more accessible, and easier to use. So there’s an overlap in what we’re trying to do from the instrument point of view and the need that Cyril just mentioned.

JAKE: I should mention that we’re talking about extremely high sensitivity Raman measurements. And we’re also talking about optimal biomarkers. So, Sam, I will ask you, how do we determine the optimal biomarkers to be targeted for any application, or for this one in particular? And, and as a follow-up to that, what technologies are needed to detect those targets?

SAMUEL: It really depends on how sensitive we want to go, and it depends on what the end user really wants out of that system. One of the technologies that we work on is a technique called surface-enhanced Raman scattering, where we can get unique, ultrasensitive signals from whatever we’re trying to detect. But we can also go for colorimetry, which is more akin to what you see with a COVID-type test, where you see a color if it’s a positive result, and nothing if it’s a negative result. We have a range of different ways to do it. It just depends on what the end application is, and which one is most feasible for the diagnostic assay that we want to develop.

JAKE: I want to ask about surface-enhanced Raman spectroscopy, and the advantages of that technique. Certainly there are some, but for this application, what drew you to SERS, or maybe what drew SERS to you?

SAMUEL: The idea (of SERS) is that if you take a molecule of interest and you bring it into close proximity to a nanoparticle, you create a much higher and more intense Raman signal, which then means we can adopt it within these diagnostic tests to give us the ability to detect biomarkers at much lower concentrations.

An illustration of an assay for cardiovascular disease developed by the PATHS-UP collaboration. Courtesy of Wasatch Photonics.

The design of a Raman multimodal instrument developed by a collaboration between Wasatch Photonics and Texas A&M University. Courtesy of Wasatch Photonics.

JAKE: For productization, we’re talking about an instrument as well as an assay, right? We have two different things, and we don’t want them to be overly reliant on one another. Can you just outline for us, Michael, what moving from point A to point B in commercialization looks like?

MICHAEL: I think, in the realm of Raman, it’s still being figured out. There aren’t yet any FDA-approved Raman-based assays out there, although there are a tremendous number of them across a broad breadth of potential targets that are being developed and in various states of trial development. So I think there is a little bit of uncertainty as to what it’ll take to get past that final hurdle and actually get some of these devices and some of these assays into the back of an ambulance or into a doctor’s office. But there is such a defined need that we know it’s going to happen.

What we look at, first off, is the assay and instrument, and these can be developed completely separately. Any Raman instrument can read markers, and to a certain extent, our instrument can read any Raman-based assay designed for the appropriate wavelength. So these are not dependent on each other in terms of the development. However, the earlier in the development cycle that you start thinking about this as a whole system, the better. You need the assay, the instrument, a workflow, and you have to have all of that working together to be successful.

JAKE: I suppose I have the same question for you, Sam, but on the research side: When you’re thinking about prioritization or moving toward making a commercial push, can you just walk us through the links in the chain there that you’re trying to address?

SAMUEL: From the assay development side, if we know what the desired sensitivity is, we have a range of techniques that we can pick from in order to successfully achieve biomarker quantification. We can also switch out different elements from the recognition side and the assay side to boost signal amplification, thus realizing much greater sensitivities.

The main issue that arises, especially with some techniques, is the reproducibility of that signal; that is one of the hurdles we need to overcome. With the Raman (readers from Wasatch), they perform exactly the same way, every single time; it’s a piece of excellent hardware that will measure the signal from our assays. We have to emulate that reproducibility in our assays for it to be a reliable testing platform — and there’s a lot of stages we have to go through in order to reach that goal. Typically, we start with spiked sample testing in the lab, whereby a known quantity of biomarker is added to a solution or buffers. Then we’ll progress into complex sample matrices and eventually to human samples.

JAKE: What occurs to me is that all of this work for the last handful of years is occurring against the backdrop of a global pandemic. Cyril, you’re leading this effort against that backdrop. Is that weighing on you at all in the back of your mind?

CYRIL: It’s something that we’re definitely thinking about, and for us, it’s a big motivator. We saw the impact that a lot of these point-of-care devices had immediately during the COVID-19 epidemic. Since we needed tests rapidly for COVID-19, research was expedited, and those tests entered the market quickly. But you also saw there were a lot of questions that arose regarding test reliability and repeatability. At the end of the day, we want reproducibility and repeatability in these assays. And that’s really the guiding principle that is going to remain consistent as you talk about anything in the biomedical diagnostics field.

JAKE: The pandemic and portable handheld diagnostics are always going to be linked. But I don’t know how many have been tasked with designing such an instrument. Any thoughts?

MICHAEL: It would be so beneficial if we could pick up a patient who’s had a heart attack and — right there in the ambulance — get one or two extra readings to start their diagnosis and the proper course of treatment that much earlier. The research starts on that, and then you have to get the science, the engineering, and the business case all to work together. Scientists prove what might be possible and the optimization that Sam was talking about. But then you also have a business out there willing to pay for it. Are there codes that you can bill against in the medical world? Are there foundations who will help us to get this technology to underserved populations? At the end of the day, it has to be practical, and possible. And that is very much a continuous effort of optimization to make it work a little bit better, to make it a little bit more effective, to make it a little bit more cost-attractive.

To learn more about PATHS-UP’s mission, visit their website at pathsup.org. For the unabridged podcast interview on the PATHS-UP initiative, visit www.photonics.com.