Siddharth Krishnan

All Publications

• Wireless battery-free oxygenation devices enable extended immunosuppression-free islet transplantation in minimally invasive sites DEVICE Krishnan, S. R., Bochenek, M. A., Pan, J., Pendyala, S., Chan, S., Liu, C., Prokop, E., Hogrebe, N., Rios, P. D., Lopez, D., Potdar, S., Gumustop, D., Her, B. S., O'Keeffe, L., Millman, J. R., Oberholzer, J., Langer, R., Anderson, D. G. 2026; 4 (5)

  Abstract

  Here, we develop a next-generation wireless, battery-free oxygen generating O2-Macrodevice and wearable power transfer platform that can enable long-term immune protection and subcutaneous function of therapeutic cells. We demonstrate this device supports xenogeneic islet transplantation in C57BL/6J mice evidenced by 90-day diabetes reversal and glucose responsiveness in vivo. We also show partial glycemic control via high-density (>8,000 islets/cm2) human stem-cell derived islets (SC-islets) without immune-suppression in subcutaneous sites for 90 days. Additionally, we confirmed the device supports allogenic islet cell survival and 90-day diabetic reversal in rats. Finally, we demonstrate 1-month islet survival in a nonhuman primate without the need for immune suppression in the subcutaneous space. Collectively, these results indicate the device supports cell survival and function across multiple transplant models in three species without the need for any immunosuppression or external user intervention. These results represent an important set of advances towards immunosuppression free, minimally invasive islet transplantation.

  View details for DOI 10.1016/j.device.2026.101084

  View details for Web of Science ID 001777223900001

  View details for PubMedID 42182975

  View details for PubMedCentralID PMC13196877

• Emergency delivery of particulate drugs by active ejection using in vivo wireless devices. Nature biomedical engineering Krishnan, S. R., O'Keeffe, L., Rudra, A., Gumustop, D., Khatib, N., Liu, C., Yang, J., Wang, A., Bochenek, M. A., Lu, Y. C., Bose, S., Reed, K., Langer, R., Anderson, D. G. 2026; 10 (1): 144-160

  Abstract

  Rapidly administered emergency drug therapy represents life-saving treatment for a range of acute conditions including hypoglycaemia, anaphylaxis and cardiac arrest. Devices that automate emergency delivery, such as pumps and automated injectors, are limited by the low stability of liquid formulations. In contrast, dry particulate formulations of these drugs are stable but are incompatible with drug pumps and require reconstitution before administration. Here we develop a miniaturized (<3 cm3), lightweight (<2 g), minimally invasive, fully wireless emergency rescue device for the storage and active burst-release of indefinitely stable particulate forms of peptide and hormone drugs into subcutaneous sites for direct reconstitution in interstitial biofluids and rapid (<5 min) therapeutic effect. Importantly, the device delivers drug across fibrotic tissue, which commonly accumulates following in vivo implantation, thereby accelerating systemic delivery. Fully wireless delivery of dry particulate glucagon in vivo is demonstrated, providing emergency hypoglycaemic rescue in diabetic mice. In addition, triggered delivery of epinephrine is demonstrated in vivo. This work provides a platform for the long-term in vivo closed-loop delivery of emergency rescue drugs.

  View details for DOI 10.1038/s41551-025-01436-2

  View details for PubMedID 40634646

  View details for PubMedCentralID PMC13120775

• Materials approaches for next-generation encapsulated cell therapies. MRS communications Krishnan, S. R., Langer, R., Anderson, D. G. 2025; 15 (1): 21-33

  Abstract

  Transplanted cells can act as living drug factories capable of secreting therapeutic proteins in vivo, with applications in the treatment of Type 1 diabetes (T1D), blood borne disease, vision disorders, and degenerative neural disease, potentially representing functional cures for chronic conditions. However, attack from the host immune system represents a major challenge, requiring chronic immunosuppression to enable long-lived cell transplantation in vivo. Encapsulating cells in engineered biomaterials capable of excluding components of the host immune system while allowing for the transport of therapeutic proteins, oxygen, nutrients, metabolites, and waste products represents a potential solution. However, the foreign-body response can lead to isolation from native vasculature and hypoxia leading to cell death. In this prospective article, we highlight materials-based solutions to three important challenges in the field: (i) improving biocompatibility and reducing fibrosis; (ii) enhancing transport of secreted protein drugs and key nutrients and oxygen via engineered, semipermeable membranes; and (iii) improving oxygenation. These efforts draw on several disciplines in materials' research, including polymer science, surfaces, membranes, biomaterials' microfabrication, and flexible electronics. If successful, these efforts could lead to new therapies for chronic disease and are a rich space for both fundamental materials' discovery and applied translational science.

  View details for DOI 10.1557/s43579-024-00678-6

  View details for PubMedID 39958992

  View details for PubMedCentralID PMC11825545

• A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo. Proceedings of the National Academy of Sciences of the United States of America Krishnan, S. R., Liu, C., Bochenek, M. A., Bose, S., Khatib, N., Walters, B., O'Keeffe, L., Facklam, A., Langer, R., Anderson, D. G. 2023; 120 (40): e2311707120

  Abstract

  The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O2 requirements. Here, we combine bioelectronics with encapsulated cell therapies to develop the first wireless, battery-free oxygen-generating immune-isolating device (O2-Macrodevice) for the oxygenation and immune isolation of cells in vivo. The system relies on electrochemical water splitting based on a water-vapor reactant feed, sustained by wireless power harvesting based on a flexible resonant inductive coupling circuit. As such, the device does not require pumping, refilling, or ports for recharging and does not generate potentially toxic side products. Through systematic in vitro studies with primary cell lines and cell lines engineered to secrete protein, we demonstrate device performance in preventing hypoxia in ambient oxygen concentrations as low as 0.5%. Importantly, this device has shown the potential to enable subcutaneous (SC) survival of encapsulated islet cells, in vivo in awake, freely moving, immune-competent animals. Islet transplantation in Type I Diabetes represents an important application space, and 1-mo studies in immune-competent animals with SC implants show that the O2-Macrodevice allows for survival and function of islets at high densities (~1,000 islets/cm2) in vivo without immune suppression and induces normoglycemia in diabetic animals.

  View details for DOI 10.1073/pnas.2311707120

  View details for PubMedID 37738292

  View details for PubMedCentralID PMC10556620

• Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus NPJ DIGITAL MEDICINE Krishnan, S. R., Arafa, H. M., Kwon, K., Deng, Y., Su, C., Reeder, J. T., Freudman, J., Stankiewicz, I., Chen, H., Loza, R., Mims, M., Mims, M., Lee, K., Abecassis, Z., Banks, A., Ostojich, D., Patel, M., Wang, H., Borekci, K., Rosenow, J., Tate, M., Huang, Y., Alden, T., Potts, M. B., Ayer, A. B., Rogers, J. A. 2020; 3 (1): 29

  Abstract

  Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.

  View details for DOI 10.1038/s41746-020-0239-1

  View details for Web of Science ID 000519040400002

  View details for PubMedID 32195364

  View details for PubMedCentralID PMC7060317

• Epidermal electronics for noninvasive, wireless, quantitative assessment of ventricular shunt function in patients with hydrocephalus SCIENCE TRANSLATIONAL MEDICINE Krishnan, S. R., Ray, T. R., Ayer, A. B., Ma, Y., Gutruf, P., Lee, K., Lee, J., Wei, C., Feng, X., Ng, B., Abecassis, Z. A., Murthy, N., Stankiewicz, I., Freudman, J., Stillman, J., Kim, N., Young, G., Goudeseune, C., Ciraldo, J., Tate, M., Huang, Y., Potts, M., Rogers, J. A. 2018; 10 (465)

  Abstract

  Hydrocephalus is a common and costly neurological condition caused by the overproduction and/or impaired resorption of cerebrospinal fluid (CSF). The current standard of care, ventricular catheters (shunts), is prone to failure, which can result in nonspecific symptoms such as headaches, dizziness, and nausea. Current diagnostic tools for shunt failure such as computed tomography (CT), magnetic resonance imaging (MRI), radionuclide shunt patency studies (RSPSs), and ice pack-mediated thermodilution have disadvantages including high cost, poor accuracy, inconvenience, and safety concerns. Here, we developed and tested a noninvasive, skin-mounted, wearable measurement platform that incorporates arrays of thermal sensors and actuators for precise, continuous, or intermittent measurements of flow through subdermal shunts, without the drawbacks of other methods. Systematic theoretical and experimental benchtop studies demonstrate high performance across a range of practical operating conditions. Advanced electronics designs serve as the basis of a wireless embodiment for continuous monitoring based on rechargeable batteries and data transmission using Bluetooth protocols. Clinical studies involving five patients validate the sensor's ability to detect the presence of CSF flow (P = 0.012) and further distinguish between baseline flow, diminished flow, and distal shunt failure. Last, we demonstrate processing algorithms to translate measured data into quantitative flow rate. The sensor designs, fabrication schemes, wireless architectures, and patient trials reported here represent an advance in hydrocephalus diagnostics with ability to visualize flow in a simple, user-friendly mode, accessible to the physician and patient alike.

  View details for DOI 10.1126/scitranslmed.aat8437

  View details for Web of Science ID 000448834800004

  View details for PubMedID 30381410

• The road ahead for applications of mechanics in drug delivery br MECHANICS RESEARCH COMMUNICATIONS Sarmadi, M., Krishnan, S. R., Ramadi, K. B., Langer, R. 2022; 125

  View details for DOI 10.1016/j.mechrescom.2022.103956

  View details for Web of Science ID 000860346400006

• An on-skin platform for wireless monitoring of flow rate, cumulative loss and temperature of sweat in real time NATURE ELECTRONICS Kwon, K., Kim, J., Deng, Y., Krishnan, S. R., Choi, J., Jang, H., Lee, K., Su, C., Yoo, I., Wu, Y., Lipschultz, L., Kim, J., Chung, T. S., Wu, D., Park, Y., Kim, T., Ghaffari, R., Lee, S., Huang, Y., Rogers, J. A. 2021; 4 (4): 302-312

  View details for DOI 10.1038/s41928-021-00556-2

  View details for Web of Science ID 000634634500001

• Battery-free, fully implantable optofluidic cuff system for wireless optogenetic and pharmacological neuromodulation of peripheral nerves. Science advances Zhang, Y., Mickle, A. D., Gutruf, P., McIlvried, L. A., Guo, H., Wu, Y., Golden, J. P., Xue, Y., Grajales-Reyes, J. G., Wang, X., Krishnan, S., Xie, Y., Peng, D., Su, C. J., Zhang, F., Reeder, J. T., Vogt, S. K., Huang, Y., Rogers, J. A., Gereau, R. W. 2019; 5 (7): eaaw5296

  Abstract

  Studies of the peripheral nervous system rely on controlled manipulation of neuronal function with pharmacologic and/or optogenetic techniques. Traditional hardware for these purposes can cause notable damage to fragile nerve tissues, create irritation at the biotic/abiotic interface, and alter the natural behaviors of animals. Here, we present a wireless, battery-free device that integrates a microscale inorganic light-emitting diode and an ultralow-power microfluidic system with an electrochemical pumping mechanism in a soft platform that can be mounted onto target peripheral nerves for programmed delivery of light and/or pharmacological agents in freely moving animals. Biocompliant designs lead to minimal effects on overall nerve health and function, even with chronic use in vivo. The small size and light weight construction allow for deployment as fully implantable devices in mice. These features create opportunities for studies of the peripheral nervous system outside of the scope of those possible with existing technologies.

  View details for DOI 10.1126/sciadv.aaw5296

  View details for PubMedID 31281895

  View details for PubMedCentralID PMC6611690

• Fully implantable optoelectronic systems for battery-free, multimodal operation in neuroscience research NATURE ELECTRONICS Gutruf, P., Krishnamurthi, V., Vazquez-Guardado, A., Xie, Z., Banks, A., Su, C., Xu, Y., Haney, C. R., Waters, E. A., Kandela, I., Krishnan, S. R., Ray, T., Leshock, J. P., Huang, Y., Chanda, D., Rogers, J. A. 2018; 1 (12): 652-660

  View details for DOI 10.1038/s41928-018-0175-0

  View details for Web of Science ID 000455967800014

• Wireless, Battery-Free Epidermal Electronics for Continuous, Quantitative, Multimodal Thermal Characterization of Skin. Small (Weinheim an der Bergstrasse, Germany) Krishnan, S. R., Su, C. J., Xie, Z., Patel, M., Madhvapathy, S. R., Xu, Y., Freudman, J., Ng, B., Heo, S. Y., Wang, H., Ray, T. R., Leshock, J., Stankiewicz, I., Feng, X., Huang, Y., Gutruf, P., Rogers, J. A. 2018; 14 (47): e1803192

  Abstract

  Precise, quantitative measurements of the thermal properties of human skin can yield insights into thermoregulatory function, hydration, blood perfusion, wound healing, and other parameters of clinical interest. The need for wired power supply systems and data communication hardware limits, however, practical applicability of existing devices designed for measurements of this type. Here, a set of advanced materials, mechanics designs, integration schemes, and wireless circuits is reported as the basis for wireless, battery-free sensors that softly interface to the skin to enable precise measurements of its temperature and thermal transport properties. Calibration processes connect these parameters to the hydration state of the skin, the dynamics of near-surface flow through blood vessels and implanted catheters, and to recovery processes following trauma. Systematic engineering studies yield quantitative metrics in precision and reliability in real-world conditions. Evaluations on five human subjects demonstrate the capabilities in measurements of skin hydration and injury, including examples of continuous wear and monitoring over a period of 1 week, without disrupting natural daily activities.

  View details for DOI 10.1002/smll.201803192

  View details for PubMedID 30369049

• Epidermal Electronic Systems for Measuring the Thermal Properties of Human Skin at Depths of up to Several Millimeters ADVANCED FUNCTIONAL MATERIALS Madhvapathy, S. R., Ma, Y., Patel, M., Krishnan, S., Wei, C., Li, Y., Xu, S., Feng, X., Huang, Y., Rogers, J. A. 2018; 28 (34)

  View details for DOI 10.1002/adfm.201802083

  View details for Web of Science ID 000442205200011

• Multimodal epidermal devices for hydration monitoring MICROSYSTEMS & NANOENGINEERING Krishnan, S., Shi, Y., Webb, R., Ma, Y., Bastien, P., Crawford, K. E., Wang, A., Feng, X., Manco, M., Kurniawan, J., Tir, E., Huang, Y., Balooch, G., Pielak, R. M., Rogers, J. A. 2017; 3: 17014

  Abstract

  Precise, quantitative in vivo monitoring of hydration levels in the near surface regions of the skin can be useful in preventing skin-based pathologies, and regulating external appearance. Here we introduce multimodal sensors with important capabilities in this context, rendered in soft, ultrathin, 'skin-like' formats with numerous advantages over alternative technologies, including the ability to establish intimate, conformal contact without applied pressure, and to provide spatiotemporally resolved data on both electrical and thermal transport properties from sensitive regions of the skin. Systematic in vitro studies and computational models establish the underlying measurement principles and associated approaches for determination of temperature, thermal conductivity, thermal diffusivity, volumetric heat capacity, and electrical impedance using simple analysis algorithms. Clinical studies on 20 patients subjected to a variety of external stimuli validate the device operation and allow quantitative comparisons of measurement capabilities to those of existing state-of-the-art tools.

  View details for DOI 10.1038/micronano.2017.14

  View details for Web of Science ID 000403040600001

  View details for PubMedID 31057861

  View details for PubMedCentralID PMC6444991

• Epidermal devices for noninvasive, precise, and continuous mapping of macrovascular and microvascular blood flow SCIENCE ADVANCES Webb, R., Ma, Y., Krishnan, S., Li, Y., Yoon, S., Guo, X., Feng, X., Shi, Y., Seidel, M., Cho, N., Kurniawan, J., Ahad, J., Sheth, N., Kim, J., Taylor, J. G., Darlington, T., Chang, K., Huang, W., Ayers, J., Gruebele, A., Pielak, R. M., Slepian, M. J., Huang, Y., Gorbach, A. M., Rogers, J. A. 2015; 1 (9): e1500701

  Abstract

  Continuous monitoring of variations in blood flow is vital in assessing the status of microvascular and macrovascular beds for a wide range of clinical and research scenarios. Although a variety of techniques exist, most require complete immobilization of the subject, thereby limiting their utility to hospital or clinical settings. Those that can be rendered in wearable formats suffer from limited accuracy, motion artifacts, and other shortcomings that follow from an inability to achieve intimate, noninvasive mechanical linkage of sensors with the surface of the skin. We introduce an ultrathin, soft, skin-conforming sensor technology that offers advanced capabilities in continuous and precise blood flow mapping. Systematic work establishes a set of experimental procedures and theoretical models for quantitative measurements and guidelines in design and operation. Experimental studies on human subjects, including validation with measurements performed using state-of-the-art clinical techniques, demonstrate sensitive and accurate assessment of both macrovascular and microvascular flow under a range of physiological conditions. Refined operational modes eliminate long-term drifts and reduce power consumption, thereby providing steps toward the use of this technology for continuous monitoring during daily activities.

  View details for DOI 10.1126/sciadv.1500701

  View details for Web of Science ID 000216598200043

  View details for PubMedID 26601309

  View details for PubMedCentralID PMC4646823