Erin Spain: This is Breakthroughs a podcast from Northwestern University Feinberg School of Medicine. I'm Erin Spain, executive editor of the Breakthroughs newsletter. An exciting new study at Northwestern and the Ann and Robert. H Lurie Children's Hospital of Chicago could soon change the way we care for babies in neonatal intensive care units. Right now when you walk into a NICU, one of the first things you hear is the beeping of machines and one of the first things you see our wires - wires everywhere. The babies are typically covered in wires connected to machines, monitoring their vital signs. They're essential but can damage fragile newborn skin, making diaper changes and feedings cumbersome and disrupting skin to skin snuggling that helps new parents and babies bond. Northwestern's John A. Rogers and Amy Paller have just published a study in the journal Science that shows how ultra thin electronic sensors developed in Roger's lab have the potential to make NICU wireless. They joined me here today to share more. Thank you so much both for being here.
John A. Rogers: Thanks for having me.
Amy Paller: Our pleasure.
Erin Spain: So you two are from two different worlds here at Northwestern. Amy, you are a pediatrician, you're a dermatologist, you're a physician scientist, you're also the chair of dermatology here at Northwestern and John, you're a pioneer in the field of bioelectronics with an appointment at the medical school as well. How did you two come together to tackle this problem of wires and the NICU?
Amy Paller: Well, I reached out originally to a colleague of John's having learned about the flexible electronics in a Northwestern publication. That began a great excitement about the potential value of these devices both for hospital based use and also for outpatient medicine. We started out more than five years ago now on a project that looked at use of these devices to monitor wound healing and its potential complications after simple skin surgeries and advanced from there. It was shortly thereafter that I happened to be at a national meeting on investigative skin research where John was giving a talk and happened to show a picture of the potential use for monitoring in newborns. I got excited, reached out and the rest is history.
Erin Spain: A little background, John, this is your world creating these sensors these devices. Tell us about what you do in your lab and how you brought this into the NICU.
John A. Rogers: Yeah, so you know, this is an area of research that we've been interested in probably for about 10 years. Really initiated by just open ended kind of academic curiosity around what would be required from the same point of material science and electrical engineering and reformulating classes of electronic devices that exist in the consumer world to be biocompatible, to allow intimate interfaces with the human body and the skin is certainly an interesting starting point in that context because it's the largest organ in the body. It's a, it's a great place for noninvasive interfacing of electronics where the skin can act as a window for precise clinical grade measurements of underlying physiological activity. So really an attempt to move qualitatively away from kind of the rigid loosely coupled devices that currently dominate wearable technology into technologies that look a lot more like skin itself. So very thin, soft, compliant electronic systems that can softly laminate on the surface of the epidermis to record underlying body processes, vital signs, for example, with data streams that are sort of actionable from the standpoint of a physician. So moving from qualitative measurements of step count, for example, to ECG recordings with clinical grade quality. So that's been something we've been interested in for for a long time. There are a lot of kind of interesting questions around the material science that you would need to develop for that class of technology. We're engineers and that's the perspective that we bring, but ultimately in order to have impact, we really need to be collaborating with clinical folks who understand the use cases. That's where this collaboration with Amy and several others in Feinberg and Lurie has been so fruitful for us.
Erin Spain: And before Amy approached you after that national meeting had you thought about bringing a device like this into the NICU?
John A. Rogers: We've thought about it but just in a vague sort of engineering oriented way. I think we were aware of the kind of wired based systems that are needed in NICUs and the hazards and the deficiencies associated with that approach and so it seemed like a good match. But in order to do anything in a realistic or impactful level you really have to team up with the experts. I think Amy's base of knowledge around skin combined with the neonatologist and the pediatricians that we've been working with here at Feinberg and Lurie have resulted in a really powerful interdisciplinary team that spans the entire base of knowledge to make this really happen.
Erin Spain: Amy, take us into the NICU What does it look like in there when you walk in, what do you see?
Amy Paller: Well, the NICU is a very complicated place filled with very sick babies. Many of them born prematurely. So they're very delicate and I could say, let's go John, let's just get this project done. But it's, it's not so simple. It really took a lot of effort to get people together. The neonatologist obviously had to be involved. There are other pediatricians who are part of this process, lots of nurses and nursing directors as well as other research personnel who had to sit down, figure out how to move forward, get institutional review that allowed us to be able to move forward, get an initial grant and now we've been in the NICU, the neonatal intensive care unit, for about two years moving this project forward.
Erin Spain: It's important to note, these babies that are a part of the study, they still have the traditional wires on their body, but they also have John's device on their body as well.
Amy Paller: Absolutely. We must make sure that we're doing everything very safely with these babies and you have to test these new devices against the traditional wire device. It's important to have both on at the same time and this can be challenging, particularly when we're talking about young premature babies who don't have very much surface area.
Erin Spain: Well, John tell me about that. These are pretty small devices. How does the device work? How does the patient data record it and display it to the medical team?
John A. Rogers: Yeah, so the device, you can really think about it as a very thin sheet of silicone rubber essentially. That's kind of the mechanics and the physical form factor that we're talking about here. Of course, it's fully embedded with advanced wireless data communication, hardware, sensor suites and computational capabilities as well, but from the standpoint of the tactile feel and the physical experience, it is really like a thin piece of latex. I means it's stretchable like a rubber band. It can softly and non-invasively interface with even the very fragile skin that you encounter in these premature babies. From a physical properties standpoint that's the way you can kind of think about it. From the electronic and measurement standpoint it really, fully reproduces everything that is currently done with hardwired based sensors that connect external boxes of electronics. So all the data is streaming wirelessly and continuously to a tablet, a computer, for which we've designed software that allows a graphical user interface that almost perfectly replicates what the nurses are used to seeing in the NICU today. At this point the devices are still made in our labs, but the nurses and the other attending physicians in the NICU can operate the devices, record the data, understand what's going on completely independent of us. So that was kind of an important milestone in the process of trying to sort of mature the technology out of the academic lab, kind of into a form that can have real clinical impact.
Erin Spain: And there is also a transmitter that's involved, that's placed under the mattress of the patient?
John A. Rogers: That's right. The platform that's the focus of this particular paper operates in a completely battery free modality. Getting the battery out of the system was important for us in terms of achieving this kind of skin like form factor the battery sort of disrupts that in terms of the size and the bulk and the weight of the power supply. So instead we use a transmission antenna that's placed in proximity to the baby typically underneath the mattress of the isolette and that antenna is continuously in wireless delivering power to the devices that allow the operation of the sensors and the radio communication length its continuously wirelessly streaming data back to that same antenna, which is then connected to this tablet computer that's doing all the data recording.
Erin Spain: Amy, of course, you're very worried about these patients. As you've said, these are some of the most fragile babies at Lurie Children's hospital. Did they experience any side effects by being part of this study?
Amy Paller: I'm delighted to say that we really haven't seen any kind of side effects at all. Now it's important to step back and realize that sick babies tend to have more issues with their skin and with shearing. In addition, as we go down in gestational age, we see more and more fragility of the skin and when we're talking about multiple sites on the body that have these leads collecting information with wires attached, one of the big problems has been shearing of skin. About 40% of these babies in the neonatal ICU come away with scars related to devices and sometimes even infections occurring as well. So it's important to recognize that this was something that we were very worried about, especially as you're getting to under 32 weeks gestational age. We know that the skin starts to be very thin. In fact, 40% thinner than full term babies. In the first few weeks of life that skin matures and gets to the point where it's less fragile, but during that early period it's very important that we keep an eye on it. We have been serving parents and we've also been doing surveys of the integrity of skin with these devices. Looks great. No problems.
Erin Spain: Well that's another important thing to note about the device it's see through so you can sort of see through to if the skin is getting red or irritated, which is not something you can do with a traditional leads.
Amy Paller: That's correct and we are talking about a much smaller surface area. We don't have multiple leads. We have one at the center of the chest and then we've got one wrapped around the foot.
Erin Spain: So tackling an issue such as this requires so many approvals as you mentioned, just being in the NICU, collaboration from nurses, doctors, of course parents, but most of the parents you encountered really didn't mind being a part of this study?
Amy Paller: No, this is really quite an effort. Every morning there's rounding their decisions on which babies are stable enough to potentially be in the study and then to talk to the parents. Now, some parents are very worried about any kind of a study, but for the most part this has been embraced by parents. And the feedback that we've gotten after parents have been involved with this study with their babies has been uniformly positive. They love the idea of getting rid of the wires. They love the idea of being able to hold the baby and have that skin to skin contact that we know is not just wonderful for bonding, but also lowers the risk of lung and liver and infectious issues in these neonates.
Erin Spain: Well, explain that to me. So right now, when a parent pulls the baby out of the isolette they want to hold and cuddle the baby, what is that experience like?
Amy Paller: You really can't do that very easily when babies are covered with wires and basically tethered to a bed. It's hard enough just to even be able to turn these babies. They can't get very far from the bed either, as you can imagine, to even sit in a chair. I was talking to one mother the other day who said, "I want to breastfeed, but I can't get far enough away to sit down and be comfortable". Imagine if you didn't have those wires. It becomes a possibility.
Erin Spain: Let's hear from one of those parents whose child is enrolled in this study.
Tashanna Taylor: Hi. My name is Tashanna Taylor. This is Grace Reigns Taylor. Her name literally means she reigns her father. So it's Grace Reigns Taylor. Trying to feed her, change her, swaddle her, hold her, move around with her with the wires was a little contained cause we have like a three foot radius to be with her. We were really excited about the wireless. In theory, if she didn't have the wires on her, maybe we can go for a walk around the the room or, you know, the area. Maybe we could probably spend a night upstairs together. You know, it would just make the entire experience more enjoyable and more bonding with her.
Erin Spain: John, as you mentioned before, you took special care and the interface that's used for the nurses. Just interpret the vital signs coming in. How important are nurses to this study?
John A. Rogers: Well, they might be the most important people actually because they have the deepest insights into what works and what doesn't work. Operationally, you know in NICU and so we collaborate very closely with the nurses at Luri and take all of their feedback very seriously and embed their suggestions directly into the engineering platforms. I would also say that even before we got this technology into the NICU there's tremendous amount of scrutiny around the design of the devices, the materials, compositions, the RF radiation that's involved with their operation, the wireless links to make sure there aren't any unwanted interferences with other kinds of instrumentation that already exists in the NICU. I think it was a 12 to 18 month process just to get the approvals in place. I think that scrutiny is fully warranted. So we had a chance to interact with not only the nurses, neonatologists, the pediatricians, the attending physicians, the entire collection of folks there to make sure that what we were developing was going to be compatible with that very challenging environment. I think you could argue that these premature babies are probably the most precious asset in the whole hospital, right? So everybody's looking at all of the details very carefully. As Amy mentioned, we haven't had any adverse events and I think that doesn't happen by chance. Right. There's tremendous attention to what's going on here and that's a very important part of it.
Erin Spain: And a lot of these babies were monitored for 24 hours. Out of the particular baby is mentioned in the study that was published in Science, how many children were involved with that?
John A. Rogers: Oh, a few dozen. The science paper is actually, by now, some months old relative to where we are right now. Just do the review process and so on. So these studies are fully ongoing. We have weekly meetings. It's a broader team consisting of engineers at Mccormick and physicians at Feinberg and Lurie. It's dozens of people literally. We have these weekly calls and we're consenting babies and we're mounting devices and refining things and improving the technology out, but done in an incredibly careful systematic way to make sure that everything is operating in a safe manner.
Erin Spain: Another interesting part of the technology I want you to tell me is that besides being wireless, there's properties of this device that make it really suited to the NICU. For example, it can go into an MRI imaging situation.
John A. Rogers: Yeah, so there were a number of different design targets, right? One of them has to do with mechanics and form factor in weight and thickness and thermal mass and all these kinds of properties where the goal was to match the physical characteristics of the platform. Precisely to the skin itself. So it's almost like a second skin just gently interfacing with the actual skin. And that's all about mechanical engineering and material science and we work very closely with collaborators in mechanical engineering to do full blown numerical precise simulations of the mechanics. We sort of optimize the configurations. Obviously, the electrical engineering aspects are important we are operating battery free. It has to have high fidelity in the data streaming. The precision of the operation of the electronics has to be there. There's also active processing on the data that's happening in the patch itself. There's some level of data analytics that are sort of programmed into the electronics. So there's an aspect of computer science and computer programming that they go in into the device. But as you mentioned, we've also paid a lot of attention to the electromagnetic characteristics of the system. They're naturally transparent to visible radiation just due to the open mesh architecture and the transparent silicone materials that we're using to build the devices. But as you mentioned, having these devices radio translucent at the level of x, ray imaging and MRI imaging also turn out to be very important. So designing configurations of these devices to allow x rays to be performed without needing to remove the device to allow MRI images to be acquired also directly through the device. You know, what was an additional important part of the engineering efforts is really highlighted in the paper as well.
Erin Spain: Amy, as a physician scientist hearing about this sort of advance - how does that make you feel? When patient care is the bottom line for you - improving patient care. Now there might be an opportunity to better care for these small children.
Amy Paller: It's tremendously exciting. The access for doctors is also going to be dramatically improved and that's always been an issue. Now we can see more of the baby, we can get to the baby more readily. Being able to just keep on these monitors even while the baby's bathing. John, you might want to mention too that you can get these wet and it's okay. To be able to do all kinds of things that are now somewhat curtailed by having a baby that's just covered with wires is revolutionary.
John A. Rogers: Yeah, so the devices are encapsulated in a way that makes them waterproof. The kinds of radio transmission frequencies that we're using are compatible with biofluids in water. They're not, you know, disrupted by that kind of thing. They are quite robust in that sense. I think an additional consideration here and so I think the science paper is great. We hope that's the starting point, not the ending point. Obviously we want to see this deployed at scale. Issues of cost really matter here. I think ultimately we would like this type of solution to be much lower in cost than what's done today with these hardwired sensors and in large scale boxes of electronics. If you look at the parts cost and the materials costs associated with these devices, it looks to us like you can put them together for maybe $10, $15 or so. If you compare that cost of what's the gold standard of clinical care today, it's comparable to the leads themselves, which are used in a disposable manner. They're not reused. And so I think our vision is that these devices would be used once. They could be recycled, but you don't have to worry necessarily about sterilizing them to allow them to be reused. I think that's an important additional feature of the engineering. It also opens up opportunities for using these kinds of devices for the developing world where there aren't any monitors currently. So that's an important part of where we're going into the future as well.
Erin Spain: And that's a very real project that's happening right now. While most people may be hearing about this technology with the Science paper, you've spoken about this publicly in the past. You were actually approached by Bill Gates. Tell me about that and what you're doing with his foundation to deploy this into other countries.
John A. Rogers: Yeah, so that was an interesting interaction. The Gates Foundation has been very active in issues around global health and global challenges in health. Primarily from the standpoint of drugs and vaccines and pharmaceuticals and I think the foundation, I wouldn't want to speak for the foundation, but my understanding is that they're developing a deeper interest in technologies that could be companions to vaccines or drugs or stand alone pieces of technology that they could lead to improvements in health status in the developing world. I was invited along with a very small other collection of speakers to present directly to Bill Gates in September, 2017. I had a chance to meet Bill and his entourage and gave a talk on this stuff and brought some of the devices. After the presentation I was able to convince him to try one out. He actually wore one of the devices. I've got a picture of Bill Gates wearing a device - it is on my phone - one of my most proud and precious photos on my phone. I think that that interaction served as a nucleation point for what is now a funded program through the Gates Foundation and the Save the Children Foundation to distribute these devices into the developing world: India, Pakistan and Zambia in particular. The target, and we're on track for this, is to deploy 20,000 units into those three countries through 2019 using support from the Gates Foundation and the Save the Children Foundation. It Is very exciting.
Erin Spain: These will be going out on an experimental basis, they are still an experimental device, but the potential is there to really make some big changes in those countries.
John A. Rogers: Yeah. It really allows us to exercise the manufacturing flows and demonstrate robustness for operation and those kinds of environments. We'll be working closely with the folks at Gates to understand analytics around the data to develop deeper insights into what these measurements are saying about the health of the babies. It's a tremendous opportunity to take the technology to the next level.
Amy Paller: I think that it should be emphasized that these devices have tremendous values beyond the neonatal intensive care unit. That may be where it started, but this has moved now into the pediatric intensive care unit, into the cardiac intensive care units for these babies and older children as well and can also move into the adult world of the hospital and beyond. We're very excited about some new developments as well, taking this kind of device into other realms. For example, in the world of dermatology itch is a major problem and at this point we have very few objective ways to determine how much a patient is itching. We rely merely on the patient's interpretation of the level of itchiness. Now there are devices that John and his team are developing that allow us not just to determine how much movement there is that simulates itch, but actually to distinguish that allow us to determine movement versus scratching versus rubbing using mechano acoustic sensors. We're just thrilled about being able to take this into trials and potentially deploy this as an outpatient measure that patients can take home that goes along with trying new medications so the doctors actually know how much things are helping with patient itch.
Erin Spain: Yeah. It sounds like these devices really are a perfect match for skin and medicine.
Amy Paller: Not just skin in medicine, but really throughout the realm of different disorders in medicine not just collection of vital signs. John can address a few of the other directions that this is going, but it's really truly going to transform care both inpatient and outpatient.
John A. Rogers: Yeah, I think we have 26 IRB approved human clinical studies of these classes of devices across a very broad range of conditions at the medical complex downtown Feinberg, Shirley Ryan Ability Lab, Lurie Prentice, and so on. It is very exciting that sense. Gates is interested not only neonatal health, but also maternal and fetal. The devices that we'll be deploying through that program will also involve measuring the mother's health and the health of the fetus both before birth. I would also make a comment about Northwestern itself. In this context, to our knowledge, there are no programs like these anywhere else across other universities in the US and I think it's happening at Northwestern because we have a tremendously collegial and collaborative set of faculty both in engineering and in medicine and we have a unique center. The center for bio integrated electronics that's really bringing together medicine and engineering and in really new ways. I think the interface between those two disciplines is a very fruitful one. For research and development and ultimately for the launch of new technologies that can reduce the cost and improve the efficacy of healthcare. So really special entity and it's been supported with philanthropy from some of the trustees here at Northwestern, Louis Simpson and Kimberly Querrey A lot of this stuff just wouldn't be happening absent. That center is very important.
Erin Spain: These are becoming reality. This study is sort of the proof of concept. The first look at that it can work, but this is going to be going through FDA approval. Where are we at right now with that one? When might we see these devices out on the market and being used in hospitals?
Amy Paller: Well we still have some work to do. We've now got about 50 babies who've had monitoring for at least 24 hours. It's important to continue these studies to make that longer periods of time, show that perfect correlation between the wired devices and these wireless devices. It's also important that we really get into the very young gestational age babies. We've gone down to 28 weeks, now we're going down further and we will make sure that these devices are very safe with respect to this very fragile skin of these babies.
John A. Rogers: Yeah. We've started to look very carefully at the detailed requirements around that approval process and establishing quantitative correlations to predicate systems. The hardwired your devices is certainly the first and most important step in that process. But we're thinking it's kind of on the order of a two year type of activity to get these approved and that's very much a target around what we're doing.
Erin Spain: Then maybe there could be technology where parents could take the child home wearing a sensor and monitor in conjunction with their physician themselves.
Amy Paller: That is the goal.
Erin Spain: A note for physicians who listen to this program, you can now claim continuing medical education credit just by listening to this podcast. Go to our website, feinberg.northwestern.edu and search for "CME" for more details.