Browsing by Author "Jiang, Shan"

Now showing 1 - 4 of 4
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    Epigenomic tomography for probing spatially defined chromatin state in the brain
    Liu, Zhengzhi; Deng, Chengyu; Zhou, Zirui; Ya, Xiao; Jiang, Shan; Zhu, Bohan; Naler, Lynette B.; Jia, Xiaoting; Yao, Danfeng (Daphne); Lu, Chang (Cell Press, 2024-03-25)
    Spatially resolved epigenomic profiling is critical for understanding biology in the mammalian brain. Singlecell spatial epigenomic assays were developed recently for this purpose, but they remain costly and labor intensive for examining brain tissues across substantial dimensions and surveying a collection of brain samples. Here, we demonstrate an approach, epigenomic tomography, that maps spatial epigenomes of mouse brain at the scale of centimeters. We individually profiled neuronal and glial fractions of mouse neocortex slices with 0.5 mm thickness. Tri-methylation of histone 3 at lysine 27 (H3K27me3) or acetylation of histone 3 at lysine 27 (H3K27ac) features across these slices were grouped into clusters based on their spatial variation patterns to form epigenomic brain maps. As a proof of principle, our approach reveals striking dynamics in the frontal cortex due to kainic-acid-induced seizure, linked with transmembrane ion transporters, exocytosis of synaptic vesicles, and secretion of neurotransmitters. Epigenomic tomography provides a powerful and cost-effective tool for characterizing brain disorders based on the spatial epigenome.
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    Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement
    Chin, Ai Lin; Jiang, Shan; Jang, Eungyo; Niu, Liqian; Li, Liwu; Jia, Xiaoting; Tong, Rong (Nature Research, 2021)
    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.
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    Multimaterial multifunctional fibers for biomedical applications
    Jiang, Shan (Virginia Tech, 2021-06-08)
    The aim of my Ph.D. thesis is to summarize my research on the development of multimateiral multifunctional fibers for bio-related application, mainly in the fields of neural interfacing and bioimpedance sensing. Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires the development of improved miniaturized neural interfaces that integrate into brain tissue without altering its properties. Despite the advancement of the existing neural interface technologies such as microwires, silicon-based multielectrode arrays, and electrode arrays with flexible substrates, the physical properties of these devices limit their access to one, small brain region with single implantation. Beyond neural interfacing, extracting molecular information is crucial for understanding many neurological diseases and disorders. The most adapted methods are fast scan cyclic voltammetry and microdialysis. However, both have some limitations such as offline sensing or lack of selectivity. Furthermore, by concentrating optical fields at the nanoscale, plasmonic nanostructures can serve as optical nanoantennas to achieve ultrasensitive bio-/chemical sensing. But due to the limitation of the sensing mechanism, it is hard to perform the plasmonic sensing in live animals. Moreover, the relatively poor electrical performance of the electrode materials that can be utilized in the thermal drawing process limits the function of the fiber in other types of biomedical application, such as deep brain stimulation and electrochemical sensing. For example, the large inherent electrical resistance of the electrode material will significantly interference the electrical impedance result while the main purpose of this kind of study is to explore the frequency-dependent electrical properties of the tested subjects. To overcome above difficulties This thesis introduces broad application of multimaterial multiplexed fibers in biomedical areas. I first describe the development and application of spatially expandable multifunctional fiber-based probes for mapping and modulating brain activities across distant regions in the deep brain (Chapter 2). Secondly, I present the flexible nano-optoelectrodes integrated multifunctional fiber probes that can have hybrid optical-electrical sensing multimodalities, including optical refractive-index sensing, surface-enhanced Raman spectroscopy, and electrophysiological recording (Chapter 3). Thirdly, I demonstrate 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 (Chapter 4). The same device allows for local delivery of immune checkpoint blockade antibodies and for monitoring of clinical outcomes by tumor impedance measurement over the course of weeks with the photodynamic therapy option to enhance anti-tumor immunity and prolong intratumoral drug retention (Chapter 5). An overview future work has been summarized (Chapter 6).
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    Spatially expandable fiber-based probes as a multifunctional deep brain interface
    Jiang, Shan; Patel, Dipan C.; Kim, Jongwoon; Yang, Shuo; Mills, William A. II; Zhang, Yujing; Wang, Kaiwen; Feng, Ziang; Vijayan, Sujith; Cai, Wenjun; Wang, Anbo; Guo, Yuanyuan; Kimbrough, Ian F.; Sontheimer, Harald; Jia, Xiaoting (Nature Research, 2020)
    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.