Science Diction Podcast | Field Forward

Dr. Amy Manning-Boğ
A wet market in China, a bat colony in Germany, a tiny tick in the Midwestern U.S. Infectious diseases can emerge from anywhere in the world, and when they do, it’s critical that officials are prepared with the necessary equipment and expertise to detect and diagnose them with the goal of maintaining public health.

Jennifer Stone is principal scientist with expertise in the development and validation of new devices for automated sample preparation and analysis, novel extraction protocols designed to accommodate challenging matrices and organism types and specialized library preparation methods to prepare these extracts for next gen sequencing.

She also specializes in development and adaptation of these detection and diagnostic methods for use in field forward environments that have space, time, and resource constraints. Today on the show field forward detection and diagnostics, how they’re developed, the diseases they may detect, and their role in providing life-saving treatments to patients in remote areas of the world. I’m Amy Manning-Bog, and this is Science Diction from MRIGlobal.

Jennifer Stone, MS
So when we’re talking about the field forward need, we’re often talking about things that aren’t really a concern in the U.S. and the U.S. isn’t used to combating. Those can be mosquito and tickborne diseases. Some of the tropical diseases like Dengue, Zika, yellow fever. It could also be the scary hemorrhagic fever viruses like Ebola, Marburg, Crimean-Congo, and also things that could be, but hopefully aren’t, relevant to combat zones and warfare threats like plague, anthrax, and tularemia.

Dr. Amy Manning-Boğ
So what’s the threat that these diseases pose?

Jennifer Stone, MS
These diseases can have devastating impacts on public health leading to outbreaks that overwhelm healthcare systems, cause economic disruption, and in many cases result in long-term health issues or even death. 

And some of these also have been known to cause birth defects, Amy, like Zika virus. Beyond the health consequences, there’s a very real economic impact. Today we live in a true global economy and the access to travel is so widespread that things that used to be local endemic concerns now have the possibility to leap countries and continents and become a true global pandemic.

Dr. Amy Manning-Boğ
When I traveled back from Europe to visit my husband’s family, that’s when I came down with COVID. Wonderful times in the airplane with 200 of my closest friends.

Jennifer Stone, MS
I mean, the whole world is just so linked now. Nothing is local anymore. Everything can go anywhere with anyone.

Dr. Amy Manning-Boğ
What interests you in this area of work, Jen?

Jennifer Stone, MS
Well, the challenge of miniaturization really fascinates me. We’re talking about diagnostic tools that used to be the size of a fridge, and now we’re shrinking them down and putting them in the palm of the hands of people all over the world, and I mean literally the palm of their hand. Some of these are very small handheld devices. This combined with the integration of smartphone-based diagnostics is really revolutionizing how and where we can detect diseases making diagnostics accessible even in the most remote areas.

It brings diagnostics and detection capabilities that used to be limited only to large, advanced labs in high tech countries, and we’re able to put that technology into the hands of people all over the world.

Dr. Amy Manning-Boğ
The democratization.

Jennifer Stone, MS
Yes. Yes. And literally into their hands, Amy, because these things are so small that they’re in fact handheld.

We see a lot of things kind of in that pack of gum size to credit card. There’s a lot of credit card style diagnostics. Some of them are a little larger if they’re more complex, but even so those are kind of the size of a brick maybe. Definitely something you could put in a backpack or carry with you.

Dr. Amy Manning-Boğ
And hence it can get to these remote environments.

Jennifer Stone, MS
Exactly.

Dr. Amy Manning-Boğ
So when you’re taking this into account, portability of course is important to get to the remote environment. What else do you have to consider when you’re developing a device like this?

Jennifer Stone, MS
Yeah, so some of the concerns are about the device itself. Besides being small and portable, it also needs to be rugged because it could be dropped, it could be thrown in a backpack, it could go anywhere. It’s also important that it’s battery operated, since you can’t really go into a remote forest and be able to plug something into an outlet, it’s just not going to be available. They also need to be able to function without things like Wi-Fi or other communication and be something that you can operate in temperature and humidity extremes, as well as dusty environments.

And besides the device, I mean the other thing people don’t really think about is that it’s also about the reagents and the consumables being used. Those have to have those same things that we talked about for the device, but on top of that, cold storage is really nearly impossible in these remote environments. So we have to take things that usually have to be in a freezer and convert them into a fashion that can be used at ambient temperature and from anywhere that’s really hot, possibly someplace frozen. So we’re talking about things like lyophilizing or freeze drying these reagents.

Dr. Amy Manning-Boğ
Oh, wow. And these have to be really rapid reactions too.

Jennifer Stone, MS
Yes. Yes. They have to be fast turnaround time is really important. Field operations mean mobile operations, so you don’t have time to sit around and wait for the results. Also, in a field setting, you usually have a limited number of devices. So traditionally you think, well, I can just scale up my testing by having more devices, but how many devices can you really take into the field with you? So, time to result in that situation directly correlates with the number of tests that can be run.

Dr. Amy Manning-Boğ
So you mentioned a broad range of climates there.

Jennifer Stone, MS
Sure. So, we’ve seen devices deployed to South America remote regions there. We’ve also seen them deployed in Africa, for example, the Ebola pandemic. Oh, yes. These are typically being deployed to very remote settings. So that could be rural communities, any place that’s a public health emergency or a combat zone, and also with a large pandemic, that really changes where field deployed devices can be used because in those situations there’s a need for test sites outside clinical settings to expand the testing bandwidth and community involvement even in highly developed countries.

Dr. Amy Manning-Boğ
So this is really interesting to me because I’m thinking beyond human health here, because you’re talking about access. 

Jennifer Stone, MS
Yes, that’s a good point. 

Dr. Amy Manning-Boğ
Do you see where I’m going with this? I’m thinking…

Jennifer Stone, MS
Absolutely. 

Dr. Amy Manning-Boğ
This is applicable to agriculture. 

Jennifer Stone, MS
Definitely agriculture, whether it’s animals or plant pathogens, being able to take that device to the farm or wherever that concern is, versus trying to collect samples and bring it back to the lab can really save you on turnaround time and cost.

Dr. Amy Manning-Boğ
Most of these tests are binary, yes/no, but if there’s rapid time to answer, then one could use this, for example, to screen a herd.

Jennifer Stone, MS
Yeah, so there’s a couple ways that that can be done. One is instead of testing individual animals, you can test something that will give you an idea of the entire herd’s condition. That might be something that does aerosol collection. We’ve also seen situations where people might be testing like chew ropes at a pig farm. Oh, clever. Yeah, yeah. Anything where a lot of the animals are leaving their material behind. You could do stool. There’s a lot of ways that you could tackle that from a perspective of looking at the whole herd health versus individual animals. 

Dr. Amy Manning-Boğ
Sentinel testing. 

Jennifer Stone, MS
Exactly.

Dr. Amy Manning-Boğ
When seeking detection and diagnoses, scientists have most often looked at the genetics of a disease. Today they can reference biomarkers, which can facilitate accurate detection to indicate the presence of a disease.

Jennifer Stone, MS
So genetics-based diagnostics involve direct detection of the pathogen DNA and RNA. Whereas with biomarkers, you’re looking for indirect detection, whether it’s a protein marker, an mRNA marker, anything that gives you an indication that the disease is there without direct detection of the genetics. Oftentimes that’s like an immune response of the human body to that pathogen being present.

Dr. Amy Manning-Boğ
How specific are those biomarkers for different pathogens?

Jennifer Stone, MS
They’re getting more and more specific. Now that we have machine learning and AI, it takes a little bit more work. Honestly, their non specificity can be a good thing in some cases.

Dr. Amy Manning-Boğ
Why is that? 

Jennifer Stone, MS
Yeah, they can be more universal and answer a specific question. For example, is the disease bacterial, viral, or fungal? And a lot of cases, that’s really what the clinician wants to know so that they know whether they should be treating with antibiotics or antivirals, antifungals, etc. It may not matter what the exact disease is. What’s important is what type it is and how it should be treated.

Dr. Amy Manning-Boğ
That’s a very interesting benefit of using biomarkers. Even ones that may not be specific to the pathogen, what are some other benefits?

Jennifer Stone, MS
So they can be more sensitive. For example, in bacterial sepsis, there’s often less than one bacterial cell per mil of blood. So when you’re talking about genetics based diagnostics, that’s a very small needle and a very, very big haystack.

Dr. Amy Manning-Boğ
Exactly. The analogy I was thinking.

Jennifer Stone, MS
Exactly, yes. And so when you use biomarker based detection instead and you’re looking for the host response to that bacteria being there, that can be prevalent at much higher levels than the bacteria itself.

Dr. Amy Manning-Boğ
It’s amplified. 

Jennifer Stone, MS
Another thing related to having a potentially higher sensitivity is that more sensitivity often translates to earlier diagnosis, possibly before symptoms are even present.

Dr. Amy Manning-Boğ
Oh, and that helps outcome.

Jennifer Stone, MS
Yes, definitely. Also, biomarkers have more applications than just detection. They can answer not only what you have, but how bad it is and what treatment is best.

Dr. Amy Manning-Boğ
Jen, we’ve talked about using blood as the matrix. What other matrices have you worked with to help develop?

Jennifer Stone, MS
Just about everything? And it really depends on whether we’re talking about diagnosis or detection. On the diagnostic side, blood is common. Also, if it’s upper respiratory infections, you’re talking about things like nasal swabs, nasopharyngeal swabs, saliva has become more and more common because it’s very easy to collect and noninvasive.

When you’re talking about detection, the possibilities are endless. I’ve seen everything from bits of tissue to teeth from maybe cattle that have died. If you’re looking for anthrax, we’ve seen so many types of matrices. People just collect whatever they can. We also see soil samples, water samples. The possibilities are endless. Could be anything.

Dr. Amy Manning-Boğ
Jen, your energy today for this topic has been, dare I say, infectious. Sorry, okay. You’ve done some fascinating work. I’m curious to know about what you see as your most interesting project.

Jennifer Stone, MS
That’s really hard, Amy. There’s been so many – one that is more recent during the pandemic, we developed genotyping assays that could be run on a mobile platform. That means that they could be done in remote settings without access to sequencing capabilities, which is really the only other way to get genotyping information. But secondly, they could be used to screen patient samples to triage and prioritize which samples should be sequenced. And that was really important, especially during, let’s say the first wave of omicron when the hospitals were just flooded with specimens and had this huge backlog of samples to sequence.

I really think that this is going to revolutionize diagnostics in places that really need it. So, I think about in the U.S., we have pretty open access to diagnostics, and that’s not true of all places in the world. They really need something that is small, easy, rugged, that can be brought into the communities where they’re needed and countries that are less developed, and that’s why I’m so passionate about field forward diagnostics.