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>> Good one of those. 3 right for a good time and you're right when you're right and back then I'm not buying from you were whipped up beating on I mean clearly you are full and complete certain never intended. Where you are or you can be involved for Obama where.

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You know how do you come home and think I'm perfect. If the only people there are almost no longer and we don't need them to not look at nobody home. And refer you back you know you are handed over to me my good rather than I might lie and you know a word or I'm right.

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Into it and it wants. Ok Well thank you very much for that introduction and thank you young men for hosting me today so I'm looking forward to the rest of my visits and chats with students and faculty have a lot of connections to Georgia Tech so it's always fun to to visit.

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Take the next you know 45 minutes or so to talk to you about some things that we've been doing in an area of research that kind of has nanotechnology underpinnings but really extends into the domain of biomedical engineering biotechnology so it's really kind of the interface between materials science and medicine in a sense in the title as was mentioned as semiconductor nanomaterials for trends in electronics is kind of a funny area but one that we've been thinking about in an area that we've been working in for the last 7 or 8 years and I think we're beginning to develop some momentum and other groups are active in this area now as well to the point that we can now begin to envision devices that could have potential utility in human health care and that's that's very exciting for us because ultimately we're thinking about not just the academic research you know interest but but ways that to have broader impact and so I'll start by kind of motivating you know our activities in this area give you a perspective of what transit electronics is relative to other systems that you may be more familiar with provide some context and then step you through some ideas of material science and electrical engineering device design that have worked pretty well for us over time and then kind of terminate with a discussion of system level in body months of these ideas that you know have the potential to address unmet clinical needs and so I said it's very much kind of research at the interface between engineering and medicine which I think is a very.

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Full space for academic activity and as a result it's highly interdisciplinary So my own home department my core expertise is in electronic materials science but we have students and postdocs from various areas of engineering and we have deep ties into the medical community as well so departments materials science and engineering but I actually have a real appointment in the medical school of neurological surgery so you never want me to do a surgery on you but we have a lot of collaborators in that department in across the medical community in Chicago and I'll try to give you a flavor for how we think transience electronics may fit into that broader landscape so ultimately what we're interested in is developing materials and devices that will allow intimate integration with biological systems with Target on humans ultimately but but where there also are areas of utility for advanced animal studies of basic biological processes so tools that will provide new insights into the underlying principles and science around living systems but then also you know with this orientation around biomedical engineering for for human health care and you think about semiconductor devices an active electronics in general I think it's easiest to think about that in the context of the human brain which is you're probably the universe's most sophisticated system certainly biology is the most sophisticated computing system and if you understand how the brain works and that's a from Syria area of science in itself or if you want to develop engineering approaches to dealing with brain disorders such as Parkinson's and Alzheimer's you might want to bring to bear on this systems man's most sophisticated form of electronics like the silicon integrated circuit something with that level of sophistication to allow you know a kind of interface that that could have impact the 0 in those in those 2 ways but then if you think about you know electronics as it exists today typically supported by a semiconductor wafer you know the mechanics and the and the geometries in many cases the underlying materials are fundamentally.

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Incompatible with a soft curvilinear time dynamic surface like that of the brain and so the material science challenge becomes around how you you develop a collection of electronic materials that allow you to build those kind of semiconductor systems in form factors that look like biology so soft tissue like devices for integration of the brain but other areas that might be of interest integration with the heart the spinal cord the purple nervous system the bladder the skin lots of different inner pace face points would open up if you could create sort of this biocompatible class of electronics and that's been kind of a motivating father around our research for the last 15 years or so and so it's a broad range of opportunities there but those that you know could have again this kind of broader societal significance so at Northwestern we have a center that sort of supports activities brings clinicians together with folks in the engineering school and this is a key mechanism by which we're able to move move forward in this space is the center for bio integrated electronics instrument in that So if you think about integrating sim conductor devices with biology it's useful to think about what are the underlying design principles that you see in biology not with the notion that you're going to replicate one to one those kinds of design approaches in a manmade system but but just kind of features that are useful to keep in mind when you think about your bio compatible Microsystems' and bio integration and so this isn't a you know a list that's that's too terribly insightful but it's just kind of a reminder of things you probably already know if you think about biology it's an incredible range of length scales active systems that have characteristic dimensions from a few nanometers to meters these are intrinsically 3 dimensional in their form of integration it's hard hard materials integrated intimately with soft materials they're reconfigurable and responsive and dynamic just spectacular levels of sophistication and how could you sort of adapt or abstract some of those concepts and embed them into electronic systems.

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Comes kind of an interesting question too to kind of contemplate so in the broader context of bio integrated systems we have you know within the group and within the center kind of 3 separate streams of work one is around the development of soft tissue like electronics which I looted to before then membranes essentially that can softly and intimately establish contact with soft tissue systems the skin being an example but as I mean to the brain and heart as well for doing sensing or for delivering therapy to to that interface you know in a chronically stable sort of configuration so bridging sort of the the divide between mechanics and geometry and materials that you know are currently available in commercialized electronics and and what you see in biology is that that's the main thrust of our work the other is to think about devices that are physically time dynamic or trends in and since again you know biology is characterized by a turnover of time time dynamic you know intrinsic feature of the systems can you build devices that you know would be defined uniquely by an ability to resorb into the body over time and so you can think about electronics in that context that could be brought to bear to a wound site for example and as the wound is healing it could provide syncing and actuation functionality relative relevant to the hearing process but then after the wound is healed you don't need the device anymore could you created out of materials that would naturally disappear the 0 and eliminate themselves thereby removing what at that point would be unnecessary device load on the patient and this is what I'll talk about mainly today but I'll start with a little bit of context here because it makes the transition a little bit more smooth and allow you to sort understand what the motivations are here and then the 3rd area is thinking about extending kind of planar systems sheets like these and inflexible devices like these into the 3rd dimension because biology is intrinsically 33 dimensional and could you think about 3 dimensional.

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Open Architecture that allow you to integrate with biology over 3 d. volumetric spaces rather than just on surfaces and this is still a little bit exploratory for us but I think we now have some approaches that allow us to build these kind of 3 d. architectures Rimmon is than of neural networks in the brain or vascular trees that you see or even side of skeletons at the level of the individual cells so that's kind of a broad overview of how we're thinking about things in all of those areas you have to come up with sort of new material strategies to you know support the active components because again an immediate use of a way for base technology in the context of those kinds of systems is not going to be all that relevant there are all that useful so you can think about 2 different strategies one would be to reinvent an entirely new class of electronic materials move away from inorganic semiconductors like silicon gallium arsenide gallium nitride to move toward polymer based materials polymer semiconductors or carbon nanotubes or graphing we've spent a lot of time exploring that route to biocompatible electronics and there are a lot of groups doing great work in that space and I think it's still a very rich area for academic discovery but the other way to think about it would be let's stick with the known materials that already serve as the underpinnings for commercialized devices but instead of the playing those materials and macro scale forms like semiconductor wafers think about what nanotechnology and nano scale forms of material could bring to bear in terms of alternative form factors and so one approach that's worked really well for us is to use nano scale material elements of.

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Substances light like silicon they're already well known in wafer bait based form but whose job it can exchange is in an important way as the dimensions are reduced and so this is sort of just elementary bending mechanics but it turns out to be sort of important so the bending stiffness of materials the fine.

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Not only by the intrinsic mechanical properties that materially Young's modulus but also depends on say the cube of the thickness for a slab or sheet of material and so in going from a way for where the thickness might be you know in the range of a millimeter or so to sheets of the same material that have thicknesses you know some orders of magnitude smaller maybe 10 nanometers or 100 meters ginned up with many orders of magnitude reduction in bending stiffness because of that cubic dependent so if you think about silica nano membranes are very very flexible you can bend them to very tight radius of curvature because the peak strains associated with been doing scale down linearly with the thickness so you know with a very flexible floppy piece of material now it's not a one to one replacement for the wafer but you can think about this kind of construct as a building block material that you can integrate with the substrate that would give you the mechanics that you ultimately want so the teacher plastic or a slab of rubber for example and so in order to do that you have to think about how do I heterogeneous we integrate in inorganic a low c.t.e. material like silicon with a polymer based you know substrate like Poly and much different in terms of mechanical properties and coefficients of thermal expansion and if you think about just gluing a silicon wafer chip onto a piece of plastic you realize that that is and he's of interface it's very hard to manage from a practical standpoint how do you get strong enough that he's in to maintain bonding and there are you know the thickness reduction comes to your rescue again in terms of the scaling parameters of the energy release rate parameter g. which defines the proper pins city of a crack to form between 2 dissimilar materials it decreases linearly with thickness so as you go from a silicon wafer scale piece of material to one of these nano membranes it comes easier and easier to stablish a robust bond to a dissimilar material like a plastic or rubber and so that's just an example of that this is a piece of silicon here just by the inner walls forces to a micro machined Ridge on an underlying plastic substrate and you.

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Sort of maintain the structure and that can be leveraged geometry partly because of that linearity reduction in the energy release rate associate with fracture of that interface with thickness the linear decrease with thickness so those are 2 really really basic ideas in mechanics that that make nano scale forms of materials like silicon or gallium arsenide the same considerations would it would apply begin to make those costs the materials are interesting in this broader context of integration so then the next question is if that's what you want to do from a mechanic standpoint how do you create the material elements in the 1st place and one way would be to develop new growth techniques for silicon and there's been a lot of work obviously in silicon nanowires and so on and that's certainly a promising way to think about you know forming these elements but then at the same time you have to recognize that the silicon wafer itself is a commodity piece of materials technology very very sophisticated but low in cost because it's been driven to that low cost point by this you know huge industry of consumer gadgetry and so if you could think about using that material structure as a starting point that might be an alternative way to think of Korea think about creating these nanostructures So it turns out there and isotropic etching tricks and all you take away for and then shave off very very thin nano scale ribbons of device grade model Crystal and silicon from the New York surface region of that wafer and you can do this multiple times this is a chain of a silicon wafer with a 111 orientation so you can kind of do this we stop the action in this case just before it completely undercut the ribbon but the but this turns out to be a very nice way to create high quality you know pieces of material with these nano scale forms and there are ways you can get tricky about this you can sculpt the sidewalls you can evaporate using directional flux metal as a as a resist layer on this on the side walls leaving just certain regions of the silicon exposed you dump that into chaos.

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And you can create you know Bolt. Quantities of silicon and ribbons just in a single process sequence so that works pretty well there are other kinds of approaches you can apply to compound semiconductors not just silicon there and isotropic etching tricks that you can use with gallium arsenide for example to pinch off the near surface region in this case triangular cross-section gallium arsenide wires again you know the been doing mechanics being defined by those characteristic.

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Dimensions which Here are some sub micron in terms of scale so silicon gallium arsenide similar ideas you can do in the fast 5 gallon nitrite you can create a whole portfolio of similar nanomaterials starting with wafer based forms of these materials and it turns out to be very straightforward method that doesn't require reinvention of growth techniques to create these women so then the 3rd question is how you get to move these materials around so that you can integrate them in a deterministic way into a real working system and there's been a lot of work on sort of self-assembly approaches fluidic guided you know shaped complementarity in substrates and you get sedimentation all kinds of different ways to think about how to organize wires you know I think you have to really consider you know in a serious way through puts and yields and and orientation control positional control and so we've taken a different strategy which is one that's inspired by the ideas of the software far graffiti where you're not printing molecules you're printing semiconductor nanostructures and because they're generated from a way for using the lithographic process you know exactly where those membranes are ribbons are located initially you can take a stamp and then use that pre-processed way for almost a can inking Pad bring the stamp in the contact list that often end up with ink regions of the raised features of relief on the stamp and then use that index the stamp over target substrate and then you can deliver these material elements down in a very highly controlled high throughput manner so you can print you.

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Hundreds of thousands of individual nano ribbons or membranes in a single per print cycle and then you can step in repeat and move material from a relatively small area that defined by the way for size to very large areas across the substrate of interest in the key here is control of the mechanics of soft and he's And because you can imagine you want a very strong adhesive force to allow you to lift these elements from the way for very high yields but you don't want the it to be so strong you can't get them back off the surface of the stamp so there's a whole set of research concepts that we've built out over the years that allow you to switch that he should from strong to weak to allow this process to happen at very high yield so he won't go through that sort of outside of the scope of the talk today but you can build tools around that and these are used in high volume and you factoring in micro scale displays by Excel a print and x. display and and others so basically an automated system you have a vision camera that allows you to do registration and overlay and and stages allow you to move move the substrate around to do this printing in an automated fashion but you say you can take all those ideas mechanics materials manufacturing and then bring them together to allow for the construction of very high performance flexible electronics this is an example of very tiny micro scale l.e.d.s. and Gap $600.00 of them a 100 percent you know about 200 microns and aside 200 meters and thickness printed onto a sheet of p.t. and then subsequently wrapped around a cylindrical support just give you a sense of the building mechanics which really relies on the principles I described before our gap is a very very brittle material yet in these very thin small forms you know they can be bent you know to this kind of radius of curvature and they don't pop off the surface because of that linear downscaling of energy release rate with thickness so it's kind of an illustration of all the ideas sort of put together in a way that kind of visually illustrates those concepts so if this is a capability now you can imagine.

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Building electrodes and interconnects and dielectric layers and starting with these high performance electronic materials in a flexible substrate you can now build out your biocompatible but still very high performance materials that are leveraging you know all the progress that's been made around conventional electronics but adapting those materials and ideas in in a direction allows you to achieve qualitatively differentiated mechanics so you can do this kind of things you can build skin like devices that can interface directly with the epidermis you can exploit that skin interface for measurement of clinical grade quantities around physiological health and you do continuously and wirelessly so you can do for example going far beyond what is possible with a conventional wrist mounted wearable that's the idea of skin like device exploiting that skin interface to reproduce kinds of measurements that done in a hospital but in the real world continuously so we sort of felt like we had figured this out 2011 got a lot better at it in 2014 and from that point on really focused on how do we take all these ideas and material science and mechanics and bio integration and so on to do useful things and one of those things is the development of purely wireless ways to do full vital signs monitoring of probably the most fragile patients that you'll encounter in any kind of hospital complex of premature babies and so they're typically monitored by wired based systems that have to be adhered to the surface of the skin with tapes that can sometimes cause skin injuries upon removal because the skin is highly underdeveloped in these babies and being able in the future to get rid of the tapes.

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You know surface interface wired based electrodes and replace them with sort of skin like devices operating wirelessly is something that you were very interested in and I won't go through the details you just published a few few months ago but this is full the point of all those kind of ideas in probably the most demanding area of the hospital the neonatal intensive care unit and so deep into that into that process where in the neonatal i.c.u. but also the.

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Pediatric i.c.u. at this point so we've broadened beyond neonates into pediatric population ears lightly larger babies but they still require 247 monitoring of all vital signs and you can reproduce those measurements with full clinical grade quality now with skin like devices one on the chest and one on the foot and they're operated in a battery free wireless manner wireless energy harvesting coming from an antenna that's transmitting at the base of the chair in this case up to the devices the same magnetic conductive link is allowing for data flow back back out so this is a major program for us going beyond just publishing papers we actually have to see angel funding now from the Gates Foundation the Save the Children Foundation to deploy these devices into the developing world where there are no monitoring technologies at all wired or otherwise and so we just launched into Zambia in Kenya this month so we've put a 1000 devices into both of those locations Zambia is mostly focused around maternal health Kenya's neonatal and will be going into India and Pakistan as well over the next 1212 months so we're doing $10000.00 units into that into that.

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Set of countries and I'll be in Zambia myself in December to see how things are going so this is the team just to give you a sense we sort of sort of put it all together building thousands of devices we have the full software interface and so. So that's kind of what's what's going on in terms of skin interface devices let me sort of transition to this idea of transition electronics was to be the main point of the talk before I do that I would just say that the same concepts I just outlined to you for skin like electronics as I mentioned at the beginning of the talk the broader motivation is bio integration not just skin integration so we're looking at brain and cardiac and spinal cord purple nerves and bladder are active areas for the group the same concepts applies so you can put electronics on the surface of the brain in ways that are fully conformal to the textures of the brain and you can establish long term interfaces the electrical interfaces of the brain for stimulation and monitoring of brain processes you can do the same thing in this case in a 3 d. matching form to the full epic surface so you can wrap electronics around the outside surface of the heart almost like an instrument of pericardium and that turns out to be pretty interesting as well our initial work in brain interface is motivated by the need for a high resolution diagnostic for measuring electrical activity in the context of a surgical procedure used to treat acute forms of epilepsy which involves 2 steps one is observing the patterns of electrical activity while the seizure is happening a train surgeon takes a look at that space show to a representation of the electrical activity identifies the this site of the brain that's causing that abnormality and then they come in and they respect that and the idea was to create a surgical diagnostic tool in that context of allow you to map out that spatial temporal distribution of electrical activity at resolution that's much higher than what's possible today with just passive allays arrays of electrodes so full integrate electronics as a diagnostic and in that case you need an interface to the brain that is stable over a time scale of a few days typically And so the device is just placed there a few days in it's removed and that's it so you can think about all kinds of surgical tools where the residents time the tissue interface really need.

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To be stable only for a relatively short short period of time at the other end of the spectrum in terms of application opportunities would be a replacement for a pacemaker just looking out into the future 1020 years into the future going beyond just a point contact electrode interface for pacing the heart to something that would allow for space yoga temple control of pacing voltages across the whole surface of the heart.

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To do more sophisticated militant if you lation that maybe provide syncing capabilities as well you could detect maybe the early onset of an arrhythmia and then stimulate the heart in a way that would eliminate that condition that kind of be the vision in the into the future but if you're thinking about that as a possibility now you have to think about resonance times that would be comparable to the life of the patient so now instead of a few days or a week you're talking about a few decades maybe 50 years 100 years and that creates a whole separate set of challenges around how you create material systems that are stable for that type of time scale when you're completely immersed in warm salt water right the surrounding bio fluids and so there's a lot of interesting materials science questions we're interested in both of those applications what we didn't realize back in 201-120-2012 or so is that there are a set of opportunities in the middle of those 2 length scales of time scales devices that you would put into the body and they would survive maybe for a few weeks.

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Where their operational life time is correlated and time to match a natural biological process or you can think about it in the context of like a resort suture So you suture up your skin a lot of times that suture thread is resorb so it would just naturally disappear as the wound is healed so you don't need to take the suture threads back out after they're no longer needed Can you think about that type of concept in the in the context of active electronics you might go inside the body for an internal wound and you could monitor the wound healing process maybe deliver therapies drugs electrical stimulation to it.

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Celebrate the rate of regeneration and then after the hearing is completed the device will just naturally dissolve and disappear into the body and so that was kind of the concept so you know this is the definition that we have used for the spaces trans in physically trans in electronics is defined by those that fully or partly do solver resorb or otherwise physically disappear at some kind of program greater triggered time and you can imagine there would be applications going beyond bio medical devices which I just described to you not only in the context of wound healing but maybe chemotherapy other kinds of you applications that have only a certain time window associated with them so temporary diagnostic implants that you think about even the same ideas in the context of consumer electronics where the transients in this case if you could think about sort of environmentally degradable materials that might be an interesting thing can to consider for products like r.f. id tags were huge numbers of tags you don't need them for long periods of time just sort of point of sale and maybe you could create those out of reserve of materials to eliminate the or reduce electronic waste streams in that in that case Survivorman a monitor sensors you deploy were funded by DARPA for a while of hardware secure Alectryon it's non-recoverable systems that could be triggered to disappear if they were at risk for recovery by an adversary or hardware reconfigurable systems as well so those are the kinds of opportunities I'll just talk about our interest here because that's the main motivation for our work in this area because think about it a little bit more broadly so as for these biocompatible electronic systems the big question is what are going to use for the materials here you have to think not only about mechanics but also about by resorting to delivery and you may again sort of naive Li be drawn towards polymers or maybe carbon nanotubes or small molecules of polymers may be attractive and they are attractive in principle because there's a tremendous amount of chemical versatility indeed in the way the you think about the power polymer.

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Mc chemistries but where you might be able to conceivably create a material that not only is excellent in terms of electronic properties it also has the ability to undergo hydrolysis for example and expose the water and there's a lot of work thinking about polymers in the context of trends in electronics but as before if you if you could figure out a way to use silicon for these kinds of applications that's what you would do because it's sort of the workhorse materials was already understood about silicon and how to manufacture with it and build high quality devices but you would not even I think again as maybe you would for flexible devices that silicon is not going to be relevant for trends in electronics because you know for people doing electronics you know you think about silicon mostly in the context of a silicon wafer and I think in terms of chemical stability most people consider silicon as sort of Iraq you know you put it in a bucket of water not nothing much is going to happen and it turns out that that is true but only to some degree it turns out that the silicon is in fact water soluble just at super low rates that you typically can ignore you know at the scale of a bulk piece of material like like a silicon wafer but if you're playing around with these very thin silicon nano ribbons and nano membranes like we were in the context of these flexible Bio Bio integrated systems those very slow rates of dissolution and water become very meaningful so you can take a very small platelet in this case it's a f.m. image the height is exaggerated about $100.00 nanometers and thickness a couple of microns on the side if you immerse that in a buffered solution sailing solution at physiological ph which is slightly basic physiological temperature you can just watch it disappear if it actually dissolves very slowly a few nanometers per day based on a surface erosion process but but it's completely gone you know in just 3 weeks and the chemistry is very similar to the chemistry associated with silicon micro machining from the Mims community but occur.

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During at a near neutral ph value so it's very very slow compared to silicon etching but it's essentially the same chemistry of silicon reacting with water to form solicits acid and a little bit of hydrogen and so this is very very interesting to us because you know we kind of stumbled across it didn't really think about silicon as a possible candidate for transience electronics but the this is was a great thing partly because silicon is already very well developed as an electronic material semiconductor material but also because solicit acid is naturally occurring in bio fluids so it can is a recommended part of a daily diet it's occurring in ground water and so it's biocompatible the end product is compatible and you only need a tiny amount of silicon in order to build active you know devices just microgram quantities so this is some.

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Simulations of that chemistry so this is a silicon Crystal here immersed in water you can see here at neutral ph in that particular silicon atom is tagged because during the course of this movie it will react with water and dissociate from the underlying crystal in the form of solicits acid so you can imagine if you continued this simulation you'd eventually consume that nano crystal of silicon so it was just sort of a study of the underlying chemistry and I won't go into the details who published several papers on on the chemistry of silicon dissolution and hydrolysis but that's kind of the essence of it so if you think about silicon for transit like Tron is the key is it's very very thin so that it can dissolve on a reasonable time scale so $35.00 nanometer thick layer of silicon which is used as the top device layer and silicon on insulator electronics consumer electronics if you think about that for trains in electronics it will dissolve it in 10 days of immersion in your sort of simulated bio fluids and you only need about half a mil leader of water to consume a one square centimeter area of $35.00 nanometer thick silicon without exceeding the solubility limits associated with slits gases so that's kind of how it works the silicon wafer just by point of comparison is nearly a millimeter thick and requires nearly a 1000 years to dissolve and for once the m² chip of silicon you need 8 leaders of water so this is conventional this is trans in this is something you could imagine eating or putting in your body this probably don't want to do that.

[00:32:35]
So that's the semiconductor and then we kind of went nuts you know early 20132014 building out a complete tool box of materials that you could add to silicon to begin to build devices that are entirely transience so silicon is great but various forms of silicon not just model crystal but amorphous nano porous germanium silicon germanium zinc oxide they're all water soluble semiconductors you can think about as I o. to silicon nitride these are great dielectrics they also dissolve Slezak acid is the reaction product for as I o 2 so it's a gas it an ammonia for silicon nitride And so this is great because these materials are already used commercially in standard device so that you think of other things magnesium oxides been on glasses there number of different metals you know about 4 electrodes interconnects wiring and so on we do a lot with magnesium and zinc but tungsten molybdenum iron and pace of these materials as well and then what are you going to build your devices on well there's a whole range of known biodegradable polymers you can think about for that purpose and you can use these materials as well for in capitalisation so here's an example of a paste built with tungsten and wax so you can build not only evaporated layers of metal that you can pattern using photo fogger fee but you can also screen print thick conductive material by using these kinds of these kinds of paste and you a lot lot of different materials ideas can be brought to bear to this area very straight straightforward So there's a lot of versatility that the key is that you can build high quality devices devices with performance that is comparable to a conventional way for base system but constructed with purely bio restore bable and cereals this is an example of an array of transistors that's the kind of mobility very good switching characteristics you can build a logic gates by putting multiple transistors together all of that works you can build strain gauges and so on again using Piazza resistive effects in silicon.

[00:34:34]
And I'll come back to this in a little bit and describe how we exploit that kind of syncing mode out in the context of traumatic brain injury and also do photo detectors solar cells different different things you can put it all together and build simple circuit so this is I r a fossil later the includes an inductor capacitor high speed transistor r.f. diode and a resistor where the constituent zeros are silicon ultrathin So a console can you know membrane silicon dioxide magnesium magnesium oxide and here it's silk fiber and is what we're using as the substrate so it's a copecks oscillator it operates like you would expect an oscillator to operate with this particular type of design but the key unique defining feature is that all of the materials are water soluble to biocompatible in products and that's kind of the key goal here so this is a movie that we created when we were still funded by DARPA in the early days it was just an example of a device that would naturally dissolve away in rain water and so this this device is this is to melt away almost immediately upon contact with water but you can choose the materials in the overall architectures to achieve operating lifetimes match to an application of interest come back to that in a little bit but I mentioned you know the bio compatibility this is how it's sort of an interesting your poor point of reference if you think about this particular circuit I just showed showed this to you it's mostly silk which is already known to be biocompatible doubtable there's no no toxicity at all and then very very thin films of the act of materials magnesium and silicon mostly but because very thin films the total mass quantity of these elements are very small 100 micrograms for magnesium 3 micrograms for silicon What does that mean in terms of your compatibility with with body processes you I told you that silicon and I'll mention it now Magnesium is also part of the recommended daily diet so if you take a look at a one a day multi-vitamin tablet and you look at the magnesium and silicon content contents through 300 milligrams magnesium 10.

[00:36:34]
Milligrams of silicon so orders of magnitude more magnesium in a vitamin pill than in this device so you think about this is a piece of trans in electronics or a really lousy vitamin tablet because you have to eat a 1000 of those in order to be relevant but we also do a lot of this knowledge a lot of animal studies to watch how these materials disappear in the body over time these are c.t. scans of a rat based model where we inserted just a basic test platform and then we can just watch it just disappear in this case over the course of the 4545 days and we can do blood chemistry analysis and other other kinds of studies we haven't seen any adverse effects of these devices so it's a last bit of my toggle and focus on clinical use cases that might be unique uniquely enabled by these kinds of devices in every example it's not something that we've thought up it's opportunities that have been brought to us by the clinical community and I'll start with one in the treatment of severe traumatic brain injuries so this is an idea that was brought to us a few years ago by neurosurgeons at Washington University's medical school and these are experts who treat severe traumatic brain injury so these are brain injuries that you know cause you to go to the hospital immediately you go into the operating room there's a surgical procedure associated with the wound and then during the recovery period it's very important to monitor continuously the intracranial pressure and temperature because both of those parameters you know very important to the recovery trajectory and if the pressure exceeds a certain value it could lead to permanent brain brain damage and the way that that monitoring is done currently is with a sensor That's why are to xterm all that acquisition electronics that goes into the intro cranial space and measures those quantities continuously but you don't need the sensor there forever you just need it during that critical recovery period once the patient has recovered beyond a certain level you don't need.

[00:38:34]
The sensors anymore and then they have to be removed surgically so the non The great of all requires a secondary surgery then for extraction because they are only needed in a temporary since they are wired in their operations so it restricts the movement of the patient which is important in the context of rehabilitation and recovery and requires next turn away interface so there's a suture site they can become a more infection so the vision that was brought to us by the neurosurgeons was essentially that if you could really make by resort will transmit devices we get rid of the wires we would eliminate the need to do the secondary surgery and we could fully suture the surgical site to eliminate eliminate some of these risks to spend a lot of time on this it's actually you know we've built out a micro.

[00:39:19]
Electro mechanical systems technology amends technology trains in but but the pressure sensing was was the most difficult and it really relies on those silicon based rain gauges I mentioned before changes in resistance with strain and you can measure that you put a strain gauge right at the edge of a drum head membrane a it's a buyer's or will polymer that's sitting over a cavity that into an underlying substrate in this case the Nano pore silicon so as the pressure of the surroundings spinal fluid changes that deflects that membrane and then you can pick up the extent of deflection electrically by measuring the resistance through that strain gauges the Serpentina structure of silicon nano membranes so that that's the way it works it scales down in dimensions very nicely you make these very very tiny they can insert into the intracranial space use modeling to connect and measure change in resistance to deflection and therefore pressure that's that's the way it works this is a time lapse image of one of those devices at different stages of dissolution you can see the silicon is partly transparent it's a indirect materials very thin so essentially transparent that's the strain gauge this is the substrate there's the drumhead membrane there's the you can see the outline there but these work pretty well so you can be.

[00:40:34]
Mark their performance against commercial i.c.p. sensors across a physiologically relevant range of pressure from about 0 to $80.00 or so millimeters of mercury and this just a time transience to show sort of equivalency between the trans in biodegradable sensor in the commercial center of course in the transients since you're measuring resistance you have to connect resistance or pressure but these are operating in a linear response regime so it's just a single calibration factor allows you to go go between the 2 so it can pick up dynamic changes in in pressure and offer stable operation up about 4 or 5 days I'll come back to that in a 2nd at that point the.

[00:41:12]
The characteristics of the pressure transistor start to drift because the device is partially dissolving away and so that becomes the essential challenge in any of these trains and like tronic devices how do you achieve very stable operation in a construct that's made out of materials that are all entirely water soluble that that's the challenge and it's kind of an interesting material science question think about these are devices that we've tested extensively in rats and so you can measure pressure transients the commercial devices the blue dots in the trans instance or here it's fully wireless we have a subdermal radio it's mostly trains in not fully trans in but mostly it is just superficial under the skin and then there's the derivable wire that connects to the pressure and temperature sensor that sits in the intracranial space kind of the way it works and so it's fully sutured up by that and you can see changes in temperature here again commercial in transit so that works pretty well the challenges they just mentioned is achieving stable operation over the full time period of interest so 4 or 5 days is that the front end you'd like to be able to run 2 weeks 3 weeks depending on the trajectory of the recovery of the individual patient and what we found is that the polymer materials are tough in the sense that they tend to swell slightly over time water permeates into them they start to slowly dissolve and it's not just from the surface.

[00:42:34]
Erosion process there's a whole reactive the fusion component as well water is coming into the materials dissolving it from the inside out in addition to from the surfaces and so in order to get a more stable device we move to a purely inorganic system where we use very thin layers of thermally grown as to is the encapsulation as I mentioned as I go to his transit but it's transit into surface erosion process that's very well controlled and can be predicted to some degree so we're still using the overall construct that I showed you before but we're getting rid of the Ga and replacing that with this very thin to silica encapsulation and so with that type of strategy you end up with stable operation over about 25 days with almost no drift you can see here so these blue dots those are commercial sensor readings in the red traces with the transition device so we're doing wireless readout we have trains in pressure and trains in temperature as well so that's 11 way to solve the materials problem is moved to an inorganic platform and away from polymers so polymers might be good it was just a really tricky set of requirements to satisfy with that type of material but any way we can do c.t. scans m.r.i. imaging and we can watch these sensors disappear over time we can also track the elemental content in various organ systems to see how these materials are alternately expelled from the body so that ultimately are filtered out in the kidneys are in and are discharged by your nation but you can see that through this timeframe of one to one to 5 weeks so my battery is dead dead here so when you go to this so you can do pressure you can also do electrical recordings as well this is an example of surface electrical measurements electric.

[00:44:26]
Up to about 30 days or so with stable operation and you can do not only single point measurements but you can come back to the site. Dia of active Alectryon x. 4 high resolution spatial and temporal mapping of electrical activity and so you can do all of that in a transition form and you can see the patterns of electrical activity in this case associated with a seizure that was pharmacologically induced in a rat based model but with a transit monitoring system and so being able to measure electrical activity again in the context of this recovery process can temper vide an important complement to just measuring the pressure and the temperature but let me take take things in a slightly different directions you can do all kinds of measurements and syncing but ultimately I think the biggest impact will be in the delivery of therapy together with sensing and maybe doing both in a closed feedback loop manner I won't force you to look at that for a long period of time.

[00:45:23]
So what turns out to be the case and again this is a use case that was brought to us by a different group of neurosurgeons again it was Washington University is that if you suffer a severe damage to a peripheral nerve you will go into an operating room the surgeons will open you up and then typically suture back the point at which you've suffered an injury it could be a transaction it could be a crush injury they do that suture process and then what they will also do in the o.r. contacts is that they will electrically stimulate the nerve as a proximal sight so upstream from the location of the engine and the biological basis for this is not fully understood but it is known that if you do electrical stimulation for about 30 minutes to an hour in the o.r. then close up the patient that their rate of recovery will exceed that of patients who have not received the electrical stimulation.

[00:46:20]
And so this is sort of a therapy that you use in the o.r. the problem with it or that it's the opportunity for trains in electronics is you would be able to do this electrical stimulation not just in the o.r. but it different time points during the recovery process because with an implantable wireless stimulator you don't need direct physical access to the to the nerves so the vision was this and it really represents kind of an engineer form of electronic medicine in the sense where you would go into the operating room maybe you do to your intro operative stimulation but then at the very tail end of the surgery you leave behind a wireless stimulator device made out of transit material so that you can suture the surgical site close and then wirelessly deliver stimulation at various dose profiles throughout the healing process to further yield further benefits in accelerated newer generation beyond what's possible just with electrical stimulation confined to the intra operative period so that was the that was the vision and from an engineering standpoint you know at that point at that stage we had all the you know capabilities to to build the build the hardware so this is a fully transition wirelessly powered and wirelessly controlled nerve stimulator so it consists of a coffee a wireless harvesting unit so there's an r.f. diode to do the rectification and then all of the other materials as well are.

[00:47:46]
Resort bubble so these are some of the electromagnetic characteristics of the devices I won't say too much about that if you're interested and happy to have a conversation afterwards but this is what the device looked like so the very thin they're flexible they offer you a noninvasive cuff interface to the nerve and then this power harvesting and control unit back at the back the other side of the of the system so this is the result of a tremendous number of rat studies where we've artificially collaborators of artificially damaged Sadek nerve in this.

[00:48:20]
Either transaction or cough and then leave they leave these wireless stimulators behind and then you measure the extent of healing by quantifying e.g. amplitude associate with muscle activity stimulated electrically as a function of time in weeks for 3 different cases you can imagine there's a there are enormous phase space here due to explore in terms of stimulation waveform stimulation voltages currents durations and so on but this is just an example of what you could do one day electrical stimulation that just corresponds to the intra operative procedure that it's used currently and you can see the recovery trajectory illustrated there with the black symbols and then extend it out to electrical stimulation one sad day for 3 days and then once a day for 6 days you need again uniquely enabled by by the transition implant and you can see that the additional stimulation not only accelerates the rate of recovery the slope but it improves the point of the recovery as well because that terminal point you know increases in terms of.

[00:49:31]
Amplitude as you extend out the the stimulation. This is what it looks like you know at a couple different stages during the healing process your weeks 8 and 21 weeks the device is completely gone and there's no evidence of any residue left over either at the at the point of the nerve interface the cough or the back and Harvester either so that's kind of one example you might say Ok well you can do purple nerves but then like what else it turns out you know there are a lot of application opportunities enabled by a trans in electrical stimulator and this just highlights a number of different areas that we're And that we're working on I'll highlight a couple of different examples This Is Spinal Cord muscle stimulator it's easy to do the engineering and adapt the devices to different interface points across the body this is a an example of an application that was brought to us by a cardiologist to Northwestern and evidently there are opportunities for transients pacemaking following an open heart surgical process so you know you have a patient at risk they have to have an open heart surgery and typically they will leave in a pacing lead that can be activated during the recovery process to the extent that that might be necessary depending on the patient's condition and author highlight the problems with that kind of you know traditional temporary pacemaker but they came to us and ask us if we could build a trans in pacemaker for that kind of post surgical recovery application and turns out to be really really easy to do that the problem with the non trans in pacemaker is you can get the lead in there's no problem with doing that but over the course of several weeks it becomes enveloped in scar tissue essentially in up with this 5 brought it shell around the pacing lead so that extraction becomes difficult without you know damn inducing additional damage to the to the epic.

[00:51:35]
Surface or depending on where that where the lead is located and so that's it's a big practical problem I am told by by our collaborators that would go away you know if you if you were able to transition to a fully transient wireless based device and so we've been able to put that together so it's the same type of concepts in wireless control and power transfer just you know the form factor is a little bit different and you know we've been able to do stimulation of variety of different animal models starting with the with the rat So here we have a rat in a cage there's an intent of surrounding the outside of the cage and we can power that with r.f. and do pacing at any kind of stimulation protocol you might might imagine and these are e.c.g. recordings with and without pacing just to show the the functionality but we've done not only rats but rabbits and and humans as well but not actual humans actually explanted cardiac tissue from organ donors but we can do that and and it works even at that even at that scale so I think it's an important area where where these ideas of materials science might offer the potential for impact to talk to pacemakers intercranial my monitor's nerve stimulators working on bone stimulators of different things you can do an anti-bacterial around thermal therapy and we have programmable drug release vehicles as well in all cases where you know this transient materials construction offers a key a key feature in the way that the devices operate so with that I think I'm out of time I'm just going to conclude by acknowledging the senior class of raters who are very collaborative in everything we do working with folks in engineering sciences that clinical medical interface that that's very important to us as well and some of the folks that we're working with are listed on this slide so those folks are important everything that we do but it's the students in the post docs who actually do everything so I always like to conclude by.

[00:53:35]
Acknowledging their their efforts I just get to talk about this stuff they they do all the work so it's up amazing collection of postdocs and grad students undergrad lots of undergrads all the kids with their hands raised or undergrad sewed typically 30 or 40 in the group at any given time really great great group of people and fun fun to work with so so with that I'll just conclude I'll be happy to answer questions if you have any.

[00:54:02]
One. 0 yeah. He. Said. About me that use. Yeah so it's kind of a I so the manufacturing approaches are kind of a blend of what's done in the semiconductor industry today. And some innovative approaches that you have to bring to bear on these materials because of their water solubility So a lot of the process steps that Intel would use to make an i.c. chip are in are not applicable to these classes of materials because they're dissolved away you know during during the process so so we like I mentioned this kind of transfer process there are several stages at which you know the kind of a dry physical assembly approach like that is kind of key in terms of how we put these things together but in other cases we're using similar types of evaporation tools to deposit the metals were using pretty well established techniques to the silicon to control the Dopping levels and the patterns of dope and in many cases those steps can be done you know before transfer to the transience substrate so you eliminate some of the temperature constraints associated with the transit materials and the inability to use processing with those materials so.

[00:55:45]
Yeah. We think so so we've spent a lot of time asking a question what would I need to modify from a foundry based fab facility to allow the production of trans in electronics so if you think about silicon fab let's say an s.o.i. based fab so silicon enslaves the large very thin silicon on an insulating layer of 2 supported by a silicon wafer like how what would I need to do to modify a fad that processes those kinds of wafers to yield a purely transience device and so we work with Lincoln Lab They have a 90 nanometer facility were funded by DARPA a few years ago to to prove out material substitution to get rid of.

[00:56:30]
You replace it with tungsten they're already using tungsten plugs the so we're going to solve his transiency as I go to his trans and they are already using silicon I tried for different dielectric layers we've shown that that's trans in so then if you replace if you do the aluminum or copper replacement with tungsten then essentially you just need to get rid of the underlying handle wafer and the end up with a very thin integrated circuit where all the different components are water soluble so that gets you to the i.c. component then you have to have a transients equivalent of a printed circuit board platform so you can take those i.c. components and assemble them together with passives with the right routing.

[00:57:10]
Traces to build build a system that's where these kind of conductive pastes come in because we can do in 10 is that traces interconnects and so on and so so that's the way we kind of piece it together was try to take what is done today and modify it rather than chart or try to reinvent everything and I think that kind of transfer process is pretty key you know in terms of moving these foundry produced trans integrated circuits onto a p.c.b. platform that's made out of transit materials so it's not a super Chris answer to your question because it really depends on all of the details but that's kind of the flavor of it.

[00:58:02]
Wow. Yeah I think it's a great great great question so we've been having those discussions with our clinical collaborators right now the question is like how do you stage out you know technologies that allow you to generate you know a revenue stream in the relatively near term while you build out you know additional application areas like how do you do that and how you think about the regulatory process because I don't think the f.d.a. has ever had to deal with transients like biodegradable electronics so that's a whole kind of unknown I guess in terms of how you move there's one argument that would say it's going to be easier to get f.d.a. approval for these type of implants compared to a pacemaker because the devices are only there for a finite amount of time and they're eventually disappearing by you know hydrolysis or in semantic degradation but then the flip side of that is they've never looked at this before and then the other problem is these systems don't typically dissolve in a completely deterministic way where things just get thinner and thinner and thinner and disappear Typically they will fragment at some point and they're fracture into small pieces and then where do those pieces go because if those pieces ever enter the bloodstream it could be a big problem because it could represent blockage of blood flow even if that strands in if it's even for a few minutes could be big problem cause a stroke or somebody's got so we've tried to stay outside of any blood flow path we haven't done anything in the interim.

[00:59:32]
In Toronto cardio space. Space or anything in the blood vessels so so it's a direction that we want to go I mean that's kind of the whole purpose of what we're doing is to build devices that can actually be used with humans but it's it's non-trivial So we're thinking it through and trying to identify opportunities that are large enough markets that would allow you to get get a business started but at the same time near term enough that you can that you could get there right in a few few years so so I think it's.

[01:00:04]
It's still a topic of discussion we put together a company a few years ago but then decide it was little bit too early so we'd like to have things a little bit more solidified to be able to sort of push the technology along in the academic lab but I would say over the next 23 years I hope that we can get to a position that we can start moving things into a commercial space so I think it's a great question something we're thinking about a lot.

[01:00:30]
Yeah. Yeah that's a great question so if you think about immune response and rejection and inflammation is driven by the type to consider 2 main considerations one would be just chemistry of the materials themselves and the products of their dissolution so it's sort of a chemistry question the other one is you know even if you have a material that's biocompatible you know the chemistry level if it's mechanically interface to the body in a way that creates mechanical stresses in your irritation that can be a separate problem right so the 2nd one I guess both of them to some extent are highly dependent on the use case the nature of the device the place in the body where the devices are located but I would say I wouldn't say that there's no chance of problem in any kind of scenario but I can say that we have never observed an issue with with information we have done you know detailed studies of immune response both at the level of cell based assayers and small animals primarily.

[01:01:39]
Intercranial cardiac surface nerve interface just general subdermal we've we've looked at all of those locations but you know the chemistry is different at different places in the body you could there could be some unexpected effects due to position or due to the details of how the devices have been built but for the for the application that I described we've looked at those kinds of questions very carefully and haven't haven't seen anything that problematic but I think it needs to be case by case basis because a lot of the biological responses are not well understood so you can't really predict that you have to go into the animals and see see what happens yeah yeah.

[01:02:26]
Wife. Yeah that's a great question I think as you highlighted most of the applications we're talking about you have open access to the body as a natural consequence of a surgical procedure that needs to happen anyway to not opening up a patient strictly for the purpose of inserting one of these trans in devices patients already open right and you're just leaving a device behind just before they're closed up so the question that you're asking is would it be possible to deploy these devices in use case scenarios that don't involve a natural access point right as part of the standard of care and I don't know the answer to that question we thought about it like if you could create some kind of you know device that could be deployable So it could be folded up into a tiny you know geometry and maybe injected with a syringe and then once it's in the body it don't unfurls in some way so I think there's some really cool concepts that probably need to be.

[01:03:28]
Thought about in the context of materials and mechanical actuation strategies and so on so we've thought about it I think especially in the context of brain interface if you could just do a very tiny hole and then you inserted of a device in that way but again for these severe traumatic brain injuries this is not just getting knocked on the head of the football field this is something like car crash or something like that your head is split open at some level anyway and so you're you're you're opening up that that intracranial space or even the procedures used to treat epilepsy the whole cap of the skull is removed so the brain is exposed and get devices on there but I think like highly like minimally invasive approaches to deployment that that's a great area think about and we don't have the answers but we kind of kind of thought about it but if you have a great idea that's that's a good space to you know think about research opportunities.

[01:04:36]
And thank you.