勇于冒险 甘于艰苦 乐于和谐

Adventurous Arduous Amiable

2024-10-08 | Research

南科大肖凯课题组提出 “离子-电子”库伦拖拽效应并用于离子能源收集

       近日,南方科技大学生物医学工程系肖凯课题组在学术期刊Nature Communications上发表了题为“A nanofluidic chemoelectrical generator with enhanced energy harvesting by ion-electron Coulomb drag”的文章。生物系统通常依靠离子或者分子进行信息传输以及能量的交换和存储,而当前的信息技术依赖于电子的传输。虽然后者响应速度快,传输效率高,但磁场、高温和高湿等极端工作环境严重限制了电子器件的使用环境;与此同时,集成电路正在接近基于冯·诺依曼计算架构的摩尔定律的极限。近年来,受到生物系统的启发,基于离子-电子的耦合器件表现出优异的适应性、机械柔韧性和类生物特性,使它们成为先进智能电子设备和生物智能之间沟通的潜在桥梁。        离子-电子耦合通常发生在液体和固体界面之间。通常,耦合过程可以分为三种基本类型:双电层 (electric double layer,EDL) 电容过程;电化学氧化还原反应过程,以及赝电容过程。不同于上述被广泛研究和应用的离子-电子耦合过程,本文提出 “离子-电子”库伦拖拽效应,可实现离子电流和电子电流的直接交互和转换。库伦拖拽效应是指两个空间相近但彼此绝缘的导电层构成了电双层结构,在其中一层施加驱动电流会在另一层诱导产生开路电压,即产生层间拖拽效应。“离子-电子”库伦拖拽效应基于纳米流体内离子传输和半导体中电子传输的互相作用,进而实现离子-电子的耦合过程。具体来说,在纳米尺度下的离子移动行为可以诱导半导体中的自由电子移动,基于这一机制,本工作开发了一种纳米流体化学发电机。如图1所示,碳纳米管膜内的纳米离子流体由金属和氧气之间的自发氧化还原反应驱动。由于纳米离子流体中离子和空穴之间巨大的质量差距(105 to 106),基于动量守恒定律,大量的自由电子在碳纳米管膜中产生,进而实现了1.2 mA/cm2的放大电流。与此同时,单个纳米流体化学发电机单元可以产生~0.8 V的电压,并具有高达数十伏的线性可扩展性能。 图1. NCEG原理图及电输出特性:(a) NCEG的结构示意图:一个高度排列的多孔CNTM夹在一对金属电极之间,这对金属电极分别是金箔和含有铝衬底的导电碳带;(b) CNTM的形貌以及衬底AAO膜的XPS表征;(c)离子沿CNTM运动与CNTM中的自由电子被拖拽的离子库仑拖拽效应示意图;(d) NCEG在0.1 M NaCl电解液中产生的开路电压和短路电流密度。          众所周知,智能生物是基于离子定向流动(细胞上蛋白质通道控制离子输运)形成的电势信号(动作电位)进行信号的传递和信息的交互;和智能生物不同,固态电子器件是基于电势驱动的电子流动尽心信号的传输,如何构筑离子-电子信号交互体系进而实现生物-器件(脑-机)无障碍交互是未来人机交互愿景中最基本的科学问题。本工作报道的基于库伦拖拽效应的离子-电子耦合过程可实现“离子电流-电子电流”直接交互,有望搭建起电子信息和生物信息交流的新型高速通道。        南方科技大学为本论文第一单位,温州大学联合培养硕士生蒋义沙为论文第一作者,南科大生物医学工程系2022级博士生刘文超为论文共同第一作者,南科大王涛博士、云南大学王毓德教授、温州大学刘楠楠教授和南方科技大学副教授肖凯为论文通讯作者。本工作得到了国家重点研发计划、国家自然科学基金、广东省重点实验室项目和深圳市科技创新委员会的支持。        原文链接:https://www.nature.com/articles/s41467-024-52892-4          肖凯教授课题组(“神经仿生材料与器件”实验室)长期招聘博士后、科研助理和交流学生。课题组主要围绕“神经仿生材料、类脑计算器件、神经调控技术”开展化学、材料、电子、生物等多学科交叉研究,自2021年成立以来,课题组自主培养的学生以南科大为第一单位在Nat. Commun., Sci. Adv., Angew. Chem.,等杂志发表文章20余篇,课题组多位成员获批国自然面上项目(2项)、青年基金项目(3项)、博士后海外引才专项基金等。详细信息见课题组网站:http://www.xiaokai-group.cn/。

2024-04-10 | Research

Researchers make progress in neuro-inspired ion information devices

The biggest difference between electronic devices and brain information processing mechanisms is that the human brain is an intelligent system that uses ions as information carriers with ultra-low energy consumption and ultra-high performance. Voltage-gated ion channels, also known as life’s transistors (Figure 1), can precisely and selectively regulate ion transport and play important roles in maintaining important physiological activities and processing complex information in intelligent life. Associate Professor Kai Xiao’s research group from the Department of Biomedical Engineering (BME) at the Southern University of Science and Technology (SUSTech) has published their research on ion transistors based on ions as information carriers. Inspired by the switching mechanism of voltage-gated ion channels (i.e., life’s transistors), they successfully prepared ionic transistors based on carbon nanotubes, which can achieve ultra-high switching ratios (104) at ultra-low gate voltages. In addition, logic gates were constructed based on ionic transistors, demonstrating their application and development in ion circuits. Their work, entitled “Bioinspired carbon nanotubes-based nanofluidic ionic transistor with ultrahigh switching capabilities for logic circuits”, has been published in the journal Science Advances. Figure 1. Life’s transistors and how to construct ionic transistors through nanofluidic systems The research group reported a nanofluidic ionic transistor based on carbon nanotubes, which exhibits an on/off ratio of 104 at an operational gate voltage as low as 1 V (Figure 2). By controlling the morphology of carbon nanotubes, both unipolar and ambipolar ionic transistors are realized, and their on/off ratio can be further improved by introducing an Al2O3 dielectric layer. Meanwhile, this ionic transistor enables polarity switching between p-type and n-type by controlled surface properties of carbon nanotubes. The implementation of constructing ionic circuits based on ionic transistors is demonstrated, which enables the creation of NOT, NAND, and NOR logic gates. Figure 2. Bioinspired design and switching state of nanofluidic ion transistor The researchers provide a comprehensive overview of the first generation of bioinspired ionic transistors, including their operating mechanisms, device architecture development, and property characterizations. Despite its infancy, significant progress has been made in the applications of ionic transistors in fields such as DNA detection, drug delivery, and ionic circuits. Challenges and prospects of full exploitation of ionic transistors for a broad spectrum of practical applications are also discussed (Figure 3). Nature has chosen ions as the information carrier for the human brain, and the close coordination of various ion channels on nerve cells has formed the advantage of fast computing and low energy consumption in the human brain. Inspired by nature, ion information devices, compared to electronic devices, are still in their early stages and have shown enormous application prospects. They expect ion transistors to play important roles in the near future in the concentration or separation of ions and molecules in seawater and physiological disease detection in clinical medicine. Additionally, nanofluidic systems can aim to mimic the energy-efficient information processing of the human brain (such as various pulse signals based on action potentials, biological oscillations, long-term and short-term memory, etc.). This provides significant advantages for implantable nanofluidic devices and barrier-free brain-computer interfaces. Figure 3. Application and outlook diagram of ionic transistor Exploring artificial devices that precisely control ion transport will promote the development of ultra-low-energy information technology based on ion systems, and have broad application prospects for ion sensing, low-energy neuromorphic computing, and brain-machine interfacing. The research group has also made a series of progress in the construction of ion information devices, which have been published in top journals, including Angewandte Chemie International Edition, Device, and ACS Nano.   Wenchao Liu, a doctoral student from the Department of BME at SUSTech, is the first author of the paper. Research Assistant Tingting Mei from the Department of BME at SUSTech and Zhouwen Cao from the National Center for Nanoscience and Technology (NCNST) at the University of Chinese Academy of Sciences (UCAS) are the co-first authors. Associate Professor Kai Xiao is the corresponding author, while Associate Researcher Ruotian Chen from the Dalian Institute of Chemical Physics at UCAS and Associate Researcher Bin Tu from NCNST, UCAS are the co-corresponding authors. SUSTech is the first affiliated unit of the paper, with collaborative units including the Technical Institute of Physics and Chemistry at UCAS, along with the Department of Mechanics & Aerospace Engineering and the Department of Materials Science & Engineering at SUSTech. This work was supported by the National Key Technologies R&D Program of China, National Natural Science Foundation of China (NSFC), Shenzhen Science and Technology Innovation Committee, Shenzhen Science and Technology Program, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Starting Grant from SUSTech, and the Strategic Priority Research Program of the Chinese Academy of Sciences.   Paper link published in Science Advance: https://www.science.org/doi/10.1126/sciadv.adj7867   Related links: Angewandte Chemie International Edition: https://doi.org/10.1002/anie.202401477 Device: https://www.sciencedirect.com/science/article/pii/S2666998624000565‍ ACS Nano: https://pubs.acs.org/doi/10.1021/acsnano.3c06190

2024-03-21 | Research

SUSTech holds launch meeting for National Key R&D Program

The National Key R&D Program “Synthetic Biology”, which is being led by the Southern University of Science and Technology (SUSTech), held a meeting on its project’s commencement and implementation plan at the University. In attendance at the meeting were Jinqiang TIAN, Deputy Director of Life Sciences and Frontier Technology at the China National Center for Biotechnology Development, Bo YUAN, Deputy Director of the Frontier Technology Working Group of the Shenzhen Science and Technology Innovation Commission (SZSTI), and Xueming YANG, Vice President of SUSTech. Accompanying them were Mingzhou GUO, a project expert, and Hanmei XU, a consulting expert, alongside other experts and researchers in this field. Jinqiang TIAN provided an analysis of the “Synthetic Biology” project, highlighting its goals, vision, and strategic task deployment. He outlined specific requirements and suggestions for various research institutions involved. Bo YUAN emphasized SZSTI’s commitment to project development and planning, encouraging the lead unit and responsible individuals to oversee the project’s smooth execution as planned. Xueming YANG briefed the expert team on SUSTech’s scientific research landscape and expressed high expectations for the innovative results and technologies that would emerge from the project. Lu ZHANG, Associate Professor of the Department of Biomedical Engineering at SUSTech and project leader, presented a comprehensive report detailing the project’s core research objectives, technical indicators, and implementation strategy. Following in-depth discussions among the experts, it is believed that this project will solve the inherent challenges of in vivo cell engineering and facilitate breakthroughs in the field of synthetic biomedicine.

2024-03-13 | Research

Researchers report organic fluorophores for rapid nucleic acid or protein assays

Jingkai YANG | 03/12/2024   Organic small-molecule fluorophores have attracted increasing attention in biosensing, disease diagnostics, semiconductor material, and dye-sensitized solar cells due to their flexible chemical structure and adjustable optical performance. So far, although plenty of excellent organic small-molecule fluorescent dyes have been developed, the detection of these dyes’ signals still requires filters and optoelectronic equipment, limiting their application in scenarios with simple settings. This is due to the established dyes, designed mainly based on a few classical fluorophore motifs, tend to exhibit small Stokes shift (typically < 30 nm, such as rhodamine, fluorescein, boron dipyrromethene (BODIPY), cyanine) or show large Stokes shifts but low brightness (such as naphthalimide or coumarin). Associate Professor Bo Zhang’s research group from the Department of Biomedical Engineering (BME) at the Southern University of Science and Technology (SUSTech) has recently published a paper that reports a block-building molecular engineering strategy for small-molecule fluorophores and synthesized a series of fluorescent dyes (named PTs) with large Stokes shifts, tunable wavelengths, and balanced brightness, enabling rapid nucleic acids/proteins assays with high sensitivity visible to naked eye. Their work, entitled “Organic Fluorophores with Large Stokes Shift for the Visualisation of Rapid Protein and Nucleic Acid Assays”, has been published in the renowned international chemistry journal Angewandte Chemie International Edition (Angew. Chem. Int. Ed.). Figure 1. A Block-building molecular engineering strategy for designing small-molecule fluorophores with large Stokes shift and applications in visualization of rapid protein and nucleic acid assays. Dye chemistry is rapidly evolving from trial-and-error to molecular engineering, emphasizing function-oriented design and synthesis of structures at the molecular level. In this work, a series of small-molecule fluorophores (named PTs) were designed and synthesized via a block-building molecular engineering strategy. They merge phenothiazine moiety with EDOT moiety by π-conjugation, which exhibits long Stokes shift (up to 262 nm), large molar extinction coefficients (ε, 30,000~100,000 M-1cm-1 in DMSO), high quantum yields (Φ, up to 54.8% in DMSO), and flexible wavelength tunability (from visible to near-infrared). The team also explored the relationship between the electronic energy levels and optical properties of PTs, and according to density-functional theory (DFT), the stacking of molecular blocks and the introduction of electron-absorbing groups can modulate the HOMO-LUMO gap. In addition, the electronic excited states of PTs calculated by Time-dependent density functional theory (TDDFT) are in agreement with the experimental data. Figure 2. Energy level calculation and electron cloud distribution calculation of PTs by density function theory. (a) Correlation between the LUMO-HOMO energy gap and excitation wavelength of PTs in experiments; (b) LUMO-HOMO energy and electron cloud distribution of PT-1, PT-5, PT-7; (c) LUMO-HOMO energy and electron cloud distribution of PT-8, PT-10, PT-11, PT-12. PTs dyes were made into fluorescent nanoparticles (PT-NPs), and observed the number of dye molecules encapsulated in a single nanoparticle can reach one million. These bright PT-NPs were applied to lateral flow assay (LFA). Consequently, direct visualization of rapid nucleocapsid (N) protein detection of SARS-CoV-2 with 100-fold sensitivity improvement over colloidal gold-based LFA was achieved, and the limit of detection was 20 fM. This assay was able to pick up more RT-PCR-confirmed SARS-CoV-2 infected clinical samples compared to colloidal gold-based LFA. Besides, the sensitivity of PT-NPs-based LFA also surpasses reported LFAs with various luminescent materials for SARS-CoV-2 detection. Figure 3. Lateral flow immunochromatography based on PT-NPs for SARS-CoV-2 antigen detection. (a) Schematic diagram of the detection system; (b) Comparison of sensitivity between the present work and colloidal gold assay; (c) Detection curve of the colloidal gold assay; (d) Detection curve of the present work’s assay system; (e) Specificity of the present work’s LFA system; (f-h) Analysis of the clinical assays of the colloidal gold assay and the present work’s LFA. Since May 2022, the monkeypox epidemic (Mpox) has swept through more than 100 countries and regions, and has been classified as a “Public Health Emergency of International Concern”. In this work, the researchers screened the conserved sequences of monkeypox virus genome by loop-mediated isothermal amplification (LAMP) and designed primer structures adapted to the LFA system based on PT-NPs, which enabled rapid visual nucleic acid detection of monkeypox virus (MPXV) at the single-copy level. Figure 4. PT-NPs-based lateral flow immunochromatography combined with LAMP technology for monkeypox virus nucleic acid detection; (a) Monkeypox virus nucleic acid detection target sequences; (b) Design of LAMP primer probes for monkeypox virus detection; (c) Schematic diagram of the flow of monkeypox virus nucleic acid detection based on PT-NPs and LAMP; (d) Monkeypox virus detection visualisation of the results of the rapid detection, with a sensitivity of up to single copy; (e) Specificity of the detection system. Sensitivity up to a single copy; (e) Specificity of the detection system. Since the synthesis of the first unnatural small-molecule fluorescent dye, fluorescein, by humans at the end of the 19th century, dye chemistry has gradually evolved from a trial-and-error process to a disciplined molecular engineering design. This study explores the molecular engineering design of large Stokes shift organic fluorescent dyes, providing an organic conjugated modular design strategy for dye chemistry, as well as new fluorescent materials for in vitro diagnostics to reduce the reliance on expensive optical devices. Master’s students Jingkai Yang and Ziyi Xu, both from the Department of BME at SUSTech, are the first and co-first authors of this paper, respectively. Associate Professor Bo Zhang is the corresponding author, while Professor Pan-Lin Shao from Guangzhou Medical University (GMU) and Research Assistant Professor Ying Liu from the Department of BME at SUSTech are the co-corresponding authors. SUSTech is the first affiliated unit of the paper. This work was supported by the National Natural Science Foundation of China (NSFC), Guangdong Fund for Basic and Applied Basic Research, Shenzhen Science and Technology Programme, and Guangdong Key Laboratory of Advanced Biomaterials.   Paper link: https://doi.org/10.1002/anie.202318800

2023-12-13 | Teaching

Second “BME Cup” Speaking Contest showcases students’ vision for health care and future society

In a display of intellectual prowess and fluent oratory skills, ten undergraduate and postgraduate students from various departments participated in the Second “BME Cup” Speaking Contest. The event, held jointly by the Center for Language Education (CLE) and the Department of Biomedical Engineering (BME) at the Southern University of Science and Technology (SUSTech) on December 3, 2023, provided an invaluable platform for participants to share their unique perspectives on health care and the future society. Under the theme of “Health Care and Future Society”, contestants captivated the audience with their profound understanding of how breakthroughs in science and technology can be harnessed to safeguard people’s health. Each participant delved into thought-provoking discussions surrounding health, healthcare systems, and the role of innovation in shaping our society’s well-being in the future. Throughout the competition, the contenders skillfully navigated complex subjects such as CAR-T therapy, tissue cryopreservation, implantation restoration, electronic skin, and technology and healthcare. They eloquently discussed the potential of these advancements to revolutionize the healthcare industry and improve the overall quality of life for individuals across the globe. The panel of judges, comprised of three English teachers from CLE and three faculty members from the Department of BME, evaluated each presentation based on content, delivery, and overall impact. The audiences were impressed by the depth of technology and understanding demonstrated by the contestants and their ability to convey complex concepts in an accessible manner. The Second “BME Cup” Speaking Contest succeeded in fostering an environment that encouraged critical thinking and collaborative problem-solving. The event not only served as a platform to recognize exceptional students but also highlighted the significance of interdisciplinary approaches in addressing the challenges of our rapidly evolving society. As the contest came to a conclusion, CLE and the Department of BME expressed their confidence in the potential impact these talented individuals will have in their fields. This impressive demonstration of intellect and communication skills has set a high standard for future editions of the “BME Cup” Speaking Contest.   Center for Language Education

2023-10-13 | Research

Researchers overcome challenge of oral absorption of large molecules using bioinspired drug delivery approach

As biotechnology advances, large-molecule drugs such as peptides, proteins, and nucleic acids are increasingly gaining widespread clinical applications. These macromolecular agents display superior targeting and therapeutic efficacy compared to small-molecule drugs, and are applicable to a variety of diseases that threaten human health, including cardiovascular diseases, diabetes, and cancer. However, one significant obstacle is their susceptibility to degradation in the gastrointestinal tract and their large molecular size, which hampers effective oral absorption. Despite considerable research investment in developing new delivery technologies over the past decades, very few orally administered peptide-based drugs have received FDA approval. For instance, the oral formulation of semaglutide, Rybelsus, approved by the FDA in 2020, still has a bioavailability of less than 1%, even after the addition of a multitude of absorption-promoting agents. To address this challenge, recent research efforts have sought to develop devices that can directly inject the drug into the gastrointestinal mucosa. However, the stability and safety of these technologies remain under scrutiny.   A team led by Associate Professor Zhi Luo of the Department of Biomedical Engineering at the Southern University of Science and Technology (SUSTech) has recently published a study inspired by the unique structure and efficient absorptive properties of octopus suckers, that leverages 3D printing technology to design a non-invasive oral drug delivery device. Their research paper, entitled “Boosting systemic absorption of peptides with a bioinspired buccal-stretching patch”, has been published in the journal Science Translational Medicine. The technology created by the researchers mimics the three-dimensional structure and muscle arrangement of octopus suckers to achieve gentle but effective adhesion and stretching on the oral mucosa. This mechanical force can reversibly disrupt the epithelial cell structure and destroy the lipid barrier, thereby facilitating the efficient diffusion of peptide molecules. Furthermore, this delivery device can be loaded with various types of excipients, including absorption promoters and release modifiers, to achieve controlled release of peptide drugs. Thus, through the synergistic action of mechanical stretching and chemical absorption enhancers, this formulation method efficiently diffuses the drug into the highly vascularized mucosal tissue, promoting its entry into the systemic circulation. This work also marked improvement in bioavailability: In in vivo studies using a large animal model (beagle dogs), the bioinspired suction patch demonstrated two orders of magnitude increase in the bioavailability of desmopressin, a peptide drug whose oral bioavailability is only 0.1%, compared to commercial tablet formulations. For semaglutide, this formulation showed bioavailability comparable to the FDA-approved Rybelsus tablets. Representing a novel oral peptide drug formulation, a PCT patent application has been submitted for this work. The formulation is a non-invasive drug delivery technology with a simple, highly flexible process suitable for the delivery of various large-molecule drugs. Human trials involving 40 healthy participants verified the high acceptability of the new formulation, indicating substantial clinical translational potential. The study offers a novel and practical approach to resolving the challenges of oral absorption of large-molecule drugs. The synergistic effect of mechanical stretching and chemical absorption enhancers introduces a novel mechanism for the oral delivery of macromolecular drugs. This delivery modality has the potential to become a platform technology for various types of macromolecular drug formulations, providing more convenient and effective treatment options for patients. Assoc. Prof. Zhi Luo is the first and corresponding author of this paper, and SUSTech is the first affiliation unit. Prof. Jean-Christophe Leroux at the Swiss Federal Institute of Technology in Zurich is a co-corresponding author. This work was supported by the National Key Research and Development Program of the Ministry of Science and Technology and the Guangdong Provincial Key Laboratory of Biomaterials, among other projects.   Paper link: https://www.science.org/doi/10.1126/scitranslmed.abq1887

2023-09-27 | Research

Researchers develop portable SARS-CoV-2 variant monitoring technology

The continuous mutations of the novel coronavirus (SARS-CoV-2) are complicating public health responses and vaccination strategies. Portable assays for the rapid identification of lineages of SARS-CoV-2 are needed to aid large-scale efforts in monitoring the evolution of the virus. Virus mutations remain a significant challenge for both scientific research and public health, especially as the global pandemic continues to spread. Traditional detection methods, like RT-qPCR, have limitations in identifying multiple viral mutations. Given the rapid mutation of the coronavirus and the varying efficacy of vaccines against new variants, more precise detection techniques are critical. In response to this urgent situation, Associate Professor Bo Zhang’s group from the Department of Biomedical Engineering (BME) at the Southern University of Science and Technology (SUSTech), in collaboration with Professor Hongjie Dai from Stanford University, Director Jing Yuan from the Third People’s Hospital of Shenzhen, the Microfluidic-Biomaterials Lab at SUSTech, and Dr. Meijie Tang from Nirmidas Biotech, have developed a novel SARS-CoV-2 variant detection technology called FEMMAN. This technology uses advanced methods combining nanotechnology and biosensors, allowing not just accurate detection but differentiation among dozens of different mutations. Their research work, entitled “Multiplexed discrimination of SARS-CoV-2 variants via plasmonic-enhanced fluorescence in a portable and automated device”, has been published in the journal Nature Biomedical Engineering, offering a potential game-changer in the diagnosis and monitoring of COVID-19 variants. FEMMAN Technology FEMMAN integrates various cutting-edge technologies, such as plasmonic gold nanomaterials, DNA microarrays, and microfluidic chips, to successfully identify SARS-CoV-2 and its multiple variants with high sensitivity and specificity. The technology’s flexibility and accuracy make it a powerful tool for future pandemic control efforts. Moreover, FEMMAN can rapidly adapt to newly emerging virus variants, substantially enhancing the accuracy and efficiency of pandemic responses and helping in precise risk assessment and resource allocation worldwide. Figure 1. FEMMAN achieves single-RNA copy sensitivity with Asy-RT–RPA for the detection of SARS-CoV-2 and the simultaneous discrimination of viral variants with SNV distinction Unique Features The unique feature of FEMMAN technology lies in its multiplex detection capabilities. Prof. Zhang’s team further optimized the technique to adapt to newly emerging virus variants. In essence, FEMMAN is not only a highly sensitive and specific detection tool but also a highly flexible and scalable platform for multiplex nucleic acid detection. Figure 2. Comprehensive identification of SARS-CoV-2 lineages by FEMMAN The breakthrough was made possible by interdisciplinary and inter-institutional collaborations. The project team solved multiple key scientific challenges by drawing upon their years of professional expertise. In collaboration with Director Jing Yuan’s team from the Third People’s Hospital of Shenzhen, thousands of clinical trials were conducted, allowing FEMMAN technology to move quickly from the lab to the clinic and to potentially be widely applied in various settings, including hospitals, airports, schools, and communities. Figure 3. SARS-CoV-2 detection and viral-lineage discrimination of clinical samples with FEMMAN Societal Impact When asked about the social implications of the research, the first author of the paper, Dr. Ying Liu, said: “The emergence of FEMMAN technology gives us a much more robust weapon against the constant mutations of the novel coronavirus. This is particularly crucial as many regions globally face insufficient testing resources and immense pressures on healthcare systems.” The scalability of FEMMAN technology also means it has broad application prospects. Aside from COVID-19, it could potentially be used to detect a variety of other viruses and microbes, including but not limited to influenza, Ebola, and Zika viruses. Research Assistant Professor Ying Liu from the Department of BME at SUSTech is the first author of this paper. Yang Yang, Guanghui Wang, and Dou Wang are co-first authors. Associate Professor Bo Zhang from the Department of BME at SUSTech, Academician Hongjie Dai from Stanford University, Director Jing Yuan from the Third People’s Hospital of Shenzhen, and Dr. Meijie Tang from Nirmidas are the corresponding authors. SUSTech is the primary institution for this research, and collaborating institutions include Stanford University, Third People’s Hospital of Shenzhen, Nirmidas Inc., and Guangzhou Medical University. This work was supported by the National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Shenzhen Science and Technology Programme Project, Guangdong Provincial Key Laboratory of Advanced Biomaterials, National Key R&D Program of China, National Science and Technology Major Project, and the Shenzhen High-Level Hospital Construction Fund. Technical support for this research was provided by the Core Research Facilities at SUSTech.   Paper link: https://www.nature.com/articles/s41551-023-01092-4

2023-03-01 | Research

Researchers make advances in field of transarterial chemoembolization modeling for liver cancer treatment

Hepatocellular carcinoma (HCC) accounts for more than 90% of primary liver cancer and remains a worldwide health problem due to its aggressive and lethal nature. Transarterial chemoembolization (TACE) is the first-line treatment for unresectable HCC. This treatment involves the embolization of tumor vessels and the delivery of high-concentration chemotherapy drugs, which are locally released into the tumor tissues to promote tumor necrosis. However, the therapeutic effect of this method has always been controversial. Therefore, designing an ideal embolization model to evaluate the pharmacokinetics inside the tumor site and accurately evaluate the therapeutic effects of clinically relevant embolization agents is of great significance.     Assistant Professor Qiongyu Guo’s team from the Department of Biomedical Engineering and Assistant Professor Xiaoying Tang’s team from the Department of Electronic and Electrical Engineering at the Southern University of Science and Technology (SUSTech) have recently collaborated on the publication of a visualized 3D tumor-mimicking chemoembolization model. The model, which combines deep learning and graph analysis methods, has made significant progress in the construction of an ex vivo organ-structured evaluation platform for liver cancer chemoembolization treatment. Their research results, entitled “A 3D Tumor-Mimicking in Vitro Drug Release Model of Locoregional Chemoembolization Using Deep Learning Based Quantitative Analyses,” have been published in Advanced Science.   Figure 1. Schematic diagram of the 3D embolization model based on deep learning.   Prof. Qiongyu Guo’s and Prof. Xiaoying Tang’s teams collaborated to design a 3D tumor-mimicking drug release model through utilizing decellularized liver organ as a drug-testing platform (Figure 1). The model contains three key features that affect drug release in vivo: a complex vascular system, a drug-diffusible electronegative extracellular matrix, and controllable drug depletion. This drug release model, combined with deep learning-based computational analyses for the first time, permits quantitative evaluation of all important parameters associated with locoregional drug release. The U-shaped segmentation network based on attention mechanism and adversarial training can achieve accurate segmentation of the embolized vascular region with few annotated samples. A series of image processing and graph analysis algorithms were combined to achieve an accurate and automatic quantitative statistical analysis of drug loss. To further verify the feasibility and accuracy of the model, the study quantitatively analyzed the endovascular embolization distribution, intravascular drug retention, and extravascular drug diffusion, establishing an in vivo-in vitro correlation with in-human results up to 80d. Using the established 3D tumor-mimicking model, the in vitro chemoembolization efficacy of three different formulations of doxorubicin solution was systematically evaluated (Figure 2). The researchers used image processing algorithms to extract the skeleton of the segmented embolized vessels and constructed a custom multi-level tree. Subsequently, quantitative analysis and statistical comparison were performed at different tree levels, allowing for a clear depiction of the differences in embolization depth and changes in residual drugs within blood vessels for the three formulations over 80 days.   Figure 2 Vessel topological analyses. Skeleton extraction and classification of drug-containing vessels of three drug formulations, i.e., DOX Ctrl, EO-DOX, and DEB, tested in the DLM model over 80 d. DOX: doxorubicin solution; EO-DOX: emulsion of ethiodized oil and doxorubicin solution; DEB: drug eluting bead.   The local drug concentration within tumors is an important factor in determining their therapeutic efficacy. Taking advantage of the visualization capabilities of the 3D model and the strong self-fluorescence of doxorubicin at low concentrations, the researchers determined the extracellular drug diffusion depth as compared to the drug diffusion behavior observed in in vivo experiments. They found that the drug diffusion depth in this 3D model exhibited great linearity with the in-human results, validating the effectiveness of the embolic chemotherapy model for in vivo–in vitro consistency evaluation. This has important guiding significance for the development of new drug formulations and evaluation of embolic chemotherapy efficacy in clinical practice (Figure 3). Figure 3 Extravascular drug diffusion of drug eluting beads in DLM model and IVIVC.   Dr. Xiaoya Liu, a postdoctoral fellow from the Department of Biomedical Engineering at SUSTech, and Xueying Wang, a master’s student from the Department of Electronic and Electrical Engineering at SUSTech, are the first authors of this paper. Asst. Prof. Qiongyu Guo and Asst. Prof. Xiaoying Tang are the corresponding authors. SUSTech is the corresponding institution of the paper. Other collaborating authors included master’s students Yucheng Luo, Meijuan Wang, and Xiaoyu Han, all from SUSTech. This work was supported by the National Natural Science Foundation of China (NSFC), Guangdong Innovative and Entrepreneurial Research Team Program, Science, Technology and Innovation Commission of Shenzhen Municipality, and SUSTech.   Paper link: https://onlinelibrary.wiley.com/doi/10.1002/advs.202206195?af=R

2023-02-24 | Research

Researchers make progress in whole-cell high-throughput 3D super-resolution imaging across large field of view

While fluorescence microscopy with high contrast and super-resolution has revolutionized structural cell biology studies, high-throughput imaging with rich information content has enabled quantitative biology research. An emerging trend is developing high-throughput super-resolution imaging techniques for high-content screening. However, field-dependent aberrations restrict the field of view (FOV) of super-resolution imaging to only tens of micrometers.     Associate Professor Yiming Li from the Advanced Microscopy Imaging Laboratory in the Department of Biomedical Engineering at the Southern University of Science and Technology (SUSTech) led a team to develop a deep learning algorithm framework to address the field-dependent aberrations and bypass the bottleneck for large FOV imaging. Their research results, entitled “Field-dependent deep learning enables high-throughput whole-cell 3D super-resolution imaging,” has been published in Nature Methods. The researchers developed a deep learning method for precise localization of spatially variant point emitters (FD-DeepLoc) over a large FOV covering the full chip of a modern sCMOS camera. Using a graphic processing unit (GPU) based vectorial PSF fitter, they can fast and accurately model the spatially variant point spread function (PSF) of a high numerical aperture (NA) objective in the entire FOV. Combined with deformable mirror-based optimal PSF engineering, they demonstrate high-accuracy 3D SMLM over a volume of ~180 × 180 × 5 μm3, allowing people to image mitochondria and nuclear pore complexes in entire cells in a single imaging cycle without hardware scanning – a 100-fold increase in throughput compared to the state-of-the-art. This work provides new technical ideas and perspectives for the field of super-resolution microscopy. It also has important theoretical and practical value for the study of nanoscale biological structures in complete cell populations or tissues.   Figure 1. Large FOV imaging of cellular nuclear pores   Shuang Fu and Wei Shi, doctoral students at SUSTech, are the co-first authors of this paper. Assoc. Prof. Yiming Li is the corresponding author, and SUSTech is the first affiliation. This work was supported by the Key Technology Research and Development Program of Shandong, Science, Technology and Innovation Commission of Shenzhen Municipality, and Start-Up Fund from SUSTech.   Paper link: https://www.nature.com/articles/s41592-023-01775-5

2022-08-11 | Research

Researchers make series of advances in field of ionic neuromorphic devices

In nature, the transmission and processing of information, as well as the energy conversation and storage, are often mediated and regulated using ions and fluids transportation at small scales (e.g., nanopores). It can be said that the language of intelligent life is “ions”, and the language of artificial intelligence is “electrons”. To realize seamless communications between intelligent life and artificial intelligence, building an artificial intelligence system with “ions” as language is necessary. We should fabricate artificial nanopores on the nanoscale to realize controllable ions transport, which is common in the biological nanopore. On a microscale, it is significant to build an artificial neuron to replicate the generation of the action potential by ions transport. On a macroscale, the construction of a bioinspired neural network is necessary to realize ionic signal transmission and information storage. Associate Professor Kai Xiao’s research team from the Department of Biomedical Engineering at the Southern University of Science and Technology (SUSTech) has made progress on this topic by achieving a series of advances in the field of Bio-inspired Multiscale Ionic Neuromorphic Devices. Their subsequent papers have been published in top international journals such as Nature Communications, CCS Chemistry, Advanced Science, and ACS Nano. Ionic diode property widely exists in the biological nanopore of intelligent living organisms. To control ions transport unidirectional, cells living organisms can realize a series of physiological activities such as the generation of action potentials and the control of cell osmotic pressure. To realize ionic diode properties in vitro, Prof. Xiao’s team fabricated a carbon-based nanofluid with multiple scales and realized ionic diode properties with an ionic rectification ratio (on-off ratio) of more than 10,000. This work breaks the existing diode mode of “silicon materials + electrons”, and builds a life-like new diode model of “carbon materials + ions”. This lays a good foundation for the construction of ion transport-based logic circuits and derives ion transport-based transistors and neurons. The related research results, entitled “Unidirectional ion transport in nanoporous carbon membranes with a hierarchical pore architecture,” were published in Nature Communications. Figure 1. Carbon-based nanofluids with multiple scales and its ionic diode properties An ion pump is a unique function of intelligent life. It can realize the reverse concentration gradient transport of ions by consuming external energy. This progress is important for many physiological activities, such as photosynthesis, ATP synthesis, and action potential generation. How to construct a biomimetic ion pump can lay a good foundation for the technological breakthrough of various devices such as ion transport-based photoelectric energy conversion and neural signal regulation. In their earlier research (Nat. Commun. 2019, 10, 74; Natl. Sci. Rev. 2021, 8, nwaa231.), the researchers realized a series of biomimetic ion pump functions and applications by constructing a nanofluidic system based on semiconductor materials. Most recently, they proposed that biomimetic ion pumps can be constructed by introducing asymmetric elements into a nanofluids system. For example, for the widely studied biomimetic light-driven ion pumps, light-driven ion pump properties can be realized by the asymmetric photoelectric effect, photothermal effect, and photochemical reaction, respectively This study, entitled “Light-Driven Ion Transport in Nanofluidic Devices: Photochemical, Photoelectric, and Photothermal Effects,” was published in CCS Chemistry. Figure 2. Compared to electrons, ions have many unique advantages in designing energy and information devices. For example, various valencies, different sizes, and diverse polarizabilities. These characterizations enable all energy and information processors constructed by electrons to be redefined by ions. In recent years, with the development of artificial intelligence (AI) and a deeper understanding of biological intelligence, researchers have found that devices based on electron transport have significant limitations in the process of realizing human-computer interaction. By learning from nature, constructing ions transport-based energy and sensor devices can lay a good foundation for developing the next-generation brain-computer interface and realizing seamless human-computer interaction. This research topic involves interdisciplinary fields such as chemistry, materials, devices, and biology. Prof. Xiao’s research group was invited to publish a series of reviews and perspectives on how to construct nanoionic devices to realize the functions that nanoelectronic devices cannot satisfy. These reviews, entitled “Nanoionics from Biological to Artificial Systems: An Alternative Beyond Nanoelectronics” and “Solid-State Iontronic Devices: Mechanisms and Applications,” were published in Advanced Science and Advanced Materials Technologies, respectively. They pointed out that ions can realize many of the functions that nanoelectronics can achieve. By learning from intelligent life, nanoionics devices also can realize some functions that nanoelectronics cannot. Meanwhile, these perspective articles analyze and compare the advantages and disadvantages of various devices based on ions and electrons. Based on ion transport, they predict that biomimetic nanoionic devices will be another research hotspot following nanoelectronic devices. Dr. Jianrui Zhang, Dr. Tianming Li, Ms. Tingting Mei, and Ms. Hongjie Zhang are the first authors of the above papers and reviews. Assoc. Prof. Kai Xiao is the corresponding author, while SUSTech is the first affiliation. This work was supported by the National Key Research of China.   Paper and related links (In order of appearance above): Nature Communications: https://www.nature.com/articles/s41467-021-24947-3 CCS Chemistry: https://www.chinesechemsoc.org/doi/full/10.31635/ccschem.021.202101297 Advanced Science: https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202200534 Advanced Materials Technologies: https://onlinelibrary.wiley.com/doi/10.1002/admt.202200205 Prof. Kai Xiao’s group webpage: http://www.xiaokai-group.cn/

Contacts Us

Faculty Research Building 2, 1088 Xueyuan Rd, Nanshan District, Shenzhen, Guangdong 518055, China

bme@sustech.edu.cn

关注微信公众号