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Dr. Krystal Pollitt on How Collaboration Across Yale Feeds Innovation

Date:
10/25/2023

Dr. Krystal Pollitt on How Collaboration Across Yale Feeds Innovation

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fresh air

Dr. Pollitt is an Associate Professor of Epidemiology at the Yale School of Public Health (YSPH). Her lab studies environmental exposure via the collection and analysis of complex environmental samples using mass spectrometry techniques. In addition to her research, Dr. Pollitt is an entrepreneur and, with her interdisciplinary team, has developed the FreshAir wristband, a wearable device that detects air pollution. Pollitt recently spoke with Yale Ventures about her research and entrepreneurial journey.

“Yale is a really fantastic hub of people to collaborate with and it's allowed me to work with people from engineering to public health, medicine, and architecture, to develop this concept.”- Dr. Krystal Pollitt

 

Exposure to air pollution is unavoidable and ranks in the top ten global health risks. How does it affect the human body and contribute to disease? 
There is a degradation in air quality and, especially after the wildfires that happened last month, lots of air pollutants that we're all aware of come from a number of different combustion sources, be it from wildfires to gas stoves to the tailpipes of our cars.

Many pollutants are known endocrine disruptors, or have other pathways in which they will act to induce adverse health effects, be it from respiratory conditions for a number of air pollutants, but also going well beyond to cardiovascular, neurological metabolic, developmental, reproductive, you name it, there's going to be some sort of adverse effects that is induced.

There's also a number of other sources of pollutants in the air and a number of other environmental matrices. These pollutants can result from the cosmetics we use, our home furnishings, clothing, building materials, and more. It's these contaminants that I am interested in assessing the exposure to, because many of them have emerging contaminants that we don't know the defined health outcome of. We're looking to be able to have tools that we can use to better measure exposure at the individual level. We can then use those in epidemiological studies at the population scale to better define those adverse health outcomes.

Can you talk about the urgency of our pollution crisis? 
When we just think about criteria air pollutants (those that are regulated), we know that so much of the world is exposed to exceedingly high levels. Even in the past month, so much of the U.S. was exposed to astronomic levels of poor air quality that we're not used to seeing. If, going forward, this is much more of a regular occurrence, it really is a major public health concern to be dealing with levels that are 10 times higher than regulatory limits, much higher than what we're used to seeing in New Haven and beyond. According to the American Lung Association, “More than 1 in 3 Americans live in places with unhealthy levels of air pollution” (“Key Findings: State of the Air”).

We can also start to think about many different pollution sources coming together and how they layer upon each other. We're not only dealing with the impact of wildfire exposures, but then we also have our indoor pollution from all the other sources that were normally exposed to. We're seeing an emergence of new pollutant types that are very concerning, including PFAS, and we’re starting to explore how that interacts with other pollutants. So, in addition to looking at pollutants of concern, where we use known authenticated standards to validate what we're seeing, we also do what's called a non-targeted analysis, where we're just screening across previously unknown compounds and trying to then assign a chemical signature to that compound. To be able to see the emergence of compounds that we weren't expecting in some places is definitely interesting.

The Fresh Air wristband is a lightweight, wearable air pollutant sampler. How does it work? 
The wristband is what we call a passive sampler. We don't use a pump, or any electronics. We have developed a polymer membrane that passively absorbs compounds. This membrane is composed of a silicone-like material.With this material, there is no selection in terms of the type of compounds that are taken up.

We embed this polymer into a wearable device, wristbands, because lots of people wear something on their wrist, and they're agreeable to that. We can fabricate the wristband into lots of different colors and styles that are desirable for a range of different people to wear. Additionally, we have it in a clip-form that you can put onto the lapel of your shirts, and we also have it embedded in ankle bands that we can put on to very young kids, including newborns and infants. Because of its size and design, it's not a choking hazard, and young kids can freely move about with the wristband. At the same time, we’re still able to collect the pollutants to which they're exposed. If they're on the ground more, we're picking up on all of those compounds that are closer to the ground, be it volatilized in the air or associated with dust.

How are pollutants identified and analyzed?
Identification: 
We have a polymer that's embedded into a wearable design. Someone will wear the device for about a week, return it back to the lab, and then we do the chemical analysis. We use a gas chromatography high resolution mass spectrometer, which allows us to do very detailed chemical analysis.

Once the wristbands are received, we remove the components of the wristband and put them on to an auto-sampler. This allows us to do a high throughput analysis, and we can do hundreds of individuals at a go. Then, they’re put into an oven mounted on top of our instruments, which bakes off and volatilizes all of the compounds absorbed by the silicone. Then, we direct that airflow onto our gas chromatography units, which separate those compounds out. Next, we direct it into the mass spectrometer, which allows us to get a chemical fingerprint of the compounds that were within the wristbands. The technique lets us get at 500-600 compounds for each one of these wearable devices.

Analysis: 
What I love so much about this work is that it allows us to be creative with the engineering design for the hardware, and then we can apply our analytical chemistry training to do the analysis. We have a whole computational backend to then deal with the incredible amount of data that we get for each sample. We have computational workflows to be able to annotate each one of the peaks that come out of our instruments with a chemical identity. With that, we can then determine the concentration for each one of the compounds one was exposed to. It’s a very comprehensive exposure assessment that we can do at the individual level, be it if you are six weeks old, six years or sixty years old - we have a wearable device that will meet the needs for each age group.

An Automated Process:
We recognize that if we wanted to have any impact with this work, we couldn't have a type of analysis that would take hours to process for one person. The real utility in this is being able to aggregate and provide information for a very large number of individuals. We regularly process 1000s of different samples. The goal is to not only provide individuals with their own exposure, but also identify trends across different age groups, geographies, and types of environments. We use some vendor-based software, depending on the point within the analysis, but much of the software we have developed in-house to to optimize our workflows.

How many pollutants are you focused on in your lab? 
Because we are exposed to such a complex, diverse mixture of pollutants that is incredibly long in number, we're not focused exclusively on a single class of pollutants.

Because the way that we collect airborne contaminants is non-selective, we don't target compound X or Y, we are capturing the full range of compounds. The analysis technique that we're using is similarly able to screen for compounds in a non-targeted fashion.

We're looking to be holistic in terms of how we evaluate exposures, and the wearable technologies that we've developed are able to capture hundreds of different pollutants in a non-selective manner.

The wristband presents an incredible method of assessing exposure among vulnerable populations, especially young children and pregnant women. Once a user has the data, how can they take action?
This aspect of the project has been a major activity within the lab right now. It’s a phase that we're currently trying to refine further because we can measure 600 compounds, and my mind is always jumping to ‘what's the identity of these compounds, and do we know the clinical or toxicological significance of them?’

We are using these wristbands in large scale epidemiological studies as a tool for exposure assessments. This is being done alongside assessments of different biomarkers that may be preclinical responses or those that are looking at clinical endpoints. We are looking to develop exposure report packs to highlight key compounds of concern and relate that information to different epidemiological or health-based studies. We can then better understand if there should be interventions brought forward, or some strategies to reduce exposure if we know what the source is. Depending on the population that we're working with, we recognize that how we report back and what we report back should be different.

​​We've been really fortunate to work with a number of different collaborators in lots of different countries. We will typically ship out wristbands to where the study is based. The wristbands will be designed and packaged to accommodate the needs of that population. In some cases, we're working with kids, in other places, we’re working with older adults. There may be cultural sensitivities that we're looking to accommodate based on clothing choices or color preferences. The field team will deploy the wristbands with the study team, or we will simply mail them out directly to participants, depending on geography. Participants will wear the wristbands for about a week, and then return them back to the lab, where we do the chemical analysis that I described. Once we have all the exposure data, we then pair that with the outcome data that we're also collecting for that study.

How did you come up with the idea for the Fresh Air wristband? 
I've worked within air pollution for all of my graduate training. Throughout those years, I was working with personal monitoring equipment, looking at individuals' exposure and linking that to various health outcomes. There was always general frustration with the fact that what was termed to be ‘wearable’ really wasn't. You kept looking at these brute force solutions that had been put together to evaluate exposures - it would usually amount to getting very expensive technology, 1000s of dollars a piece. You would then aggregate that technology into a large backpack and ask someone to wear it. This methodology is not providing a true estimate of what their exposure was, because if you tried to put that on to a child, they would leave it by their chair at school or on the corner of the field during a sports match, which is really not capturing what they're being exposed to. We had to ask ourselves, ‘What's our exposure misclassification? What are our biases with these technologies?’ It was just this continual thinking of ‘how can we make the technology smaller, simpler later, or more cost-effective?’ It took everything of me, as an engineer, to strip away everything else we wanted to measure and simplify the technology. We just kept stripping things down, taking away what we did not need, and then introducing that on the back end, so we could still then think about all of those complexities within exposure characterization, but not have that on the person. This way, we get a much more realistic assessment of exposure.

How has Yale and  New Haven been a supportive innovation partner for your entrepreneurship journey?
Yale’s been a really fantastic hub of people to collaborate with and it's allowed me to work with people from engineering to public health, medicine,and architecture, to develop this concept of exposure assessments. With our colleagues in architecture, we even developed designs of our technology that integrate stationary locations into buildings. Overall, it's been a fantastic spot for coming up with innovative ideas and moving this whole concept to reality.

Yale has also been great in providing us with the resources to be able to do this work, and the capacity to do so with really incredible students that have led this work forward. For example, a PhD student within my lab, Elizabeth Lin, has been an amazing leader of this technology. I've been working with her for the past six plus years on developing the wristbands. She presented at the 2023 Yale Innovation Summit at the end of May and is looking to spin this technology out to enable access to the general public.

We now are looking at how we can scale up because we recognize that deploying these wristbands in epidemiological studies provides incredible insights from an academic perspective on emerging contaminants as well as health outcomes of concern associated with exposures. Getting to the scale where we can enable this technology to be usable within the general public is also a great unmet need, especially for cases in which individuals have concern about an exposure in the case of exposure disparities, or those that are living with a pre-existing health condition who want to be able to manage their symptoms.

How can we support women and underrepresented entrepreneurs?
There are definite hurdles in developing new technology and getting the buy-in for the technology - that, in itself, is a challenge to overcome. Still, working at Yale has definitely equipped us with the necessary resources to make sure that we can validate and scale up our technology; There are many networks available and incredible students, a number of whom have been women that I've been fortunate enough to work with. Having female students within the pipeline for mentorship will really allow for them to to progress further and and continue this innovation.

What is your best advice for those interested in entrepreneurship?
I think the persistence in developing the technology has been the most important. We've come across a lot of resistance to develop the new technology:

This wearable form for evaluating exposure in a very small scale that doesn't require electronics is a shift from how exposure assessment has been previously done. There were traditional approaches of using quite bulky equipment that had a lot of historic use within the fields, or the use of biological samples.

It took a lot of validation of our current technology to demonstrate the power and the range of exposures that we are able to detect. Showing the robustness of the technology has also been a key challenge. We have done validation for the past 5-6 years, and we are now seeing buy-in from a critical mass. We've been able to continually validate, answer questions, and demonstrate our enthusiasm and need for this technology. We've overcome these barriers and can actually do the science that we've been wanting to do for so long.

I think that's probably the best advice that I can tell others: persist - put your head down, and keep on going forward for the technologies that you think strongly of.

Sources:
“Key Findings: State of the Air.” State of the Air, www.lung.org/research/sota/key-findings. Accessed 4 Aug. 2023.