Bioelectronics is a multidisciplinary field that combines biology and electronics to develop devices that interface with biological systems. It plays a crucial role in the healthcare industry as it enables innovations like advanced prosthetics, electronic skins (e-skins), and exoskeletons to improve the quality of life for individuals by restoring or enhancing bodily functions. This integration of biological systems with electronic devices is transforming healthcare by allowing for more personalized, efficient, and responsive treatments.<h2 dir="ltr">The Evolution of Bioelectronics</h2><h3 dir="ltr">From Concept to Application</h3>Bioelectronics emerged in the late 18th century with Luigi Galvani's experiments, which discovered that electricity could stimulate muscles, introducing the concept of "animal electricity." His work laid the foundation for understanding neuroelectricity. In the 1930s, electrical stimulation research led to the development of cochlear implants. The field gained momentum in the 1940s and 1950s when Alan Hodgkin and Andrew Huxley recorded action potentials in nerve cells, earning them a Nobel Prize in 1963.&nbsp;1Currently, bioelectronics in medicine is considered to be a rapidly growing market.&nbsp;1&nbsp;Bioelectronics is currently being applied in various areas of healthcare, including wearable devices, implantable sensors, neural interfaces, and drug delivery systems. For instance, wearable electronics like health monitors and smart textiles are used to track vital signs in real time. Similarly, implantable devices, such as neural interfaces, facilitate direct communication between the brain and external devices.<h2 dir="ltr">Key Technologies in Bioelectronics</h2>The current state of bioelectronics became possible due to several advanced key technologies. For instance, flexible electronics technologies allow devices to conform to the body's contours to enhance user comfort and enable continuous monitoring. Sensors embedded within these systems can capture and relay physiological data. Similarly, biocompatible materials, like bioceramics, are compatible with the body and minimize adverse reactions.Another important technology in this regard is additive manufacturing, specifically DIW, since it allows users to print electronic structures with biocompatible inks layer by layer with high precision, which helps develop complex biomedical devices tailored to individual patients.<h1 dir="ltr">Understanding Biocompatible Inks and Their Role in Bioelectronics</h1><h3 dir="ltr">What Are Biocompatible Inks?</h3>Biocompatible inks are specialized materials designed for safe interaction with biological systems which makes them significant in developing bioelectronics. These inks are typically composed of polymers, hydrogels, conductive materials like gold and silver-silver chloride, or other bio-friendly substances that can mimic the properties of living tissues, such as flexibility and conductivity. The primary role of biocompatible inks in bioelectronics is to create interfaces that can integrate smoothly with biological tissues, enabling innovations like flexible sensors, and implantable devices.<h3 dir="ltr">Biocompatible Inks in DIW Systems</h3>DIW technology is an advanced additive manufacturing method used to print electrical circuits, features, patterns, and traces by extruding ink from a fine nozzle in a precise and controlled manner. DIW can print biocompatible inks onto biocompatible substrates for in- or on-body monitoring and recording of bioelectric signals.&nbsp;Moreover, DIW offers high precision and flexibility, making it ideal for creating customized biomedical solutions as it allows the users to tune various parameters, including extrusion pressure, nozzle speed, and material calibration, to tailor the printed material's properties to the specific needs of a patient.<h3 dir="ltr">Compatibility with Common Substrates</h3>DIW systems are highly versatile and allow precise dispensing of various materials with differing mechanical and electrochemical properties. This adaptability makes DIW well-suited for printing onto organic polymer substrates like PEDOT:PSS, which is a combination of two distinct polymers (poly(3,4-ethylenedioxythiophene) and polystyrene sulfonate).&nbsp;PEDOT:PSS offers excellent electrical conductivity, flexibility, and biocompatibility, making it an ideal substrate for biosensing applications. This compatibility of PEDOT:PSS with DIW helps create complex, multifunctional devices where the electrochemical behavior of this substrate enhances the functionality of printed sensors, leading to innovative biomedical solutions.<h1 dir="ltr">On-Body and In-Body Bioelectronics: Current Applications and Future Prospects</h1><img src="https://images.wevolver.com/eyJidWNrZXQiOiJ3ZXZvbHZlci1wcm9qZWN0LWltYWdlcyIsImtleSI6ImZyb2FsYS8xNzMwOTg0OTIxMDA0LUdvbGQgZWxlY3Ryb2RlIG9uIHNraW5fMS5qcGciLCJlZGl0cyI6eyJyZXNpemUiOnsid2lkdGgiOjk1MCwiZml0IjoiY292ZXIifX19" style="width: 100%px;" class="fr-fic fr-dib">Over the next decade, the bioelectronic technologies market is expected to witness significant growth, projected to expand from $23.9 billion in 2024 to approximately $33.6 billion by 2029, achieving a compound annual growth rate (CAGR) of 7.0%. This growth is expected due to the rising elderly population and increasing prevalence of cardiovascular and neurological disorders. Non-invasive electroceutical devices, such as on-body bioelectronics like transcutaneous electrical nerve stimulation (TENS) devices, and in-body bioelectronics like implantable neurostimulators, are anticipated to grow at the highest rate, driven by advancements in technology and increased research and development investments. 2<h2 dir="ltr">On-Body Bioelectronics</h2>On-body bioelectronics refers to electronic devices and systems that are designed to be worn directly on the skin or embedded into wearable materials to monitor, stimulate, or interact with biological processes in the human body. Wearable devices like smartwatches and fitness trackers that monitor heart rate, body temperature, and other vital signs in real time are among the most common applications of on-body bioelectronics. Similarly, smart textiles are another type of on-body bioelectronics that include fabrics integrated with electronic components that can measure biomechanical movements, making them advantageous in sports, rehabilitation, and clinical monitoring.<h2 dir="ltr">In-Body Bioelectronics</h2>In-body bioelectronics, like pacemakers, cochlear implants, and neural interfaces, are implanted or inserted within the human body to monitor physiological processes, deliver therapies, or interact with biological tissues at a deeper level. For instance, neural interfaces enable direct communication between the brain and external devices, providing a unique approach to treating conditions like Parkinson's disease and epilepsy.&nbsp;<h2 dir="ltr">Multifunctional Bioelectronics</h2>Multifunctional bioelectronics aims to combine several functions, such as drug delivery, diagnostics, and therapeutic interventions, into a single device, enhancing their biomedical applications. For instance, silk-based transient bioelectronics, powered by triboelectric nanogenerators (TENGs) enable real-time in vivo monitoring and therapeutic treatments. These systems are self-powered and biodegradable, with adjustable lifespans and sensitivity through silk molecular customization.&nbsp;3&nbsp;These multifunctional devices have the potential to revolutionize personalized medicine by providing more comprehensive health solutions.<h2 dir="ltr">Challenges&nbsp;</h2>Integrating bioelectronics into healthcare presents significant inherent regulatory and ethical challenges. As bioelectronic devices are advancing, especially those used in the medical industry like pacemakers and neural implants, the impact on users' health means that regulatory and ethical considerations are increasing in importance.Ensuring the safety and efficacy of these devices requires rigorous testing and compliance with regulatory standards. Ethical considerations also arise regarding user privacy, data security, and informed consent, especially when sensitive health information is collected and shared. Addressing these challenges is crucial to building public trust and ensuring the responsible use of bioelectronics.Moreover, although on-body bioelectronics are beneficial, there are also challenges in developing on-body bioelectronics, particularly regarding power supply, and user comfort. These challenges require innovative solutions, and some solutions, like <a href="https://www.voltera.io/application-whitepapers/printing-magnesium-zinc-battery-saral-inks-pet?utm_campaign=Wevolver&utm_source=wevolver&utm_term=intersection-biology-technology-future-bioelectronics&utm_content=mg-zn-battery-white-paper">flexible batteries</a>, have already made significant differences in tackling some of these challenges.Biocompatibility is another key challenge in developing in-body bioelectronics as these devices are placed inside the body; they must be made from compatible materials that do not provoke immune responses and can operate without causing harm to surrounding tissues. Moreover, maintaining the device's functionality over time, despite the harsh environment within the body, which includes exposure to fluids, enzymes, and mechanical stresses, is also a significant challenge.<h2 dir="ltr">Opportunities and Emerging Trends: The Future of Bioelectronics</h2>Currently, one of the most compelling emerging trends in bioelectronics is the development of smart bioinks. These bioinks have enhanced functionalities, such as responding to environmental changes like temperature, pH, and chemical stimuli. For instance, smart bioinks can be designed to release therapeutic agents in response to specific stimuli, promoting targeted healing and enhancing treatment efficacy.&nbsp;4&nbsp;This adaptability of smart bioinks can lead to future bioelectronic devices that dynamically adjust to the body's needs, further improving their therapeutic potential.<h1 dir="ltr">Voltera's Role in Advancing Bioelectronics and Biocompatible Inks</h1><iframe src="https://www.youtube.com/embed/zsniZR1if1s?&amp;wmode=opaque&amp;enablejsapi=1&amp;origin=https://www.wevolver.com" frameborder="0" allowfullscreen="" class="fr-draggable" data-lf-form-tracking-inspected-kn9eq4roawkarlvp="true" data-lf-yt-playback-inspected-kn9eq4roawkarlvp="true" data-lf-vimeo-playback-inspected-kn9eq4roawkarlvp="true" style="width: 640px; height: 460px;" data-gtm-yt-inspected-24="true" id="654705223" title="Printing ECG Electrodes with Gold Ink on Voltera NOVA">&nbsp;&nbsp;&nbsp;</iframe><a href="https://www.wevolver.com/profile/voltera">Voltera</a> is a leading provider of advanced materials dispensing solutions for printing bioelectronics prototypes. Voltera's <a href="https://www.voltera.io/nova?utm_campaign=Wevolver&utm_source=wevolver&utm_term=intersection-biology-technology-future-bioelectronics&utm_content=nova-lp">NOVA</a> supports a wide range of materials, allowing researchers to test and experiment with various substrates and conductive inks. This flexibility allows innovation in bioelectronics, offering opportunities for breakthroughs in multifunctional bioelectronics devices. For instance, NOVA enables researchers to print biocompatible inks, such as gold and silver-silver chloride with exceptional precision to facilitate prototyping complex bioelectronics. This advanced system supports the development of traditional rigid electronics, as well as flexible hybrid electronics (flexible, stretchable, and conformable).&nbsp;In particular, with a minimum line width of 100 µm and temperature-controlled dispensing, NOVA enables users to dispense biocompatible inks, pastes, gels, and adhesives on stretchable, soft, and flexible substrates, unlocking the ability to print bioelectronics that conform to the body’s natural contours.<h2 dir="ltr">Supporting Research and Innovation</h2>Researchers worldwide are using Voltera's tools to push the boundaries of bioelectronics. For example, in a 2024 <a href="https://iopscience.iop.org/article/10.1088/2634-4386/ad63c6/meta">study</a>, researchers utilized the Voltera’s NOVA PCB printer to fabricate organic electrochemical transistors (OECTs) as part of their investigation into electrochemical organic neuromorphic devices (ENODes). NOVA was employed to directly print transistors with specific PEDOT formulations onto glass substrates, enabling the precise patterning of silver feedlines and contact pads. The team achieved a compact design with a high degree of control over the devices' channel and gate structures, facilitating the integration of biocompatible gel-electrolytes. This method allowed the study to examine ENODe performance under varied electrolyte conditions, specifically focusing on short- and long-term plasticity for potential applications in brain-chip interfacing.5Similarly, in another 2022 <a href="https://doi.org/10.1109/FLEPS53764.2022.9781535">study</a>, researchers utilized Voltera's NOVA to fabricate silver-based tattoo electrodes to monitor bioelectric signals. NOVA enabled precise extrusion printing of high-viscosity silver flake ink on porous tattoo paper, leading to electrodes with lower sheet resistance and better electrical performance compared to inkjet-printed alternatives. This improved efficiency by minimizing ink absorption into the substrate, and reducing impedance in bioelectrical measurements.&nbsp;6These researches, along with many others, are a testament to Voltera's commitment to supporting the next generation of bioelectronic innovations. Voltera's products, like NOVA and V-One, ensure that the next generation of devices continues to improve the quality of life for patients worldwide.<h1 dir="ltr">Conclusion</h1>The importance of bioelectronics is self-evident, as these technologies have immense significance in advancing modern personalized medicine, real-time health monitoring, and patient outcomes, which ultimately have the potential to revolutionize the future of medicine. DIW technology is integral to these advancement as it enables precise prototyping of bioelectronic devices with biocompatible inks in both on-body and in-body applications.&nbsp;The projected market growth of bioelectronics is up to $33.6 billion by 2029, which indicates that this field is rapidly advancing and holds immense potential to reshape the future of healthcare.<h2 dir="ltr">Explore the future of bioelectronics applications&nbsp;</h2>For researchers and engineers looking to explore the next frontier of bioelectronics, Voltera's platforms provide the tools and support necessary to advance the field. <a href="https://www.voltera.io/book-a-meeting?utm_campaign=Wevolver&utm_source=wevolver&utm_term=intersection-biology-technology-future-bioelectronics&utm_content=book-a-meeting">Book a call with Voltera</a> to learn how their technology can contribute to <a href="https://www.voltera.io/applications/bioelectronics?utm_campaign=Wevolver&utm_source=wevolver&utm_term=intersection-biology-technology-future-bioelectronics&utm_content=bioelectronics-application-page">your bioelectronics applications</a>.<h1 dir="ltr">References</h1><ol><li dir="ltr">Stavrinidou, E., &amp; Proctor, C. M. (Eds.). (2022). Introduction to Bioelectronics: Materials, Devices, and Applications. AIP Publishing LLC. <a href="https://doi.org/10.1063/9780735424470_001">https://doi.org/10.1063/9780735424470_001</a></li><li dir="ltr">Electroceuticals/Bioelectric Medicine Market worth $33.6 billion by 2029. [Online] Markets and Markets. Available at: <a href="https://www.marketsandmarkets.com/PressReleases/electroceutical.asp">https://www.marketsandmarkets.com/PressReleases/electroceutical.asp</a> (Accessed on September 4, 2024)</li><li dir="ltr">Zhang, Y., Zhou, Z., Fan, Z., Zhang, S., Zheng, F., Liu, K., ... &amp; Tao, T. H. (2018). Self‐powered multifunctional transient bioelectronics. Small. <a href="https://doi.org/10.1002/smll.201802050">https://doi.org/10.1002/smll.201802050</a></li><li dir="ltr">Maan, Z., Masri, N. Z., &amp; Willerth, S. M. (2022). Smart bioinks for the printing of human tissue models. Biomolecules. <a href="https://doi.org/10.3390/biom12010141">https://doi.org/10.3390/biom12010141</a></li><li dir="ltr">Rana, D., Kim, C. H., Wang, M., Cicoira, F., &amp; Santoro, F. (2024). Tissue-like interfacing of planar electrochemical organic neuromorphic devices. Neuromorphic Computing and Engineering. <a href="https://iopscience.iop.org/article/10.1088/2634-4386/ad63c6/meta">https://iopscience.iop.org/article/10.1088/2634-4386/ad63c6/meta</a></li><li dir="ltr">El-Hajj, Y., Ghalamboran, M., &amp; Grau, G. (2022, July). Inkjet and extrusion printed silver biomedical tattoo electrodes. In 2022 IEEE International Conference on Flexible and Printable Sensors and Systems (FLEPS) IEEE. <a href="https://doi.org/10.1109/FLEPS53764.2022.9781535">https://doi.org/10.1109/FLEPS53764.2022.9781535</a></li><li dir="ltr">Voltera [Online] Wevolver, Available at: <a href="https://www.wevolver.com/profile/voltera">https://www.wevolver.com/profile/voltera</a> (Accessed on September 4, 2024)</li><li dir="ltr">NOVA. The future of printed electronics [Online] Voltera, Available at: <a href="https://www.voltera.io/nova">https://www.voltera.io/nova</a> (Accessed on September 4, 2024)</li><li dir="ltr">V-One. PCB prototyping made easy [Online] Voltera, Available at: <a href="https://www.voltera.io/v-one">https://www.voltera.io/v-one</a> (Accessed on September 4, 2024)</li></ol>

This article explores the role of biocompatible inks in bioelectronics, particularly within Direct Ink Writing (DIW) systems and forecasts future trends and challenges in on-body and in-body bioelectronic technologies over the next decade.

The Intersection of Biology and Technology: Exploring the Future of Bioelectronics

<h2 id="isPasted">Introduction</h2>Polyether Ether Ketone (PEEK) is a high-performance engineering thermoplastic renowned for its outstanding mechanical properties, chemical resistance, and thermal stability. It finds utility in stringent sectors such as aerospace, medical, and electronics due to its robustness. While injection molding stands out as the most effective manufacturing method for crafting precise PEEK components, mastering this technique requires a deep understanding of both the material and the process, especially when using compact injection molding systems. <h3>1. Material Properties of PEEK</h3>PEEK is favored for high-performance applications owing to its distinctive characteristics:High Temperature Resistance: PEEK endures continuous exposure to temperatures as high as 250°C, making it suitable for components that experience high thermal loads.Chemical Resistance: Its resistance to a wide array of chemicals ensures durability in aggressive environments.Mechanical Strength and Toughness:&nbsp;PEEK offers superior strength and stiffness along with excellent wear resistance, which is crucial for parts subjected to high mechanical loads.Biocompatibility: Its compatibility with bodily tissues makes it ideal for medical implant applications.<h3>2. Challenges in Injection Molding PEEK</h3>Any injection molding machine, designed for precision and small-scale production, must be carefully calibrated for PEEK due to its high melting point (343°C) and unique processing requirements:Processing Temperatures: Optimal mold temperatures range between 160°C and 200°C, which helps achieve desired crystallinity. The injection temperatures should be maintained between 370°C and 400°C to facilitate smooth flow.Cycle Time: PEEK's inherent properties necessitate longer cooling times compared to more conventional thermoplastics, potentially impacting production efficiency.Mold Design: Given PEEK's minimal shrinkage, the mold must be designed with high precision to ensure accurate dimensional outcomes.<h3>3. Critical Mold Design Considerations</h3>Effective mold design is vital:Gate Design: Small, uniformly-sized gates such as pin or edge gates are recommended to minimize residual stresses.Ventilation: Proper venting is crucial to prevent gas entrapment and eliminate burn marks.Mold Surface Finish: A highly polished mold surface enhances flow, reducing friction and improving the quality of the finished parts.<h3>4. Injection Molding Parameters</h3>Tailoring the injection machine settings is crucial for optimal results:Injection Pressure: High pressures are necessary to adequately fill the mold.Injection Speed: A slow to moderate injection speed helps prevent shear heating and material degradation.Cooling and Crystallization: Effective cooling management is essential to control crystallization and prevent warping or deformation.<h3>5. Post-Molding Processes</h3>To further enhance the properties of PEEK parts, certain post-processing treatments may be required:Annealing: This heat treatment relieves internal stresses and enhances dimensional stability.Surface Treatments: Techniques such as polishing or coating can significantly improve the surface quality of the components.<h3>6. Common Defects and Troubleshooting</h3>Understanding common defects can aid in troubleshooting:Warping and Shrinkage: Maintain proper cooling rates and ensure uniform mold temperature control.Bubbles and Voids: Fine-tune injection pressure and verify material drying processes prior to molding.Burn Marks: Ensure sufficient venting and consider reducing the injection speed if necessary.<h3>Conclusion</h3>Mastering PEEK injection molding demands precise control over material properties, mold design, and processing parameters. By meticulously attending to these critical aspects, manufacturers can consistently produce high-quality, reliable PEEK components for advanced applications.#peekparts #injectionmolding #apsxllc #peek #medicalparts #biomedical

While injection molding stands out as the most effective manufacturing method for crafting precise PEEK components, mastering this technique requires a deep understanding of both the material and the process, especially when using compact injection molding machines.

Critical Aspects of PEEK Injection Molding Process

MIT researchers have developed a miniature, chip-based “tractor beam,” like the one that captures the Millennium Falcon&nbsp;in the film “Star Wars,” that could someday help biologists and clinicians study DNA, classify cells, and investigate the mechanisms of disease.Small enough to fit in the palm of your hand, the device uses a beam of light emitted by a silicon-photonics chip to manipulate particles millimeters away from the chip surface. The light can penetrate the glass cover slips that protect samples used in biological experiments, enabling cells to remain in a sterile environment.Traditional optical tweezers, which trap and manipulate particles using light, usually require bulky microscope setups, but chip-based optical tweezers could offer a more compact, mass manufacturable, broadly accessible, and high-throughput solution for optical manipulation in biological experiments.However, other similar integrated optical tweezers can only capture and manipulate cells that are very close to or directly on the chip surface. This contaminates the chip and can stress the cells, limiting compatibility with standard biological experiments.Using a system called an integrated optical phased array, the MIT researchers have developed a new modality for integrated optical tweezers that enables trapping and tweezing of cells more than a hundred times further away from the chip surface.“This work opens up new possibilities for chip-based optical tweezers by enabling trapping and tweezing of cells at much larger distances than previously demonstrated. It’s exciting to think about the different applications that could be enabled by this technology,” says Jelena Notaros, the Robert J. Shillman Career Development Professor in Electrical Engineering and Computer Science (EECS), and a member of the Research Laboratory of Electronics.Joining Notaros on the paper are lead author and EECS graduate student Tal Sneh; Sabrina Corsetti, an EECS graduate student; Milica Notaros PhD ’23; Kruthika Kikkeri PhD ’24; and Joel Voldman, the William R. Brody Professor of EECS. The research&nbsp;<a href="https://www.nature.com/articles/s41467-024-52273-x" target="_blank">appears today in&nbsp;Nature Communications</a>.<h2>A new trapping modality</h2>Optical traps and tweezers use a focused beam of light to capture and manipulate tiny particles. The forces exerted by the beam will pull microparticles toward the intensely focused light in the center, capturing them. By steering the beam of light, researchers can pull the microparticles along with it, enabling them to manipulate tiny objects using noncontact forces.However, optical tweezers traditionally require a large microscope setup in a lab, as well as multiple devices to form and control light, which limits where and how they can be utilized.“With silicon photonics, we can take this large, typically lab-scale system and integrate it onto a chip. This presents a great solution for biologists, since it provides them with optical trapping and tweezing functionality without the overhead of a complicated bulk-optical setup,” Notaros says.But so far, chip-based optical tweezers have only been capable of emitting light very close to the chip surface, so these prior devices could only capture particles a few microns off the chip surface. Biological specimens are typically held in sterile environments using glass cover slips that are about 150 microns thick, so the only way to manipulate them with such a chip is to take the cells out and place them on its surface.However, that leads to chip contamination. Every time a new experiment is done, the chip has to be thrown away and the cells need to be put onto a new chip.To overcome these challenges, the MIT researchers developed a silicon photonics chip that emits a beam of light that focuses about 5 millimeters above its surface. This way, they can capture and manipulate biological particles that remain inside a sterile cover slip, protecting both the chip and particles from contamination.<h2>Manipulating light</h2>The researchers accomplish this using a system called an integrated optical phased array. This technology involves a series of microscale antennas fabricated on a chip using semiconductor manufacturing processes. By electronically controlling the optical signal emitted by each antenna, researchers can shape and steer the beam of light emitted by the chip.Motivated by long-range applications like lidar, most prior integrated optical phased arrays weren’t designed to generate the tightly focused beams needed for optical tweezing. The MIT team discovered that, by creating specific phase patterns for each antenna, they could form an intensely focused beam of light, which can be used for optical trapping and tweezing millimeters from the chip’s surface.“No one had created silicon-photonics-based optical tweezers capable of trapping microparticles over a millimeter-scale distance before. This is an improvement of several orders of magnitude higher compared to prior demonstrations,” says Notaros.By varying the wavelength of the optical signal that powers the chip, the researchers could steer the focused beam over a range larger than a millimeter and with microscale accuracy.To test their device, the researchers started by trying to capture and manipulate tiny polystyrene spheres. Once they succeeded, they moved on to trapping and tweezing cancer cells provided by the Voldman group.“There were many unique challenges that came up in the process of applying silicon photonics to biophysics,” Sneh adds.The researchers had to determine how to track the motion of sample particles in a semiautomated fashion, ascertain the proper trap strength to hold the particles in place, and effectively postprocess data, for instance.In the end, they were able to show the first cell experiments with single-beam optical tweezers.Building off these results, the team hopes to refine the system to enable an adjustable focal height for the beam of light. They also want to apply the device to different biological systems and use multiple trap sites at the same time to manipulate biological particles in more complex ways.“This is a very creative and important paper in many ways,” says Ben Miller, Dean’s Professor of Dermatology and professor of biochemistry and biophysics at the University of Rochester, who was not involved with this work. “For one, given that silicon photonic chips can be made at low cost, it potentially democratizes optical tweezing experiments. That may sound like something that only would be of interest to a few scientists, but in reality having these systems widely available will allow us to study fundamental problems in single-cell biophysics in ways previously only available to a few labs given the high cost and complexity of the instrumentation. I can also imagine many applications where one of these devices (or possibly an array of them) could be used to improve the sensitivity of disease diagnostic.”

This chip-based "tractor-beam," which uses an intensely focused beam of light to capture and manipulate biological particles without damaging the cells, could help biologists study the mechanisms of diseases. Credit: Sampson Wilcox, RLE

The tiny device uses a tightly focused beam of light to capture and manipulate cells.

MIT engineers create a chip-based tractor beam for biological particles

Sometimes a researcher goes into the lab and comes out with a discovery. Sometimes that discovery is issued a patent. Very rarely does the process also involve an undergraduate, a potential breakthrough for biomedical printing and cell therapy, and a little help from Bill Nye ’77 the Science Guy.As an ambitious sophomore, Jared Matthews ’21 was looking for a research project and he approached <a href="https://www.bme.cornell.edu/faculty-directory/lawrence-bonassar" target="_blank">Lawrence Bonassar</a>, the Daljit S. and Elaine Sarkaria Professor in Biomedical Engineering and in Mechanical and Aerospace Engineering in Cornell Engineering. Together they created a smart sensor that attaches to the tip of a syringe to measure, in real time, the concentration and viability of the cells that pass through it – a device that would enable surgeons and biomanufacturers to produce higher quality implants of living tissue, even organs.“A lot of inventions come out of this university,” Bonassar said. “Not a lot of them involve undergraduates, and not a lot of them happened during COVID. Most of our peers didn’t even have undergraduates on campus in fall 2020. And here we have an undergraduate not only on campus, but working in a lab and inventing and patenting something that could be really impactful.”For two decades, Bonassar’s lab has been making bioprinting technology that combines cells with materials such as hydrogel ink to fabricate new <a href="https://news.cornell.edu/stories/2022/06/cornellian-founded-company-implants-3d-bioprinted-ear" target="_blank">living tissues and organs</a> that function better than inanimate implants. But in bringing this technology from the lab to the clinic, one persistent problem has remained.“One of the real challenges in manufacturing is the quality control,” Bonassar said. “If you’re going to print something that’s alive with cells in it, the first thing you need to know is how many cells are in it? And what fraction of them are alive?”Previous attempts to make those types of measurements with bioprinting have relied upon optical detectors, which measure the light reflected off cells as they are squeezed through a channel. However, such approaches require the concentration of cells to be low, greatly limiting the range of applications to which this idea is applicable and stymieing attempts to construct anything with a high cell density, such as organs. And it couldn’t be done in real time.‘A crazy idea’When Matthews arrived at Cornell as a freshman, he already had a field of interest – biomedical engineering – and a head start on research. During his senior year of high school in central Massachusetts, he’d worked for Washington University professor Farshid Guilak, analyzing computed tomography images of biological samples and building specialized lab apparatuses that combined CAD software and 3D printing.Upon being accepted to Cornell, Matthews visited campus in April 2017, and he made a bold move. He stopped by the office of Guilak’s close colleague, Larry Bonassar.“I was like, man, I should probably start to network a little bit. I thought I was being clever,” Matthews said. “It was early morning, and he happened to be in his office. We sat down and talked for an hour or two, which, you don’t know when you’re 18, but that’s a huge commitment for a professor. And I guess it was a sign of what was to come.”Two years later, as a sophomore mechanical engineering major, Matthews came back to Bonassar with a specific ask. Was there a research project Matthews could work on?What Bonassar had, in his own words, was “a crazy idea” that he’d been kicking around for a long time but hadn’t been able to investigate. While his lab had successfully demonstrated 3D printing living tissue with homogeneous materials for replacement ears and cartilage, the next step was doing that for more sophisticated, functional structures, i.e., organs and skin.The project had a greater scope than what an undergrad would traditionally tackle, but Matthews found the challenge compelling. That’s not to say it wasn’t a little daunting.&nbsp;“It was my first experience really reading a research paper,” Matthews said. “I didn’t know what I was reading. But I was like, you know, I’m gonna try it.”Developing a new method wouldn’t just be an academic exercise, he recognized, but a “very applied, practically useful device, with implications in industry for manufacturing tissue at scale.”&nbsp;Bonassar and Matthews brainstormed ideas and hit upon an alternate mode of sensing: dielectric impedance spectroscopy (DIS), whereby a pair of electrodes creates a current. Because cell membranes are not permeable to charge, the current would be forced to go around the cells as their internal ions became polarized. That combination of effects would create a unique impedance signature for each cell that could ultimately be measured to determine the number of cells and their size, intactness and density.It was a smart design, indeed. It just needed to be built. And tested. And studied.Because Matthews was deep in his undergraduate studies, he didn’t have much free time during the semester to get the project off the ground. So he applied for, and received, a grant from <a href="https://www.engineering.cornell.edu/eli" target="_blank">Engineering Learning Initiatives</a> to work in the lab through the summer of 2019.In addition to covering his living and research expenses, the grant carried some extra cachet. It came from a donation made by Bill Nye.&nbsp;As the 2019 Nye Fellow, Matthews had an opportunity to meet the “Science Guy” himself that summer and tell him a bit about the smart syringe and its potential impact.“He said, ‘Well, go on and <a href="https://news.cornell.edu/stories/2024/04/slide-rules-sundials-and-comedy-bill-nye-hails-scientific-solutions" target="_blank">change the world</a>.’ It left an impression on me, for sure,” Matthews said. “That was a great little introduction to my research work, to have a celebrity backing it.”&nbsp;<h2>‘Something kind of special’</h2>By the end of fall 2019, Matthews had constructed a protype, conducted the initial experiments and presented the work-in-progress to the Biomedical Engineering Society in Philadelphia. But the ensuing months would not go as smoothly. In March 2020, the pandemic hit, derailing all on-campus research and activities. So Matthews pivoted and focused on data analysis and reviewing the relevant literature to put his experimental results in context.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1726702480144-0918_syringe2.jpg" style="width: 100%px;" class="fr-fic fr-dib">A smart sensor that attaches to the tip of a syringe can measure, in real time, the concentration and viability of the cells that pass through it – a potential breakthrough for biomedical 3D printing and cell therapy. Jason Koski/Cornell University“You don’t just get a yes or no answer from the device. It doesn’t just tell you if it worked or not. You get back waveforms, signal, there’s going to be noise, artifacts, and you have to interpret that in the context of the physical chemistry and the algorithms you used to process it,” Matthews said. “It was not a pure mechanical engineering problem. It pulled from so many different fields. You had to know, at some level of competency, control theory, and interface theory from chemistry, fluid dynamics. All these disciplines came together, and you had to be able to attend to them individually.”By the time Matthews was ready to graduate, in spring 2021, “we knew we had something kind of special,” Bonassar said. “That’s when we disclosed it to Cornell and filed the provisional patents.”Within three years of submitting their application, the patent was issued in June. By Bonassar’s count, this is his 25th patent. He’s never had one approved so quickly.“We’ve had patents that have taken us seven years to get through the process. For people in the know, two to three years from initial application to issue is quite fast,” he said. “What that often means is there isn’t much like it, and we didn’t get hit with, ‘Oh, it looks like seven other people have tried things like this, why is yours different?’ My impression is there’s really not much out there where people are doing assessment of cell properties at these really high concentrations.”In addition to capturing 2,000 different measurements in real time, the device creates a series of feedback loops that can help control the flow rate and temperature as cell viability changes. That in itself would be revolutionary for the bioprinting field, but the device has applications in other fields as well. Hospitals in developing countries could use it for getting instant blood counts on patients. Doctors could deliver precise infusions of cells, bone marrow and lipos for cell therapy, treating cancer or for regenerative medicine.“If we can measure it, then instead of saying, ‘Well, deliver 10 CCs of this solution that we think has a million cells per CC,’ you can now make a device that just delivers 10 million cells and then stops,” Bonassar said.Bonassar’s lab has collaborated with Dr. Jason Spector, professor of plastic surgery at Weill Cornell Medicine, to demonstrate how the smart syringe can assist in clinic samples.After Matthews graduated from Cornell, he headed to Georgia Tech, where he extended what he had learned from the smart syringe project into developing more next-generation medical devices, such as soft, wearable biosensors and remote telemedicine platforms for optimizing strength and metabolism, and cardiovascular monitoring. Even when the technology was different, the underlying skills were the same: problem solving, interpreting data, presenting findings to a skeptical audience.That research experience, in turn, led him to his current role working for GE HealthCare, developing large neural networks for optimizing patient care.&nbsp;Now, he and Bonassar are mulling their options to commercialize the smart syringe, although in many ways, it’s already been a success.“I wouldn’t be here, privileged to do what I do, without having worked on the smart syringe project, specifically with Larry,” Matthews said. “He grants a lot of autonomy, he trusts in his students, and that comes through to the student. Larry was always there as a fallback to help steer the project when it began to drift. I remember he said a design I had was ‘orthogonal,’ meaning it was perpendicular to the direction we should be going. I had never had anyone tell me that before. It was delivered so well, I wasn’t upset by it. It was like, OK, let’s try something different. It was sort of a humbling experience in that way.”The time he spent in Bonassar’s lab paid off in other ways, too. That was where, in the summer of 2019, he first met another undergraduate researcher, Emily Jiang ’20.&nbsp;She is now his fiancée.“That’s a little happy ending there,” Matthews said.

Lawrence Bonassar, the Daljit S. and Elaine Sarkaria Professor in Biomedical Engineering and in Mechanical and Aerospace Engineering, and doctoral student Alicia Matavosian examine a smart sensor developed with Jared Matthews ’21.

Researchers created a smart sensor that attaches to the tip of a syringe to measure, in real time, the concentration and viability of the cells that pass through it – a device that would enable surgeons and biomanufacturers to produce higher quality

From lab to patent: Undergrad creates smart syringe for bioprinting

In this episode, we discuss how an ex-apple engineer who worked on the apple watch got inspired to create a smart patch for treating psoriasis.<iframe height="200px" width="100%" frameborder="no" scrolling="no" seamless="" src="https://player.simplecast.com/779ab725-9c50-48f5-9e38-00be474265f5?dark=false" class="fr-draggable" data-lf-form-tracking-inspected-kn9eq4roawkarlvp="true" data-lf-yt-playback-inspected-kn9eq4roawkarlvp="true" data-lf-vimeo-playback-inspected-kn9eq4roawkarlvp="true"></iframe><hr><h3 id="isPasted">EPISODE NOTES</h3>(0:50) - <a href="https://www.wevolver.com/article/to-heal-skin-scientists-invent-living-bioelectronics" target="_blank">To Heal Skin, Scientists Invent Living Bioelectronics</a>Become a founding reader of our newsletter: <a href="http://read.thenextbyte.com/" target="_blank">http://read.thenextbyte.com/</a><hr><h2 data-attrid="title" data-local-attribute="d3bn" data-ved="2ahUKEwiBhLnmu4aAAxVmwjgGHcDWC38Q3B0oAXoECEgQEQ" id="isPasted">Transcript</h2>What's up folks, in today's episode we're talking about the future of skincare. And if you're frustrated like me with traditional skincare treatments, they feel inconsistent, you're not sure if they're working, you're not able to quickly measure like is this working or not, you're going to be really excited about this because we're talking about this ex-Apple engineer who originally helped create the Apple Watch and is now creating the super smart patch which is basically the Apple Watch for skincare that both heals and tracks your skin's health.I'm Daniel, and I'm Farbod. And this is the NextByte Podcast. Every week, we explore interesting and impactful tech and engineering content from Wevolver.com and deliver it to you in bite sized episodes that are easy to understand, regardless of your background.&nbsp;Daniel:&nbsp;What's up folks? Like we said, today we're talking all about the ex-Apple engineer who's creating the Apple watch to help everyone get clear skin. Pretty interesting story behind this one.Farbod:&nbsp;You know we love episodes with a good story.Daniel:&nbsp;We always love episodes and really the engineers and creators behind awesome technology when they've got an awesome story. And that's pretty much what compelled us to talk about this one. Dr. Simiao Niu who was troubled by psoriasis in his youth. I can relate. I've also been troubled by psoriasis.Farbod:&nbsp;It's a personal episode.Daniel:&nbsp;Yeah, it hits deep in my heart and on patches on my knees and elbows as well. But Dr. Niu has struggled with inconsistent treatments, treatment results, lack of feedback. I can understand as an engineer, right? It's really challenging to like feel like some aspects of your health are really easily quantitatively measured. Like, oh, I want to improve my blood cholesterol. Well, you can just go get another complete blood count and compare your cholesterol from the moment before and be like, oh, my cholesterol has improved. Or if you'd be like, oh, I wanna lose weight, you get on a diet routine, you work out, you lose weight, you step on the scale, bang. You can measure the product of your work. But with treating psoriasis, it's really challenging to like quantitatively measure how well to tell what it's doing, is it improving, is the treatment effective, or are the side effects not worth it? So, his goal as an engineer is to kind of create an electronic patch that treats skin blemishes like psoriasis and provides continuous feedback.Farbod: This is a goal; I think is worth saying. It kind of, it was inspired by the work he was doing in Apple.Daniel: That's what I was going to say is like, I kind of alluded to it earlier, right? He helped create the Apple watch. Yeah. He's going to create the Apple watch for, for clear skin. But it's really interesting, Dr. New worked at Apple on the Apple watch, creating electronics specifically for health monitoring and measuring to do two things, right? To one help measure health and then two improve it. That seems like a theme here. He wants to make sure that you make devices that one measure health and then to improve it. He wants to create a wearable device for skin ailments that do this two, but when he was at Apple, he was working on, I think it was the temperature sensor and the ECG sensor that are inside the Apple Watch on my wrist right now. And when he was at Apple, he was developing these wearables that again, one, help measure how health is doing and two, help you improve it. He created the ECG sensor for Apple Watch and literally got like hundreds and hundreds of thank you notes shipped to his desk from people who were thanking him for being like, oh, thank you to the engineer who helped develop this ECG sensor it helped save my life by detecting this arrhythmia or this heart attack, et cetera. And that really inspired him to be like, Whoa, we're able to do this for some types of health ailments. And granted these were life-saving ones, but can we do the same thing for this problem that's been plaguing me for my whole life on my skin? Yeah. Is there something similar we can do using similar technology? And that, that kind of is like his, his so what, or his why story motivating him to make this development.Farbod:&nbsp;Yeah. And you know, the beauty of the Apple Watch is that it gives you a lot of like holistic snapshots. Like, it gives you inside about your, the healthiness of your sleep, etc, etc. But at the core of it, it really boils down to your heart health. And that's what it's actively measuring. And the messages that you were mentioning, it was because they were able to pick up these like irregular heartbeat patterns and pick up on, I'm going to butcher saying this, Atrial Fibrillation which is like a silent killer that most folks cannot detect, but the Apple Watch does. So, hundreds of people literally got notifications of like, hey, you're at risk or there's something abnormal going on, go to the doctor. And that's what ended up saving their lives. So, it was really easy for him to make that connection of, oh, here's like one specific condition that we were monitoring for one muscle, which was the heart. How can we extract that same concept and now apply it to the psoriasis problem? I mean, let's just jump right into the, what's going on here, the solution. What do you think?Daniel:&nbsp;Yeah, I think it's the perfect part, right? So, Dr. Niu leaves Apple, goes to Rutgers University, previous background, got his PhD from Georgia Tech in both materials engineering and in electronics.Farbod:&nbsp;Jack of all trades.Daniel: I know, Jack of all trades. And so, combining these two worlds along with the world of bacteria, the world of living biology is able to combine advanced materials, advanced electronics and living cells to create this awesome patch that is designed to treat psoriasis but can also potentially help treat other skin conditions. And it's about one inch in diameter. It's really wafer thin and like I said the main aspects here is the electronic chip, the bacterial cells and then a hydrogel starch that's made from gelatin that helps hold the bacterial cells on the electronic chip.Farbod: And it's the first of its kind. I think that's also worth saying. There's a lot of bio-electronic strips and patches and whatnot, but typically the way they work that the French treats them from this is that you have the electronics embedded in some sort of a flexible polymer that you're just strapping on yourself. But what you just pointed out, that little gel, which is helping distribute the bacteria cells that are in there, that's what's giving it a living component. So, this is a first-generation living bio-electronic patch.Daniel:&nbsp;Yeah, not just bio-electronic. It's living bio-electronic. And I thought it's pretty interesting diving into the bacteria on this. I thought, you know, counterproductive to have bacteria.Farbod: Same. I was so confused.Daniel:&nbsp;How does this treat something like psoriasis? But I think it's really awesome. They targeted the specific type of bacteria called S epidermidis, which is already a part of the skin microbiome and is part of your skin's natural response to things like rashes on your skin. And it actually thrives in the oils on your skin. And one of the things that they found on trials in mice is that if they have a skin condition like psoriasis, introducing additional S epidermidis bacteria helps reduce inflammation. So, it helps reduce some of the nasty effects from psoriasis like itching, like pain, like swelling in the local area of the disease. Because these bacteria actually secrete anti-inflammatory compounds when the patch is placed on the skin. So, you basically got this awesome method of treating psoriasis. You've also got a flexible PCB that's kind of like the skeleton of the device holding it all together. This flexible circuit monitors the resistance of your skin, the temperature of your skin and the humidity of the skin, which is transmit, this data is transmitted wirely to your computer, to your cell phone, and essentially between understanding the relationship between the bacteria that are on this skin, emitting these anti-inflammatory compounds, as well as these different signals, again, skin resistance, skin temperature, skin humidity, they can start to measure how the effectiveness of the bacteria is at reducing the symptoms associated with psoriasis.Farbod:&nbsp;Yeah. And it's interesting because they started testing on rats, on rats that had psoriasis-like symptoms or conditions, and they are seeing, they're able to demonstrate that this patch does have improvements to those conditions. So now their next step is to actually move forward with human testing. It's possible that folks like you will be able to access this technology in the not-so-distant future, which is pretty promising.Daniel:&nbsp;Yeah, I'm really excited about this. And one of the things that I think is awesome is they, you know, we talk about this with a lot of technologies in a similar space, once, once you've taken a novel approach, the best thing to do is look for like, all right, did my thesis or did my hypothesis work for this? What application I wanted to did this living by electronic device help with treating psoriasis? Yes, it did. Now in this case, have we also created a platform that can help treat on a bunch of other similar skin conditions or other conditions. In this case, they have a strong hypothesis that they think so as well. So not only have they developed something to help treat psoriasis, they understand that the same epidermis bacteria secreting anti-inflammatory compounds could really help with healing of really big trauma to the skin. So, like think really, really serious wounds or maybe your wound from a surgery or something like that, you can use that similar bacteria to help promote healing. They also said it can help with skin cancer after the cancer cells have been removed, can help the localized area to heal faster. And more so than just promoting the healing, using the bacteria they said for doctors, it could be really, really interesting to get continuous feedback and real-time monitoring on how the wound is healing using this data that comes along, along with the living bio electronic patch, the electronic part of that collecting a lot of data over time can help doctors understand how wounds are healing and whether it deserves extra attention or not.Farbod:&nbsp;And I'm wondering like if they find other bacterias that could be helpful for different conditions, it seems like this platform is flexible enough to adopt those new bacteria as well.Daniel:&nbsp;Well, yeah. And it's the touching back at Dr. Nui, advanced materials education, right. This hydrogel that's made from starch and gelatin is kind of what promotes the fact that these bacteria can live in this hydrogel and then also be compatible with the skin. Like you're saying, I'm wondering if there's other living organisms that could be introduced to this bacterial cocktail essentially and promote different types of effects. Maybe you want one that's antifungal to help fight a fungal infection or maybe you want a different type of bacteria that helps combat other bacterial infections or maybe you just want a higher concentration of S epidermidis to help reduce inflammation for a different type of condition.Farbod:&nbsp;Yeah, no I agree. What do you say you wrap up this little episode?Daniel:&nbsp;Well, I will say right before we do this, I think that one of the things I want to start doing in the podcast, we kind of get like, we've gotten called out a couple of times for being like, oh, you're just tech cheerleaders. You only talk about the pros, you don't talk about the cons. So, I'm gonna be very purposeful, I think, moving forward to try and talk about some of the pros and some of the cons, summarizing the so what. Because I feel like we touch on the pros and the cons every single time, but just to like dangle that food out there for the haters a little bit, I understand. I also get frustrated if I feel like people are just tech cheerleaders, that's not what we're here to do.Farbod:&nbsp;It's tough when you're so excited about a topic like this, I'll say that.Daniel:&nbsp;We can be futurists, but we can also be measured futurists.Farbod: I hear you. I hear you.Daniel:&nbsp;So, in this case, I'm going to hang it out there for you, the haters, the pros, right? This device offers a novel approach to bioelectronics. It allows electronics to incorporate living cells, can allow patients and doctors to monitor their healing process as well using the electronic sensors. This can lead to more effective and personalized treatments. But the cons, clinical trials are needed first before this can be used on humans. It's only been tested on rats and beyond clinical trials, FDA approval is required for this type of medical device before commercialization. This could be a really lengthy process. So, for folks with psoriasis like myself, who are excited by this, maybe you got to sign up for the clinical trial to get access to it, or it could be a couple of years before we see this thing in the field, if it gets approved. So again, for you haters out there, the pros and the cons laid out perfectly for you. Just want to make sure that we're not, we're not being paid by anyone to talk about this and chill it.Farbod: We do it for the love of the game.Daniel:&nbsp;We do it for the love of the game. In this case, we're talking about the pros and the cons of the game.Farbod: Exactly. Good man. I appreciate that.Daniel:&nbsp;All right, now that I've gotten that off my chest, I'm happy to wrap up this episode, man, with a quick recap.Farbod: Let's do it.Daniel:&nbsp;This Apple engineer who helped create the Apple Watch wants to help everyone get clear skin. His goal was to create an electronic patch that treats skin blemishes like psoriasis, which I have on my knee and provide continuous feedback to patients as well to understand how their health is doing. But traditional treatments are inconsistent. They don't offer real-time monitoring and they're not easily measurable. So, he took his background from Apple, creating the Apple Watch, combined electronics with anti-inflammatory bacteria to create a tiny patch that can monitor skin conditions and heal blemishes quickly. It's like having an Apple Watch, but for skincare, that both heals and tracks the condition of your skin. And that's why this tiny microchip designed by an Apple engineer is gonna be the future of getting clear skin.Farbod: You have me at Apple Watch for skincare. That's gonna be the episode title.Daniel:&nbsp;Boom, boom, boom, boom, boom.Farbod:&nbsp;All right, folks, thank you so much for listening. And as always, we'll catch you in the next one.Daniel:&nbsp;Peace.<hr id="isPasted">As always, you can find these and other interesting &amp; impactful engineering articles on Wevolver.com.To learn more about this show, please visit our<a href="https://www.wevolver.com/profile/the.next.byte" target="_blank">&nbsp;shows page</a>. By following the page, you will get automatic updates by email when a new show is published. Be sure to give us a follow and review on<a href="https://podcasts.apple.com/nl/podcast/the-next-byte/id1548255861?l=en" target="_blank" rel="nofollow">&nbsp;Apple</a> podcasts,<a href="https://open.spotify.com/show/6lPPsRtegnivsRUEsQ09R7?si=IPMiah7xT_apJtPjqvXMlA" target="_blank" rel="nofollow">&nbsp;Spotify</a>, and most of your favorite podcast platforms!--The Next Byte: We're two engineers on a mission to simplify complex science &amp; technology, making it easy to understand. In each episode of our show, we dive into world-changing tech (such as AI, robotics, 3D printing, IoT, &amp; much more), all while keeping it entertaining &amp; engaging along the way.

In this episode, we discuss how an ex-apple engineer who worked on the apple watch got inspired to create a smart patch for treating psoriasis.

Podcast: Ex-Apple Engineer Creates Skincare Smart Patches

<section id="isPasted">Most people, when they think about pythons, visualize the huge snake constricting and swallowing victims whole. But did you know that pythons initially hold onto their prey with their sharp, backward-curving teeth? Medical researchers have long been aware that these teeth are perfect for grasping soft tissue rather than cutting through it, but no one has yet been able to put this concept into surgical practice. Over the years, mimicking these teeth for use in surgery has been a frequent topic of discussion in the lab of&nbsp;<a href="https://www.columbiaortho.org/profile/stavros-thomopoulos-phd" rel="nofollow" target="_blank">Dr. Stavros Thomopoulos</a>, a professor of&nbsp;<a href="https://www.columbiaortho.org/" rel="nofollow" target="_blank">orthopedics</a> and&nbsp;<a href="https://bme.columbia.edu/" rel="nofollow" target="_blank">biomedical engineering&nbsp;</a>at Columbia University.</section><section><h2>Biomimicry key to new study</h2>A leading researcher focused on the development and regeneration of the tendon-to-bone attachment, Thomopoulos is particularly interested in advancing tendon-to-bone repair, necessary for rotator cuff repair and anterior cruciate ligament reconstruction.&nbsp;<a href="https://www.science.org/doi/10.1126/sciadv.adl5270" rel="nofollow" target="_blank">In a paper published today</a> by Science Advances, his team reports that they have developed a python-tooth-inspired device as a supplement to current rotator cuff suture repair, and found that it nearly doubled repair strength.&nbsp;“As we grow older, more than half of us will experience a rotator cuff tear leading to shoulder pain and decreased mobility,” said Thomopoulos, who has joint appointments at&nbsp;<a href="https://www.engineering.columbia.edu/" rel="nofollow" target="_blank">Columbia Engineering</a> and Columbia’s&nbsp;<a href="https://www.vagelos.columbia.edu/" rel="nofollow" target="_blank">Vagelos College of Physicians and Surgeons</a> as the Robert E. Carroll and Jane Chace Carroll Professor of Biomechanics (in Orthopedic Surgery and Biomedical Engineering). “The best medical intervention is rotator cuff surgery, but a remarkably high percentage of these repairs will fail within just a couple of months. Our biomimetic approach following the design of python teeth helps to reattach tendons to bone more securely. The device not only augments the strength of the repair but can also be customized to the patient. We’re really excited about the potential of our device to improve the care of rotator cuff injuries.”</section><section><h2>Rotator cuff injuries</h2>Among the most prevalent tendon injuries, rotator cuff tears affect more than 17 million people in the United States each year. The incidence of injury increases with age: more than 40% of the population over 65 years old experience a rotator cuff tear.&nbsp;Because rotator cuff tears typically occur at the tendon-to-bone insertion site, rotator cuff repair is aimed at anatomically restoring the tendon attachment. Surgical repair is the primary treatment for restoring shoulder function, with more than 600,000 procedures performed annually in the United States at a cost of $3 billion.&nbsp;However, successfully reattaching tendon to bone remains a significant clinical challenge. High failure rates occur following surgery, with rates increasing with patient age and tear severity. These rates range from 20% in younger patients with minor tears to a staggering 94% in elderly patients with massive tears. The most common failure of rotator cuff repairs is sutures tearing through the tendon at the two or four grasping points where forces concentrate.While there have been advancements in rotator cuff repair techniques over the past 20 years, the fundamental approach of sewing two tissues together has remained largely unchanged, still relying on sutures transferring tension at high-stress grasping points. Following tendon-to-bone reattachment surgery, sutures can tear through tendons at these points of high stress, a phenomenon known as “suture pull-through” or “cheesewiring,” leading to repair-site gapping or rupturing. “We decided to see if we could develop a device that mimics the shape of python teeth, that would effectively grasp soft tissues without tearing, and help reduce the risk of tendon re-tearing after rotator cuff repair,” said Iden Kurtaliaj, the study’s lead author and a former biomedical engineering PhD student in the&nbsp;<a href="https://www.columbiaortho.org/thomopoulos-lab" rel="nofollow" target="_blank">Thomopoulos’ lab</a>.</section><section><h2>The device</h2>The team’s original idea was to copy the shape of python teeth, but they went much further, using simulations, 3D printing, and&nbsp;ex vivo experiments on cadavers to explore the relationship between tooth shape and grasping vs. cutting mechanics. Kurtaliaj manufactured a range of tooth designs, optimized individual teeth, arrays of teeth, and finally a rotator cuff-specific array of teeth. The end result was a biomimetic device, made of a biocompatible resin -- an array of teeth atop a curved base -- capable of grasping, not cutting, tendon. The teeth are relatively small -- 3mm high for a human rotator cuff, about half the length of a standard staple -- so that they won’t poke through the tendon. The base can be customized via 3D printing to match the patient-specific curvature of the humeral head at the supraspinatus tendon attachment site (the most commonly torn rotator cuff tendon).“We designed it specifically so that surgeons won’t need to abandon their current approach--they can simply add the device and increase the strength of their repair,” Kurtaliaj noted.</section><section><h2>The team</h2>Kurtaliaj led the research as a PhD student under the mentorship of Drs. Stavros Thomopoulos and&nbsp;<a href="https://engineering.wustl.edu/faculty/Guy-Genin.html" rel="nofollow" target="_blank">Guy Genin,</a> the Harold and Kathleen Faught Professor of Mechanical Engineering at Washington University in St. Louis, with input for clinical implementation from&nbsp;<a href="https://www.columbiaortho.org/profile/william-n-levine-md" rel="nofollow" target="_blank">Dr. William Levine</a>, chair of the Department of Orthopedic Surgery at Columbia University's College of Physicians and Surgeons.“Due to our laboratory's close collaboration with orthopedic surgeons, we were especially fortunate to get input from Dr. Levine, along with other surgeons at Columbia, throughout the device's design development process,” said Thomopoulos.</section><section><h2>Next steps</h2>The researchers are now working to develop a bioabsorbable version of the device that would degrade as the rotator cuff heals back to bone, further enhancing its clinical applicability. They are also preparing for a pre-submission meeting with the FDA to facilitate the transition of their device into the market.</section>

Schematic of the python tooth-inspired device interposed between tendon a bone significantly enhances standard rotator cuff repair. Credit: Iden Kurtaliaj/Columbia Engineering

Columbia University team uses biomimicry to create a device that may reduce the risk of rotator cuff re-tearing in patients.

New Device Inspired by Python Teeth Doubles Strength of Rotator Cuff Repairs

Human brain diseases, such as Parkinson’s disease, involve damage in more than one region of the brain, requiring technology that could precisely and flexibly address all affected regions simultaneously. Researchers at Washington University in St. Louis have developed a noninvasive technology combining a holographic acoustic device with genetic engineering that allows them to precisely target affected neurons in the brain, creating the potential to precisely modulate selected cell types in multiple diseased brain regions.&nbsp;Hong Chen, associate professor of biomedical engineering in the McKelvey School of Engineering and of neurosurgery in the School of Medicine, and her team created AhSonogenetics, or Airy-beam holographic sonogenetics, a technique that uses a noninvasive wearable ultrasound device to alter genetically selected neurons in the brains of mice. Results of the proof-of-concept study were published in&nbsp;Proceedings of the National Academy of Sciences June 17, 2024.&nbsp;AhSonogenetics brings together several of Chen’s group’s recent advances into one technology. In 2021, she and her team launched&nbsp;<a href="https://engineering.wustl.edu/news/2021/First-in-class-tool-for-potential-treatment-of-brain-disorders.html" target="_blank">Sonogenetics</a>, a method that uses focused ultrasound to deliver a viral construct containing ultrasound-sensitive ion channels to genetically selected neurons in the brain. They use low-intensity focused ultrasound to deliver a small burst of warmth, which opens the ion channels and activates the neurons. Chen’s team was the first to show that&nbsp;<a href="https://engineering.wustl.edu/news/2021/First-in-class-tool-for-potential-treatment-of-brain-disorders.html" target="_blank">sonogenetics could modulate the behavior of freely moving mice</a>.In 2022, she and members of her lab designed and 3D-printed a flexible and versatile tool known as an&nbsp;<a href="https://engineering.wustl.edu/news/2022/New-practical-method-of-producing-Airy-beams-could-enhance-ultrasound.html" target="_blank">Airy beam-enabled binary acoustic metasurface</a> that allowed them to manipulate ultrasound beams. She also is developing&nbsp;<a href="https://engineering.wustl.edu/news/2023/Genetic-engineering-delivered-with-ultrasound-studied-to-treat-brain-disorders.html" target="_blank">Sonogenetics 2.0</a>, which combines the advantage of ultrasound and genetic engineering to modulate defined neurons noninvasively and precisely in the brains of humans and animals. AhSonogenetics brings them together as a potential method to intervene in neurodegenerative diseases.&nbsp;“By enabling precise and flexible cell-type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders,” Chen said.&nbsp;Sonogenetics gives researchers a way to precisely control the brains, while airy-beam technology allows researchers to bend or steer the sound waves to generate arbitrary beam patterns inside the brain with a high spatial resolution. Yaoheng (Mack) Yang, a postdoctoral research associate who earned a doctorate in biomedical engineering from McKelvey Engineering in 2022, said the technology gives the researchers three unique advantages.“Airy beam is the technology that can give us precise targeting of a smaller region than conventional technology, the flexibility to steer to the targeted brain regions, and to target multiple brain regions simultaneously,” Yang said.Chen and her team, including first authors Zhongtao Hu, a former postdoctoral research associate, and Yang, designed each Airy-beam metasurface individually as the foundation for wearable ultrasound devices that were tailored for different applications and for precise locations in the brain.Chen’s team tested the technique on a mouse model of Parkinson’s disease. With AhSonogenetics, they were able to stimulate two brain regions simultaneously in a single mouse, eliminating the need for multiple implants or interventions. This stimulation alleviated Parkinson’s-related motor deficits in the mouse model, including slow movements, difficulty walking and freezing behaviors.The team’s Airy-beam device overcomes some of the limits of sonogenetics, including tailoring the design of the device to target specific brain locations, as well as incorporating the flexibility to adjust target locations in a single brain.Hu said the device, which costs roughly $50 to make, can be tailored in size to fit various brain sizes, expanding its potential applications.&nbsp;“This technology can be used as a research platform to speed neuroscience research because of the capability to flexibly target different brain regions,” Hu said. “The affordability and ease of fabrication lower the barriers to the widespread adoption of our proposed devices by the research community for neuromodulation applications.”<hr>Hu Z, Yang Y, Gong Y, Chukwu C, Ye D, Yue Y, Yuan J, Kravitz AV, Chen H. Airy-beam holographic sonogenetics for advancing neuromodulation precision and flexibility. Proceedings of the National Academy of Sciences June 17, 2024, DOI:&nbsp;<a href="https://doi.org/10.1073/pnas.2402200121" target="_blank">10.1073/pnas.2402200121</a>.&nbsp;Funding for this research was provided by the National Institutes of Health (R01NS12846, R01MH116981, UG3MH126861, R01EB027223, R01EB030102).The design file for the Airy-beam holographic transducer is available on GitHub:&nbsp;<a href="https://github.com/ChenUltrasoundLabWUSTL/AiryBeam_Lens_Design" target="_blank">https://github.com/ChenUltrasoundLabWUSTL/AiryBeam_Lens_Design</a>.

McKelvey School of Engineering researchers have developed a noninvasive technology combining a holographic acoustic device with genetic engineering that allows them to precisely target affected neurons in the brain, creating the potential to precisely modulate selected cell types in multiple diseased brain regions. (Credit: Yaoheng Yang)

Hong Chen and her lab develop wearable device that modulates brain neurons in mice

New technology allows researchers to precisely, flexibly modulate brain

This article was discussed in our <a href="https://www.wevolver.com/profile/the.next.byte" rel="noopener noreferrer" target="_blank">Next Byte podcast</a>.&nbsp;<iframe height="200px" width="100%" frameborder="no" scrolling="no" seamless="" src="https://player.simplecast.com/779ab725-9c50-48f5-9e38-00be474265f5?dark=false" class="fr-draggable" data-lf-form-tracking-inspected-kn9eq4roawkarlvp="true" data-lf-yt-playback-inspected-kn9eq4roawkarlvp="true" data-lf-vimeo-playback-inspected-kn9eq4roawkarlvp="true"></iframe> The full article will continue below.<hr>For much of his childhood, Simiao Niu was troubled by psoriasis, a chronic, often painful skin condition, mostly on his arms.Sometimes, the prescribed ointment worked and treated the inflamed, red areas produced by the disease. But he was never sure if he was using enough, whether the skin irritation was healing and when he should stop treatment.Years later, as an engineer on the team at Apple Inc. that devised the electronics in Apple watches monitoring heart rhythm, Niu had a revelation: Could a similar wearable electronic device be developed to treat skin ailments such as psoriasis and provide patients with continuous feedback?Now,&nbsp;<a href="https://bme.rutgers.edu/simiao-niu" target="_blank">Niu</a>, an assistant professor of biomedical engineering in the School of Engineering at Rutgers-New Brunswick, has played a crucial role in the development of the kind of device that he dreamed of: a unique prototype of what he and his research collaborators are calling a “living bioelectronic” designed to treat psoriasis.<a href="https://www.science.org/doi/10.1126/science.adl1102" target="_blank">Describing</a>&nbsp;the advance in Science magazine, Niu and collaborators, including scientists at the University of Chicago led by Bozhi Tian and Columbia University, reported developing a patch – a combination of advanced electronics, living cells and hydrogel – that is showing efficacy in experiments in mice.The patch represents not only a potential treatment for psoriasis, but a new technology platform to deliver treatments for medical needs as diverse as wounds and, potentially, various skin cancers, Niu said.“We were looking for a new type of device that combines sensing and treatment for managing skin inflammation diseases like psoriasis,” Niu said. “We found that by combining living bacteria, flexible electronics and adhesive skin interface materials, we were able to create a new type of device.”The circular patch is about 1 inch in diameter and wafer thin. The patch contains electronic chips, bacterial cells and a gel made from starch and gelatin. Tests in mice conducted by the research team showed that the device could continuously monitor and improve psoriasis-like symptoms without irritating skin.The device, Niu said, is a leap forward from conventional bioelectronics, which are generally composed of electronic components that are encased in a soft synthetic layer that reduces irritation when in contact with the body. The electrode patches placed on a patient’s chest for an electrocardiogram are examples of conventional devices.Niu’s invention could be seen as a “living drug,” he said, in that it incorporates living cells as part of its therapy. S. epidermidis,&nbsp;which lives on human skin and has been shown to reduce inflammation, is incorporated into the device’s gel casing. A thin, flexible printed circuit forms the skeleton of the device.When the device is placed on skin, the bacteria secrete compounds that reduce inflammation, while sensors in the flexible circuits monitor the skin for signals indicating healing, such as skin impedance, temperature and humidity. The data collected by the circuits is beamed wirelessly to a computer or a cell phone, a process that would allow patients to monitor their healing process.During his years at Apple, before he joined Rutgers faculty in 2022, Niu and other engineers were forwarded hundreds of thank-you notes that had been sent to the chief executive’s office. The customers wrote to credit their Apple watches with saving their lives, Niu said. The watches’ built-in heart rate monitors pointed to a condition – an arrhythmia known as atrial fibrillation – the customers said they didn’t know they had. Atrial fibrillation can lead to strokes if left untreated.“When you produce the kinds of things that positively affect people’s lives, you feel very proud,” Niu said. “That is something that inspires me a lot and motivates me to do my current research.”Clinical trials to test the device on human patients must come next, Niu said, as the first step toward commercialization. Once there is evidence of positive results with minimum side effects, the inventors would apply for FDA approval in order to bring the device to market, Niu said.Other authors of the study from Rutgers included Fuying Dong and Chi Han, two graduate students in the Department of Biomedical Engineering in the School of Engineering.

Assistant Professor of Biomedical Engineering Simiao Niu (center) works with graduate students Fuying Dong (left) and Chi Han (right) on a new "living bioelectronic" medical device they developed that combines advanced electronics, living cells and hydrogels. S. Niu

Rutgers–New Brunswick engineer and students create patch that combines sensors and bacteria to interact with the body

To Heal Skin, Scientists Invent Living Bioelectronics

There are some things in life you can watch and then never unwatch,” said<a href="https://profiles.stanford.edu/manu-prakash" data-extlink="" target="_blank">&nbsp;Manu Prakash</a>, associate professor of bioengineering at Stanford University, calling up a video of his latest fascination, the single-cell organism Lacrymaria olor, a free-living protist he stumbled upon playing with his paper<a href="https://foldscope.com/" data-extlink="" target="_blank">&nbsp;Foldscope</a>.&nbsp;“It’s … just … it’s mesmerizing.”“From the minute Manu showed it to me, I have just been transfixed by this cell,” said Eliott Flaum, a graduate student in the “curiosity-driven”<a href="https://web.stanford.edu/group/prakash-lab/cgi-bin/labsite/" data-extlink="" target="_blank">&nbsp;Prakash Lab</a>. Prakash and Flaum spent the last seven years studying Lacrymaria olor’s&nbsp;every move and recently published<a href="https://www.science.org/doi/10.1126/science.adk5511" data-extlink="" target="_blank">&nbsp;a paper</a> on their work in Science.“The first time I came back with a fluorescence micrograph, it was just breathtaking,” Flaum said. “That image is in the paper.”Beautiful and mesmerizing,&nbsp;L. olor is actually&nbsp;Science’s latest cover art.The video Prakash queued up reveals why this organism is much more than a pretty picture: a single teardrop-shaped cell swims in a droplet of pond water. In an instant, a long, thin “neck” projects out from the bulbous lower end. And it keeps going. And going. Then, just as quickly, the neck retracts back, as if nothing had happened.In seconds, a cell that was just 40 microns tip-to-tail sprouted a neck that extended 1500 microns or more out into the world. It is the equivalent of a 6-foot human projecting its head more than 200 feet. All from a cell without a nervous system.“It is incredibly complex behavior,” Prakash said with a smile.<iframe width="640" height="360" src="https://www.youtube.com/embed/LZArEEBeMpI?&amp;wmode=opaque&amp;rel=0&amp;enablejsapi=1&amp;origin=https://www.wevolver.com" frameborder="0" allowfullscreen="" class="fr-draggable" data-lf-form-tracking-inspected-kn9eq4roawkarlvp="true" data-lf-yt-playback-inspected-kn9eq4roawkarlvp="true" data-lf-vimeo-playback-inspected-kn9eq4roawkarlvp="true"></iframe>Video courtesy of Prakash Lab/Andrew Myers<h2 id="isPasted">Form is function</h2>L. olor has landed on the cover of&nbsp;Science because Prakash and Flaum have discovered in this behavior a new geometric mechanism previously unknown in biology. And they are the first to explain how such a simple cell can produce such incredible morphodynamics, beautiful folding and unfolding – aka origami – at the scale of a single cell, time and again without fail.It is geometry.&nbsp;L. olor’s behavior is encoded in its cytoskeletal structure, just like human behavior is encoded in neural circuits. “This is the first example of cellular origami,” Prakash said. “We’re thinking of calling it lacrygami.”Specifically, it is a subset of traditional origami known as “curved-crease origami.” It is all based on a structure of thin, helical microtubules – ribs that wrap inside the cell’s membrane. These microtubule ribs are encased in a delicate diaphanous membrane, defining the crease pattern of peaks in a series of mountain-and-valley folds.Prakash and Flaum used transmission electron microscopy and other state-of-the-art investigatory techniques to show there are actually 15 of these stiff, helical microtubule ribbons enshrouding&nbsp;L. olor’s cell membrane – a cytoskeleton. These tubules coil and uncoil, leading to long projection and retraction, nesting back into themselves like the bellows of a compressed helical accordion. The gossamer of membrane tucks away inside the cell in neat, well-defined pleats.“When you store pleats on the helical angle in this way, you can store an&nbsp;infinite amount of material,” Flaum explained. “Biology has figured this out.”<h2>Geometry is destiny</h2>The elegance is in the arithmetic. It is mathematically impossible for this structure to unfold in any other way – and, conversely, only one way it can retract. What is perhaps more striking to Prakash is the robustness of the architecture. In its lifetime,&nbsp;L. olor will perform this projection and retraction 50,000 times without flaw, he said: “L. olor is&nbsp;bound by its geometry to fold and unfold in this particular way.”The key is an under-studied mathematical phenomenon occurring at the precise point where the ribs twist and the folded membrane begins to unfurl. It is a&nbsp;singularity – a point where the structure is folded and unfolded at the same time. It is both and neither – singular.Grabbing a piece of paper, Prakash folds it into a cone shape and then pulls on one corner of the paper to demonstrate how this singularity (called d-cone) travels across the sheet in a neat line. And, by pushing back on the corner how the singularity travels back the exact same path to its original position.“It unfolds and folds at this singularity every time, acting as a controller. This is the first time a geometric controller of behavior has been described in a living cell.” Prakash explained.<h2>Recreational biology</h2>A constant theme running throughout the<a href="https://web.stanford.edu/group/prakash-lab/cgi-bin/labsite/publications/" data-extlink="" target="_blank">&nbsp;Prakash Lab’s</a> work is a profound sense of wonder and playfulness that results in the energetic curiosity necessary to pursue such an idea for such a long time. It is, to put it in Prakash’s terms, old-school science. He also calls it recreational biology.To demonstrate his inspiration, Prakash displayed a family tree of other single-celled organisms that he has chosen to study. True, none can do what&nbsp;L. olor can do, he said. But these intricate geometries come in thousands of forms. Beautiful? Certainly, but each is also hiding wonderful and unwritten rules under their sleeves.“We started with a puzzle,” Prakash explained with all the seriousness a scientist can muster. “Ellie and I asked a very simple question: Where does this material come from? And where does it go? As our playground, we chose Tree of Life. Seven years later, here we are.”As for practical applications, Prakash the engineer is already imagining a new era of deployable microscale “living machines” that could transform everything from space telescopes to miniature surgical robots in the operating room.

A side-by-side comparison of Lacrymaria olor, a remarkable ciliate with its “neck” extended and retracted. Researchers discovered origami-like folds make this morphing possible where microtubules define folding pleats. | Prakash Lab

Combining a deep curiosity and “recreational biology,” Stanford researchers have discovered how a simple cell produces remarkably complex behavior, all without a nervous system. It’s origami, they say.

The first example of cellular origami

The same geometric quirk that lets visitors murmur messages around the circular dome of the whispering gallery at St. Paul’s Cathedral in London or across St. Louis Union Station’s whispering arch also enables the construction of high-resolution optical sensors. Whispering-gallery-mode (WGM) resonators have been used for decades to detect chemical signatures, DNA strands and even single molecules.In the same way that the architecture of a whispering gallery bends and focuses sound waves, WGM microresonators confine and concentrate light in a tiny circular path. This enables WGM resonators to detect and quantify physical and biochemical characteristics, making them ideal for high-resolution sensing applications in fields such as biomedical diagnostics and environmental monitoring. However, the broad use of WGM resonators has been limited by their narrow dynamic range as well as their limited resolution and accuracy.&nbsp;In a recent study,&nbsp;<a href="https://engineering.wustl.edu/faculty/Lan-Yang.html" target="_blank">Lan Yang</a>, the Edwin H. &amp; Florence G. Skinner Professor, and Jie Liao, a postdoctoral research associate, both in the Preston M. Green Department of Electrical &amp; Systems Engineering in the McKelvey School of Engineering at Washington University in St. Louis, demonstrate a transformative approach to overcome these limitations:&nbsp;<a href="https://ieeexplore.ieee.org/abstract/document/10407034" target="_blank">optical WGM barcodes for multimode sensing</a>. Liao and Yang’s innovative technique allows simultaneous monitoring of multiple resonant modes within a single WGM resonator, considering distinctive responses from each mode, vastly expanding the range of measurements achievable.WGM sensing uses a specific wavelelength of light that can circulate around the perimeter of the microresonator millions of times. When the sensor encounters a molecule, the resonant frequency of the circulating light shifts. Researchers can then measure that shift to detect and identify the presence of specific molecules.“Multimode sensing allows us to pick up multiple resonance changes in wavelength, rather than just one,” Liao explained. “With multiple modes, we can expand optical WGM sensing to a greater range of wavelengths, achieve greater resolution and accuracy, and ultimately sense more particles.”Liao and Yang found the theoretical limit of WGM detection and used it to estimate the sensing capabilities of a multimode system. They compared conventional single-mode with multimode sensing and determined that while single-mode sensing is limited to very narrow range – about 20 picometers (pm), constrained by the laser hardware – the range for multimode sensing is potentially limitless using the same setup.“More resonance means more information,” Liao said. “We derived a theoretically infinite range, though we’re practically limited by the sensing apparatus. In this study, the experimental limit we found was about 350 times larger with the new method than the conventional method for WGM sensing.”Commercial applications of multimode WGM sensing could include biomedical, chemical and environmental uses, Yang said. In biomedical applications, for instance, researchers could detect subtle changes in molecular interactions with unprecedented sensitivity to improve disease diagnosis and drug discovery. In environmental monitoring, with the capability to detect minute changes in environmental parameters such as temperature and pressure, multimode sensing could enable early warning systems for natural disasters or facilitate monitoring pollution levels in air and water.This new technology also enables continuous monitoring of chemical reactions, as demonstrated in the recent experiments conducted by Yang’s group. This capability holds promise for real-time analysis and control of chemical processes, offering potential applications in fields such as pharmaceuticals, materials science, and the food industry.&nbsp;“WGM resonators’ ultrahigh sensitivity lets us detect single particles and ions, but the potential of this powerful technology has not been fully utilized because we can’t use this ultrasensitive sensor directly to measure a complete unknown,” Liao added. “Multimode sensing enables that look into the unknown. By expanding our dynamic range to look at millions of particles, we can take on more ambitious projects and solve real-world problems.”<hr>Liao J and Yang L. Multimode sensing by optical whispering-gallery-mode barcodes: A new route to expand dynamic range for high-resolution measurement.&nbsp;IEEE Transactions on Instrumentation and Measurement, online January 18, 2024. DOI: 10.1109/TIM.2024.3352712This work was supported by the National Institutes of Health (R21EB030845).

An innovative optical sensing technology, developed in Yang’s lab at the McKelvey School of Engineering, utilizes multimode resonance to boost sensing capabilities. By analyzing patterns in the resonance spectrum, the innovative barcode technique provides detailed information about the sensor's surroundings, offering enhanced dynamic range and accuracy in various sensing applications. (Credit: Yang Lab)

Lan Yang and Jie Liao’s optical barcodes for multimode sensing have potential applications in biomedical diagnostics, environmental monitoring, chemical sensing and more

Barcodes expand range of high-resolution sensor

Fat tissue holds the key to 3D printing layered living skin and potentially hair follicles, according to researchers who recently harnessed fat cells and supporting structures from clinically procured human tissue to precisely correct injuries in rats. The advancement could have implications for reconstructive facial surgery and even hair growth treatments for humans.&nbsp;The team’s findings published today (March 1) in&nbsp;<a href="https://doi.org/10.1016/j.bioactmat.2023.10.034" target="_blank">Bioactive Materials</a>. The U.S. Patent and Trademark Office granted the team a patent in February for the bioprinting technology it developed and used in this study.&nbsp;“Reconstructive surgery to correct trauma to the face or head from injury or disease is usually imperfect, resulting in scarring or permanent hair loss,” said Ibrahim T. Ozbolat, professor of engineering science and mechanics, of biomedical engineering and of neurosurgery at Penn State, who led the international collaboration that conducted the work. “With this work, we demonstrate bioprinted, full thickness skin with the potential to grow hair in rats. That’s a step closer to being able to achieve more natural-looking and aesthetically pleasing head and face reconstruction in humans.”While scientists have previously 3D bioprinted thin layers of skin, Ozbolat and his team are the first to intraoperatively print a full, living system of multiple skin layers, including the bottom-most layer or hypodermis. Intraoperatively refers to the ability to print the tissue during surgery, meaning the approach may be used to more immediately and seamlessly repair damaged skin, the researchers said. The top layer — the epidermis that serves as visible skin — forms with support from the middle layer on its own, so it doesn’t require printing. The hypodermis, made of connective tissue and fat, provides structure and support over the skull.“The hypodermis is directly involved in the process by which stem cells become fat,” Ozbolat said. “This process is critical to several vital processes, including wound-healing. It also has a role in hair follicle cycling, specifically in facilitating hair growth.”The researchers started with human adipose, or fat, tissue obtained from patients undergoing surgery at Penn State Health Milton S. Hershey Medical Center. Collaborator Dino J. Ravnic, associate professor of surgery in the Division of Plastic Surgery at Penn State College of Medicine, led his lab in obtaining the fat for extraction of the extracellular matrix — the network of molecules and proteins that provides structure and stability to the tissue — to make one component of the bioink.Ravnic’s team also obtained stem cells, which have the potential to mature into several different cell types if provided the correct environment, from the adipose tissue to make another bioink component. Each component was loaded into one of three compartments in the bioprinter. The third compartment was filled with a clotting solution that helps the other components properly bind onto the injured site.“The three compartments allow us to co-print the matrix-fibrinogen mixture along with the stem cells with precise control,” Ozbolat said. “We printed directly into the injury site with the target of forming the hypodermis, which helps with wound healing, hair follicle generation, temperature regulation and more.”They achieved both the hypodermis and dermis layers, with the epidermis forming within two weeks by itself.“We conducted three sets of studies in rats to better understand the role of the adipose matrix, and we found the co-delivery of the matrix and stem cells was crucial to hypodermal formation,” Ozbolat said. “It doesn’t work effectively with just the cells or just the matrix — it has to be at the same time.”They also found that the hypodermis contained downgrowths, the initial stage of early hair follicle formation. According to the researchers, while fat cells do not directly contribute to the cellular structure of hair follicles, they are involved in their regulation and maintenance.“In our experiments, the fat cells may have altered the extracellular matrix to be more supportive for downgrowth formation,” Ozbolat said. “We are working to advance this, to mature the hair follicles with controlled density, directionality and growth.”According to Ozbolat, the ability to precisely grow hair in injured or diseased sites of trauma can limit how natural reconstructive surgery may appear. He said that this work offers a “hopeful path forward,” especially in combination with other projects from his lab involving printing bone and investigating how to match pigmentation across a range of skin tones.“We believe this could be applied in dermatology, hair transplants, and plastic and reconstructive surgeries — it could result in a far more aesthetic outcome,” Ozbolat said.“With the fully automated bioprinting ability and compatible materials at the clinical grade, this technology may have a significant impact on the clinical translation of precisely reconstructed skin.”Ravnic and Ozbolat also are affiliated with the Huck Institutes of the Life Sciences and the Penn State Cancer Institute. Ozbolat has additional affiliations with the Penn State Materials Research Institute and the Department of Medical Oncology at Cukurova University in Turkey, where he is currently on sabbatical leave. Other contributors include Yogendra Pratap Singh, postdoctoral scholar, and Mecit Altan Alioglu, graduate student, both in the Penn State Department of Engineering Science and Mechanics; Youngnam Kang and Miji Yeo, both researchers, and Irem Deniz Derman, graduate student, in the Huck Institutes of the Life Sciences; Yang Wu, Harbin Institute of Technology in China; and Jasson Makkar and Ryan R. Driskell, College of Veterinary Medicine at Washington State University. Kang, Yeo, Singh, Alioglu and Derman also are affiliated with Penn State Department of Engineering Science and Mechanics.

Miji Yeo, a postdoctoral researcher at Penn State, checks the bioink cartridges on a 3D printer developed to intraoperatively print layers of skin. Credit: Michelle Bixby/Penn State. All Rights Reserved.

Bioengineered advancement may have implications for more natural-looking reconstructive surgery outcomes, according to international research team

3D-printed skin closes wounds and contains hair follicle precursors

<h2 id="isPasted">What is silver/silver chloride ink?</h2>‍Silver/silver chloride (Ag/AgCl) is a conductive ink typically used to print electrodes for biomedical applications. It’s a non-toxic, environmentally friendly ink with stable electrochemical potential used to create disposable on-skin medical electrodes for biosensors, like "ECG, EEG and TENS electrodes; defibrillator pads; transdermal drug delivery; biomedical sensors and reference electrodes," according to <a href="https://www.creativematerials.com/products/ag-agcl-inks/" target="_blank">Creative Materials</a>.&nbsp;‍<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1709524616616-63d022dacfb6e86a1a3cf1c4_ffhgM2WgWmVRDuIv4GtMPtOgJnNsHrpU0DlhQb2hw9DhzCZ4C7IujXkmI6-Wb1oQkcFbDkFukxQI-6qOCSdGzc-RG3ihBfYeMomcrtZXFV6dX66qBWO6I56fjNV7IngcIVg4ZVpc3em72_ZUQ7XEEeOsDnoXYJ3UkXIu4GSpT1uTJ1njEsNQKtcxJaKNC.png" style="width: 100%px;" class="fr-fic fr-dib">Source: Henkel<h3 id="isPasted">Features:</h3><ul><li>Silver-to-silver chloride ratios can be adjusted and blended to achieve different resistance values and sensitivity levels.&nbsp;</li><li>The ink has a smooth surface finish with excellent adhesion and crease resistance when printed onto polyester and plastic substrates.&nbsp;</li><li>Silver/silver chloride is compatible with screen printing and direct-ink-writing printing technology.&nbsp;</li></ul><h2>Smart health patches</h2>‍Used in both healthcare and athletics applications, smart health patches deliver new capabilities in monitoring. These devices can continuously measure heart rate, brain activity, movement, and other body functions. <a href="https://www.quad-ind.com/smart-health-patches-to-run-smart/" target="_blank">Quad Industries’ Smart Health Patch</a>, designed to optimize training for ultra-runners, is made using Henkel’s silver/silver chloride ink.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1709524652661-63d022daa5cbee3ab018e3e7_8VgrqoubKIfwaL1zITpxMMjBjwZ0pwQdx2p_UCyq48yZIDh9jqqb281s3xO3BjQ7xTJO1oM0xUcUoKoQ6506xXmB2AnVlUENl_QzrSiBiDSWsE25qMLNrOtCmqt1c8hxKm-xZMRmZoxMabvNRQA6Udn9Q6RByf0cqbC_Dy22HfbQWYy4S7Tu8SvzcJjw9.png" style="width: 100%px;" class="fr-fic fr-dib">Source: Quad Industries<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1709524667591-63d022dac9c95f5daebb1936_7x7-GMmj24mLom3wqW-nHmMi9PeRUDPwS6Pv5tYsxw_QONplpV8Uyxc6qzd6FJCo3t4G_uNybUwFGiJohdDlYNlrqbXxN0Dv3g1kujpKAT8hPn5BLnvSYClXC0DZIMi8kvIL44HJyqEZwq3CgivP2w_SNr8UElf52dxJI3B_k1N1qiwnP6yNkXgmyRzOe.png" style="width: 100%px;" class="fr-fic fr-dib"><figure data-rt-type="image" data-rt-align="center" id="isPasted"><figcaption>Source: Quad Industries‍</figcaption></figure>‍Silver/silver chloride ink is also used to print glucose sensors for continuous glucose monitoring (CGM) patches like Freestyle Libre.CGM patches are being widely adopted for diabetes management. Rather than pricking a finger several times a day to monitor glucose levels, the CGM continuously measures glucose in the blood and interfaces with a reader device or smartphone app. This allows patients to monitor glucose levels throughout the day and refine the timing for their insulin injections.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1709524688181-63d022da3ae9a36f914066d5_hHSjbJgZWS36H1qokZ_5LN2coCJiIs7H9b7Uw6TUm0o7Qbss4LCqngtZB53W-wdG_sMiMR7KnUMKSRcuX3OhSHY_ngYl7SoPJEe1ZVD_LTrvMQfALXzmxpZAVSwQMxAkHLrVb_SZ0MxJqfYS9fmmN_cH8CSOwUOq1YLmYLEZqfyrDEwgtp1lhSBGSFLoV.png" style="width: 100%px;" class="fr-fic fr-dib">Source: Healthline<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1709524702228-63d022da3916c36e5646942d_QdXGhsRpN4wtDyT6VosSkgxf0n4hxX7QICaxkDGbyBOM1Ar0t7ehDpr8ZQoIHzbhKxWRzY8_0G1bBz20I3Yi61Pf0pI0vCZ-6Bd6a7TGwEZp6waSXE0_Ascb-h8PVZQsQcwqcIt5-SUFVGauo6chHPNjqTfZa3hUNWCJfkaXF0WyMdRWn0TQdMiYLySC.jpeg" style="width: 100%px;" class="fr-fic fr-dib">Source: Advanced Technologies and Polymer Materials for Surgical Sutures<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1709524715190-63d022dad7285c542dc110f7_YSW1DtYARgBxTI1OcJYkuL_bHjR4eAI01NARpWowdleL1PdML6EBfQ_ksZ3d9jS4o9G6m6beeDeroNPsSs1OxRiOhx7wZA7-ws935lrFJZpgSVoHFMf49r1TYDTgE-eP-sOOrhR3C15nlwi19GzLEiqP-VQNR-vhQo7fOW3MlwK5SiBN7Uh-ltI3qhHSP.png" style="width: 100%px;" class="fr-fic fr-dib">Source: HenkelIn recent years, CGMs also have become a tool for athletic performance. Endurance athletes use CGMs to monitor for dips in glucose during training, and then methodically dial in their fuel strategy and nutrition plan accordingly. The <a href="https://www.supersapiens.com/" target="_blank">Supersapiens</a> glucose monitoring system is being leveraged by athletes like Crossfit Games champion Samantha Briggs, olympic triathlon gold medalist Kristian Blummenfelt, and endurance obstacle course world champion Ryan Atkins.&nbsp;<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1709524734463-63d022dabc5f8813d838b2d8_x7tSiD3dwvioNowEvZUasv-THGBtHupPy1ikaI29n8xyFH_LLcNtG0P3YC-ZncS2A82C9caDVwLeK1aHPlWYoN5ex_AI4YwzcVdOPMuK5d9AG7Os9XvLz1v68Xk56Uu_Q_DKjbceQ84tf8ZoTsFuLDn4GvyU6fWrkS92eL7nrIRSUA7ehMEgPfYecPW2F.png" style="width: 768px;" class="fr-fic fr-dib">Source: SupersapiensSilver/silver chloride ink can also be paired with TPU used to print stretchable interconnections for constructing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163896/" target="_blank">medical sensor textiles</a> and <a href="https://journals.sagepub.com/doi/abs/10.1177/00405175211005039" target="_blank">smart textile garments</a>. Commercialization has been limited due to lack of cost-effective, standard fabrication processes that can be applied to a large variety of fabrics, but companies like <a href="https://softmatter.io/" target="_blank">Softmatter</a> and <a href="https://www.memtronik.com/printed-electronics/smart-clothing/" target="_blank">Memtronik</a> now offer customized smart-garment design and fabrication.<hr><h2>I want this ink. Where do I start?</h2><h4>‍Henkel Adhesive Technologies</h4>If you work in the engineering world, you’re probably familiar with Loctite, a line of products by Henkel Adhesive Technologies. Loctite EDAG 7019 E&amp;C is a silver/silver chloride conductive ink, formulated to provide excellent adhesion to the wide variety of substrates used in the manufacture of electrically conductive medical devices.&nbsp;Read the datasheet here: <a href="https://tds.henkel.com/tds5/Studio/ShowPDF/?pid=EDAG%207019%20EC&format=MTR&subformat=HYS&language=EN&plant=WERCS&authorization=2" target="_blank">LOCTITE EDAG 7019 E&amp;C Technical Data Sheet </a>Henkel also sells a&nbsp;<a href="https://print-your-electronics-with-loctite.com/LOCTITE-SENSOR-DEMONSTRATOR" target="_blank">Loctite sensor demonstrator kit</a> with twelve dry adhesive electrodes for medical research and technical material validation. Henkel Adhesive Technologies have developed a wide portfolio of innovative solutions in adhesives, sealants, inks, and functional coatings.&nbsp;<h4>Dupont</h4>‍Another option is Dupont 5874 silver/silver chloride, which is designed for screen printing on polyester, and is suitable for a wide variety of biomedical applications. Dupont is an industry leader in materials development, combining scientific and applications development expertise to accelerate innovation. Read the datasheet here: <a href="https://www.dupont.com/content/dam/dupont/amer/us/en/mobility/public/documents/en/EI-10086-DuPont-5874-Ag_AgCI-Composition-Data-Sheet.pdf" target="_blank" data-lf-fd-inspected-kn9eq4roawkarlvp="true">Dupont 5874 silver/silver chloride composition for screen printing</a><h4>Kayaku Advanced Materials‍</h4>Kayaku Advanced Materials also offers a silver/silver chloride conductive ink, designed for screen printing medical EEG and EKG sensors. Kayaku develops and manufactures innovative specialty materials to push the latest innovation trends. Read the datasheet here: <a href="https://kayakuam.com/wp-content/uploads/2020/03/agcl-675-silver-chloride-ink.pdf" target="_blank" data-lf-fd-inspected-kn9eq4roawkarlvp="true">AGCL-675 SILVER/SILVER CHLORIDE INK&nbsp;</a>

‍Silver/silver chloride (Ag/AgCl) is a conductive ink typically used to print electrodes for biomedical applications.

Materials Feature: Silver or Silver Chloride Ink

In this episode, we talk about a new AI designed catheter that is 100x safer than and how it came to be after a passive conversation about fun facts between two researchers.

Podcast: AI Makes Catheters 100 Times Safer

“Soft robots,” medical devices and implants, and next-generation drug delivery methods could soon be guided with magnetism—thanks to a metal-free magnetic gel developed by researchers at the University of Michigan and the Max Planck Institute for Intelligent Systems in Stuttgart, Germany.The material is the first in which carbon-based, magnetic molecules are chemically bonded to the molecular network of a gel, creating a flexible, long-lived magnet for soft robotics. The study describing the material was published today in the journal Matter.Creating robots from flexible materials allows them to <a href="https://ieeexplore.ieee.org/document/7527653" target="_blank" rel="noreferrer noopener">contort</a> in unique ways, <a href="https://www.pnas.org/doi/10.1073/pnas.2209819119" target="_blank" rel="noreferrer noopener">handle delicate objects</a> and explore places that other robots cannot. More rigid robots would be crushed by the<a href="https://www.nature.com/articles/s41586-020-03153-z" target="_blank" rel="noreferrer noopener">&nbsp;deep ocean’s pressure</a> or could damage sensitive tissues in <a href="https://www.science.org/doi/full/10.1126/scirobotics.abc8191?casa_token=hqd5r3mI-VQAAAAA%3AJVE7YGtecWNWrACNynbQVLZfQCkJE6ngbzcmRnFo7u2Lb2K2oD6suzJvchvjpYa0zj9w4VBjykjmwQ" target="_blank" rel="noreferrer noopener">the human body</a>, for example.“If you make robots soft, you need to come up with new ways to give them power and make them move so that they can do work,” said <a href="https://mse.engin.umich.edu/people/abdon" target="_blank" rel="noreferrer noopener">Abdon Pena-Francesch</a>, assistant professor of materials science and engineering affiliated with the Robotics Institute at the University of Michigan and a corresponding author of the study.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1706103853343-Precursor-material-1.jpg" style="width: 766px;" class="fr-fic fr-dib">Pena-Francesch holds the soft gel before it is treated with chemicals that give the material its magnetic properties. The colorless precursor can be molded into a variety of shapes—such as capsules that could one day be ingested to deliver medicine. Photo credit: Brenda Ahearn, Michigan Engineering.Today’s prototypes typically move with hydraulics or mechanical wires, which require the robot to be tethered to a power source or controller, also limiting where they can go. Magnets could unleash these robots, enabling them to be moved by magnetic fields.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1706103920253-TEMPO_structure.png" style="width: 740px;" class="fr-fic fr-dib">The chemical structure of the organic magnet. Brown lines and black nodes show the general layout of the “cross-linking molecules” that serve as the frame for the gel’s molecular structure and a cage for the TEMPO molecules (shown in red). The TEMPO molecules are bonded directly to the gel structure. Free electrons on the TEMPO oxygen atoms (shown as dots) give the material its magnetic properties. Image credit: Abdon Pena-Francesch, BioInspired Materials Lab, University of Michigan.Conventional, metallic magnets introduce their own complications, however. They could reduce the flexibility of soft robots and be too <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jab.770060110" target="_blank" rel="noreferrer noopener">toxic</a> for some medical applications.The new gel could be a nontoxic alternative for medical operations, and further modifications to the magnet’s chemical structure could help it degrade in the environment and human body. Such biodegradable magnets could be used in capsules that are guided to targeted locations of the body to release medicine.“If these materials can safely degrade in your body, you don’t have to retrieve them with another surgery later,” Pena-Francesch said. “This is still pretty exploratory, but these materials could enable newer, cheaper medical operations some day.”The team’s gel consists solely of carbon-based molecules. The key ingredient is TEMPO, a molecule with a “free” electron that is not paired up with another electron inside an atomic bond. The spin of every unpaired TEMPO electron in the gel aligns under a magnetic field, which attracts the gel to other magnetic materials.<img src="https://s3-us-west-1.amazonaws.com/wevolver-project-images/froala%2F1706103947442-BlockM.jpg" style="width: 594px;" class="fr-fic fr-dib">The magnetic gel can be carved and molded into a variety of shapes, including the University of Michigan block M. Photo credit: Abdon Pena-Francesch, BioInspired Materials Lab, University of Michigan.Additional “cross-linking molecules” in the gel act like a frame that connects the TEMPO molecules to a solid network structure while forming a protective cage around the TEMPO electrons. That cage prevents the unpaired electrons from forming bonds, which would remove the gel’s magnetic properties.“Earlier studies soaked these small, magnetic molecules into a gel, but they could leak out of the gel,” said Zane Zhang, a doctoral student in materials science and engineering and co-author of the study. “By integrating the magnetic molecules into the cross-linked gel network, they are fixed inside.”Locking the TEMPO molecules inside the material ensures that the gel does not leak potentially harmful TEMPO molecules into the body and allows the material to retain its magnetic properties for more than a year.While weaker than metallic magnets, the TEMPO magnets are strong enough to be pulled and bent with another magnet. Their weaker magnetism also has some upsides—TEMPO magnets can be photographed by an MRI, unlike stronger magnets that can&nbsp;<a href="https://med.stanford.edu/bmrgroup/Research/mri-near-metal.html" target="_blank" rel="noreferrer noopener">distort MRI images</a> to the point of uselessness.“Medical devices using our magnets could be used to deliver drugs to target locations and measure tissue adhesion and mechanics in the GI tract under MRI imaging,” said Metin Sitti, former director of the Physical Intelligence Department at Max Planck Institute for Intelligent Systems and a corresponding author of the study.<iframe width="640" height="360" src="https://www.youtube.com/embed/NTAWzVN5pNg?&amp;wmode=opaque&amp;rel=0&amp;enablejsapi=1&amp;origin=https://www.wevolver.com" frameborder="0" allowfullscreen="" class="fr-draggable" data-gtm-yt-inspected-9="true" data-lf-form-tracking-inspected-kn9eq4roawkarlvp="true" data-lf-yt-playback-inspected-kn9eq4roawkarlvp="true" data-lf-vimeo-playback-inspected-kn9eq4roawkarlvp="true"></iframe>Designing Non-Metallic Squishy Magnets to Power Soft Robots

Strong enough to move soft robots and medical capsules, weak enough to not ruin MRI images

Squishy, metal-free magnets to power robots and guide medical implants

MIT engineers have developed a robotic replica of the heart’s right ventricle, which mimics the beating and blood-pumping action of live hearts.The robo-ventricle combines real heart tissue with synthetic, balloon-like artificial muscles that enable scientists to control the ventricle’s contractions while observing how its natural valves and other intricate structures function.The artificial ventricle can be tuned to mimic healthy and diseased states. The team manipulated the model to simulate conditions of right ventricular dysfunction, including pulmonary hypertension and myocardial infarction. They also used the model to test cardiac devices. For instance, the team implanted a mechanical valve to repair a natural malfunctioning valve, then observed how the ventricle’s pumping changed in response.They say the new robotic right ventricle, or RRV, can be used as a realistic platform to study right ventricle disorders and test devices and therapies aimed at treating those disorders.“The right ventricle is particularly susceptible to dysfunction in intensive care unit settings, especially in patients on mechanical ventilation,” says Manisha Singh, a postdoc at MIT’s Institute for Medical Engineering and Science (IMES). “The RRV simulator can be used in the future to study the effects of mechanical ventilation on the right ventricle and to develop strategies to prevent right heart failure in these vulnerable patients.”Singh and her colleagues report details of the new design in an open-access&nbsp;<a href="https://www.nature.com/articles/s44161-023-00387-8" target="_blank">paper appearing today in&nbsp;Nature Cardiovascular Research</a>. Her co-authors include Associate Professor Ellen Roche, who is a core member of IMES and the associate head for research in the Department of Mechanical Engineering at MIT; along with Jean Bonnemain, Caglar Ozturk, Clara Park, Diego Quevedo-Moreno, Meagan Rowlett, and Yiling Fan of MIT; Brian Ayers of Massachusetts General Hospital; Christopher Nguyen of Cleveland Clinic; and Mossab Saeed of Boston Children’s Hospital.<h2>A ballet of beats</h2>The right ventricle is one of the heart’s four chambers, along with the left ventricle and the left and right atria. Of the four chambers, the left ventricle is the heavy lifter, as its thick, cone-shaped musculature is built for pumping blood through the entire body. The right ventricle, Roche says, is a “ballerina” in comparison, as it handles a lighter though no-less-crucial load.“The right ventricle pumps deoxygenated blood to the lungs, so it doesn’t have to pump as hard,” Roche notes. “It’s a thinner muscle, with more complex architecture and motion.”This anatomical complexity has made it difficult for clinicians to accurately observe and assess right ventricle function in patients with heart disease.“Conventional tools often fail to capture the intricate mechanics and dynamics of the right ventricle, leading to potential misdiagnoses and inadequate treatment strategies,” Singh says.To improve understanding of the lesser-known chamber and speed the development of cardiac devices to treat its dysfunction, the team designed a realistic, functional model of the right ventricle that both captures its anatomical intricacies and reproduces its pumping function. &nbsp;The model includes real heart tissue, which the team chose to incorporate because it retains natural structures that are too complex to reproduce synthetically.“There are thin, tiny chordae and valve leaflets with different material properties that are all moving in concert with the ventricle’s muscle. Trying to cast or print these very delicate structures is quite challenging,” Roche explains.<h2>A heart’s shelf-life</h2>In the new study, the team reports explanting a pig’s right ventricle, which they treated to carefully preserve its internal structures. They then fit a silicone wrapping around it, which acted as a soft, synthetic myocardium, or muscular lining. Within this lining, the team embedded several long, balloon-like tubes, which encircled the real heart tissue, in positions that the team determined through computational modeling to be optimal for reproducing the ventricle’s contractions. The researchers connected each tube to a control system, which they then set to inflate and deflate each tube at rates that mimicked the heart’s real rhythm and motion.To test its pumping ability, the team infused the model with a liquid similar in viscosity to blood. This particular liquid was also transparent, allowing the engineers to observe with an internal camera how internal valves and structures responded as the ventricle pumped liquid through.They found that the artificial ventricle’s pumping power and the function of its internal structures were similar to what they previously observed in live, healthy animals, demonstrating that the model can realistically simulate the right ventricle’s action and anatomy. The researchers could also tune the frequency and power of the pumping tubes to mimic various cardiac conditions, such as irregular heartbeats, muscle weakening, and hypertension.“We’re reanimating the heart, in some sense, and in a way that we can study and potentially treat its dysfunction,” Roche says.To show that the artificial ventricle can be used to test cardiac devices, the team surgically implanted ring-like medical devices of various sizes to repair the chamber’s tricuspid valve — a leafy, one-way valve that lets blood into the right ventricle. When this valve is leaky, or physically compromised, it can cause right heart failure or atrial fibrillation, and leads to symptoms such as reduced exercise capacity, swelling of the legs and abdomen, and liver enlargement.The researchers surgically manipulated the robo-ventricle’s valve to simulate this condition, then either replaced it by implanting a mechanical valve or repaired it using ring-like devices of different sizes. They observed which device improved the ventricle’s fluid flow as it continued to pump.“With its ability to accurately replicate tricuspid valve dysfunction, the RRV serves as an ideal training ground for surgeons and interventional cardiologists,” Singh says. “They can practice new surgical techniques for repairing or replacing the tricuspid valve on our model before performing them on actual patients.”Currently, the RRV can simulate realistic function over a few months. The team is working to extend that performance and enable the model to run continuously for longer stretches. They are also working with designers of implantable devices to test their prototypes on the artificial ventricle and possibly speed their path to patients. And looking far in the future, Roche plans to pair the RRV with a similar artificial, functional model of the left ventricle, which the group is currently fine-tuning.“We envision pairing this with the left ventricle to make a fully tunable, artificial heart, that could potentially function in people,” Roche says. “We’re quite a while off, but that’s the overarching vision.”This research was supported, in part, by the National Science Foundation.

A new bio-robotic model developed by MIT engineers simulates the function of the heart’s lesser-known right ventricle (illustrated here in cross-section, as seen from a front view, on the left). Soft, balloon-like “muscles” (in blue) wrap around and contract the ventricle, mimicking its real pumping action. The model could help to test new implants and devices to treat a range of cardiac disorders. Credit: Courtesy of the researchers

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