Stanford Advisors

All Publications

  • Palette of Rechargeable Mechanoluminescent Fluids Produced by a Biomineral-Inspired Suppressed Dissolution Approach. Journal of the American Chemical Society Yang, F., Wu, X., Cui, H., Jiang, S., Ou, Z., Cai, S., Hong, G. 2022


    Mechanoluminescent materials, which emit light in response to mechanical stimuli, have recently been explored as promising candidates for photonic skins, remote optogenetics, and stress sensing. All mechanoluminescent materials reported thus far are bulk solids with micron-sized grains, and their light emission is only produced when fractured or deformed in bulk form. In contrast, mechanoluminescence has never been observed in liquids and colloidal solutions, thus limiting its biological application in living organisms. Here, we report the synthesis of mechanoluminescent fluids via a suppressed dissolution approach. We demonstrate that this approach yields stable colloidal solutions comprising mechanoluminescent nanocrystals with bright emissions in the range of 470-610 nm and diameters down to 20 nm. These colloidal solutions can be recharged and discharged repeatedly under photoexcitation and hydrodynamically focused ultrasound, respectively, thus yielding rechargeable mechanoluminescent fluids that can store photon energy in a reversible manner. This rechargeable fluid can facilitate a systemically delivered light source gated by tissue-penetrant ultrasound for biological applications that require light in the tissue, such as optogenetic stimulation in the brain.

    View details for DOI 10.1021/jacs.2c06724

    View details for PubMedID 36190898

  • A biomineral-inspired approach of synthesizing colloidal persistent phosphors as a multicolor, intravital light source. Science advances Yang, F., Wu, X., Cui, H., Ou, Z., Jiang, S., Cai, S., Zhou, Q., Wong, B. G., Huang, H., Hong, G. 2022; 8 (30): eabo6743


    Many in vivo biological techniques, such as fluorescence imaging, photodynamic therapy, and optogenetics, require light delivery into biological tissues. The limited tissue penetration of visible light discourages the use of external light sources and calls for the development of light sources that can be delivered in vivo. A promising material for internal light delivery is persistent phosphors; however, there is a scarcity of materials with strong persistent luminescence of visible light in a stable colloid to facilitate systemic delivery in vivo. Here, we used a bioinspired demineralization (BID) strategy to synthesize stable colloidal solutions of solid-state phosphors in the range of 470 to 650 nm and diameters down to 20 nm. The exceptional brightness of BID-produced colloids enables their utility as multicolor luminescent tags in vivo with favorable biocompatibility. Because of their stable dispersion in water, BID-produced nanophosphors can be delivered systemically, acting as an intravascular colloidal light source to internally excite genetically encoded fluorescent reporters within the mouse brain.

    View details for DOI 10.1126/sciadv.abo6743

    View details for PubMedID 35905189

  • Cooling the pain. Science (New York, N.Y.) Jiang, S., Hong, G. 2022; 377 (6601): 28-29


    A miniaturized, flexible cooling device can be used for precise analgesia.

    View details for DOI 10.1126/science.abm8159

    View details for PubMedID 35771916

  • Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age. Nature communications Mills, W. A., Woo, A. M., Jiang, S., Martin, J., Surendran, D., Bergstresser, M., Kimbrough, I. F., Eyo, U. B., Sofroniew, M. V., Sontheimer, H. 2022; 13 (1): 1794


    Astrocytes extend endfeet that enwrap the vasculature, and disruptions to this association which may occur in disease coincide with breaches in blood-brain barrier (BBB) integrity. Here we investigate if focal ablation of astrocytes is sufficient to disrupt the BBB in mice. Targeted two-photon chemical apoptotic ablation of astrocytes induced a plasticity response whereby surrounding astrocytes extended processes to cover vascular vacancies. In young animals, replacement processes occur in advance of endfoot retraction, but this is delayed in aged animals. Stimulation of replacement astrocytes results in constriction of pre-capillary arterioles, suggesting that replacement astrocytes are functional. Pharmacological inhibition of pSTAT3, as well as astrocyte specific deletion of pSTAT3, reduces astrocyte replacement post-ablation, without perturbations to BBB integrity. Similar endfoot replacement occurs following astrocyte cell death due to reperfusion in a stroke model. Together, these studies uncover the ability of astrocytes to maintain cerebrovascular coverage via substitution from nearby cells.

    View details for DOI 10.1038/s41467-022-29475-2

    View details for PubMedID 35379828

  • Shedding light on neurons: optical approaches for neuromodulation NATIONAL SCIENCE REVIEW Jiang, S., Wu, X., Rommelfanger, N. J., Ou, Z., Hong, G. 2022
  • Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement. Nature communications Chin, A. L., Jiang, S., Jang, E., Niu, L., Li, L., Jia, X., Tong, R. 2021; 12 (1): 5138


    Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient-response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, we develop an implantable miniaturized device using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks. The combination of local immune checkpoint blockade antibodies delivery via this device with photodynamic therapy elicits a sustained anti-tumor immunity in multiple tumor models. Our device uses tumor impedance measurement for timely presentation of treatment outcomes, and allows modifications to the delivered drugs and their concentrations, rendering this device potentially useful for on-demand delivery of potent immunotherapeutics without exacerbating toxicities.

    View details for DOI 10.1038/s41467-021-25391-z

    View details for PubMedID 34446702

  • Nano-optoelectrodes Integrated with Flexible Multifunctional Fiber Probes by High-Throughput Scalable Fabrication ACS APPLIED MATERIALS & INTERFACES Jiang, S., Song, J., Zhang, Y., Nie, M., Kim, J., Marcano, A., Kadlec, K., Mills, W. A., Yan, X., Liu, H., Tong, R., Wang, H., Kimbrough, I. F., Sontheimer, H., Zhou, W., Jia, X. 2021; 13 (7): 9156-9165


    Metallic nano-optoelectrode arrays can simultaneously serve as nanoelectrodes to increase the electrochemical surface-to-volume ratio for high-performance electrical recording and optical nanoantennas to achieve nanoscale light concentrations for ultrasensitive optical sensing. However, it remains a challenge to integrate nano-optoelectrodes with a miniaturized multifunctional probing system for combined electrical recording and optical biosensing in vivo. Here, we report that flexible nano-optoelectrode-integrated multifunctional fiber probes can have hybrid optical-electrical sensing multimodalities, including optical refractive index sensing, surface-enhanced Raman spectroscopy, and electrophysiological recording. By physical vapor deposition of thin metal films through free-standing masks of nanohole arrays, we exploit a scalable nanofabrication process to create nano-optoelectrode arrays on the tips of flexible multifunctional fiber probes. We envision that the development of flexible nano-optoelectrode-integrated multifunctional fiber probes can open significant opportunities by allowing for multimodal monitoring of brain activities with combined capabilities for simultaneous electrical neural recording and optical biochemical sensing at the single-cell level.

    View details for DOI 10.1021/acsami.0c19187

    View details for Web of Science ID 000623228500127

    View details for PubMedID 33566572

  • Neural Stimulation In Vitro and In Vivo by Photoacoustic Nanotransducers MATTER Jiang, Y., Huang, Y., Luo, X., Wu, J., Zong, H., Shi, L., Cheng, R., Zhu, Y., Jiang, S., Lan, L., Jia, X., Mei, J., Man, H., Cheng, J., Yang, C. 2021; 4 (2)
  • Thermally Drawn Stretchable Electrical and Optical Fiber Sensors for Multimodal Extreme Deformation Sensing ADVANCED OPTICAL MATERIALS Zhang, Y., Li, X., Kim, J., Tong, Y., Thompson, E. G., Jiang, S., Feng, Z., Yu, L., Wang, J., Ha, D., Sontheimer, H., Johnson, B. N., Jia, X. 2021; 9 (6)
  • Spatially expandable fiber-based probes as a multifunctional deep brain interface NATURE COMMUNICATIONS Jiang, S., Patel, D. C., Kim, J., Yang, S., Iii, W., Zhang, Y., Wang, K., Feng, Z., Vijayan, S., Cai, W., Wang, A., Guo, Y., Kimbrough, I. F., Sontheimer, H., Jia, X. 2020; 11 (1): 6115


    Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio. However, with single implantation, the physical properties of these devices limit their access to one, small brain region. To overcome this limitation, we developed a platform that provides three-dimensional coverage of brain tissue through multisite multifunctional fiber-based neural probes guided in a helical scaffold. Chronic recordings from the spatially expandable fiber probes demonstrate the ability of these fiber probes capturing brain activities with a single-unit resolution for long observation times. Furthermore, using Thy1-ChR2-YFP mice we demonstrate the application of our probes in simultaneous recording and optical/chemical modulation of brain activities across distant regions. Similarly, varying electrographic brain activities from different brain regions were detected by our customizable probes in a mouse model of epilepsy, suggesting the potential of using these probes for the investigation of brain disorders such as epilepsy. Ultimately, this technique enables three-dimensional manipulation and mapping of brain activities across distant regions in the deep brain with minimal tissue damage, which can bring new insights for deciphering complex brain functions and dynamics in the near future.

    View details for DOI 10.1038/s41467-020-19946-9

    View details for Web of Science ID 000617694900008

    View details for PubMedID 33257708

    View details for PubMedCentralID PMC7704647

  • Scalable, washable and lightweight triboelectric-energy-generating fibers by the thermal drawing process for industrial loom weaving NANO ENERGY Feng, Z., Yang, S., Jia, S., Zhang, Y., Jiang, S., Yu, L., Li, R., Song, G., Wang, A., Martin, T., Zuo, L., Jia, X. 2020; 74
  • 3D bioprinting using hollow multifunctional fiber impedimetric sensors BIOFABRICATION Haring, A. P., Jiang, S., Barron, C., Thompson, E. G., Sontheimer, H., He, J., Jia, X., Johnson, B. N. 2020; 12 (3): 035026


    3D bioprinting is an emerging biofabrication process for the production of adherent cell-based products, including engineered tissues and foods. While process innovations are rapidly occurring in the area of process monitoring, which can improve fundamental understanding of process-structure-property relations as well as product quality by closed-loop control techniques, in-line sensing of the bioink composition remains a challenge. Here, we report that hollow multifunctional fibers enable in-line impedimetric sensing of bioink composition and exhibit selectivity for real-time classification of cell type, viability, and state of differentiation during bioprinting. Continuous monitoring of the fiber impedance magnitude and phase angle response from 102 to 106 Hz during microextrusion 3D bioprinting enabled compositional and quality analysis of alginate bioinks that contained fibroblasts, neurons, or mouse embryonic stem cells (mESCs). Fiber impedimetric responses associated with the bioinks that contained differentiated mESCs were consistent with differentiation marker expression characterized by immunocytochemistry. 3D bioprinting through hollow multifunctional fiber impedimetric sensors enabled classification of stem cells as stable or randomly differentiated populations. This work reports an advance in monitoring 3D bioprinting processes in terms of in-line sensor-based bioink compositional analysis using fiber technology and provides a non-invasive sensing platform for achieving future quality-controlled bioprinted tissues and injectable stem-cell therapies.

    View details for DOI 10.1088/1758-5090/ab94d0

    View details for Web of Science ID 000549106800001

    View details for PubMedID 32434163

  • Thermally drawn advanced functional fibers: New frontier of flexible electronics MATERIALS TODAY Yan, W., Dong, C., Xiang, Y., Jiang, S., Leber, A., Loke, G., Xu, W., Hou, C., Zhou, S., Chen, M., Hu, R., Shum, P., Wei, L., Jia, X., Sorin, F., Tao, X., Tao, G. 2020; 35: 168-194
  • Flexible Multi-Material Fibers for Distributed Pressure and Temperature Sensing ADVANCED FUNCTIONAL MATERIALS Yu, L., Parker, S., Xuan, H., Zhang, Y., Jiang, S., Tousi, M., Manteghi, M., Wang, A., Jia, X. 2020; 30 (9)
  • Polymer Composite with Carbon Nanofibers Aligned during Thermal Drawing as a Microelectrode for Chronic Neural Interfaces ACS NANO Guo, Y., Jiang, S., Grena, B. B., Kimbrough, I. F., Thompson, E. G., Fink, Y., Sontheimer, H., Yoshinobu, T., Jia, X. 2017; 11 (7): 6574-6585


    Microelectrodes provide a direct pathway to investigate brain activities electrically from the external world, which has advanced our fundamental understanding of brain functions and has been utilized for rehabilitative applications as brain-machine interfaces. However, minimizing the tissue response and prolonging the functional durations of these devices remain challenging. Therefore, the development of next-generation microelectrodes as neural interfaces is actively progressing from traditional inorganic materials toward biocompatible and functional organic materials with a miniature footprint, good flexibility, and reasonable robustness. In this study, we developed a miniaturized all polymer-based neural probe with carbon nanofiber (CNF) composites as recording electrodes via the scalable thermal drawing process. We demonstrated that in situ CNF unidirectional alignment can be achieved during the thermal drawing, which contributes to a drastic improvement of electrical conductivity by 2 orders of magnitude compared to a conventional polymer electrode, while still maintaining the mechanical compliance with brain tissues. The resulting neural probe has a miniature footprint, including a recording site with a reduced size comparable to a single neuron and maintained impedance that was able to capture neural activities. Its stable functionality as a chronic implant has been demonstrated with the long-term reliable electrophysiological recording with single-spike resolution and the minimal tissue response over the extended period of implantation in wild-type mice. Technology developed here can be applied to basic chronic electrophysiological studies as well as clinical implementation for neuro-rehabilitative applications.

    View details for DOI 10.1021/acsnano.6b07550

    View details for Web of Science ID 000406649700005

    View details for PubMedID 28570813