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

The project “Flexible Electronic Materials for Controlled Drug Release and Tissue Regeneration Devices” led by Prof. Zhi LUO, Associate Professor of the Department of Biomedical Engineering, was approved by the Ministry of Science and Technology of China. Born in 1991, Prof. LUO is the youngest chief scientist of the National Key R&D Program of SUSTech.

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/

A team of students from the Southern University of Science and Technology (SUSTech) recently won the Gold Award and the Best Website Award in China’s first synthetic biology innovation competition, SynBio Challenges 2022.

The competition was sponsored by the Synthetic Biology Branch of the Chinese Society of Bioengineering, which aims to provide a platform for young students to communicate, learn, innovate, create, and cultivate their knowledge in synthetic biology, life sciences, and interdisciplinary disciplines.

Twenty-seven teams from 21 universities and colleges across the country participated in SynBio Challenges 2022, and more than 2.2 million people viewed the event online.

The SUSTech team, titled “SUSTech_Shenzhen_HCL”, was led by Prof. Ho Chun Loong from the Department of Biomedical Engineering as the Principal Investigator, Jun CHEN and Xinyi CHEN as the instructors, and Liqing YU, Songlin SHI, and Yehan WANG as the team leaders.

In addition, 14 members from different majors, including Yingxuan GONG, Xianxian WANG, Yijie WANG, Siqi MEN, Hongqiu LEI, Jiayi LIU, Nanfei JIANG, and Xuancheng MO, formed the multidisciplinary team.

Cholera is an acute diarrheal illness caused by infection of the intestine with Vibrio cholerae bacteria, which can cause dehydration and death in severe cases.

The illness is associated with dysregulation of the gut microbiota, so modulation of the gut microbiota could be a treatment for cholera.

Through genetic engineering technology, the SUSTech_Shenzhen_HCL team used Lactobacillus and Escherichia coli (E. coli) bacteria as carriers. They developed a probiotic system that can prevent and treat through the group effect between bacteria. As a result, the team won the Gold Award and the Best Website Award.

On April 22-23, 2022, the World Association for Chinese Biomedical Engineers (WACBE) held its 10^th World Congress on Bioengineering. The virtual event was hosted by the Department of Biomedical Engineering (BME) at the Southern University of Science and Technology (SUSTech).

Many experts and scholars presented plenary and keynote reports during the congress, which attracted many young scholars from different disciplinary and research backgrounds to participate in the event.

The conference promotes the exchange of the latest research results in the field of biomedical engineering and enhances the intersection and integration of related disciplines.

The WACBE World Congress on Bioengineering is an annual event that focuses on biomedical engineering approaches that drive innovative technologies and foster solutions. The congress attracts about 400 delegates from all over the world, including academic researchers, industry leaders, medical experts, and trainees.

Yekkuni L. BALACHANDRAN | 22/12/2021

Controlling the spread of the human immunodeficiency (HIV) virus might be the only feasible route for completely avoiding the intractable disease. However, crucial immunities are still difficult to be sufficiently triggered by vaccines alone, which greatly limits its practical application.

Researchers from the Microfluidic-Biomaterials Lab at the Southern University of Science and Technology (SUSTech) have developed a two-dimensional nano-adjuvant comprising of rare-earth elements that improve the immunities generated by vaccines (HIV DNA vaccine in this case).

The research article, titled “Two-dimensional nanosheets as immunoregulator improve HIV vaccine efficacy,” was published in Chemical Sciences, a scientific journal covering all aspects of chemistry.

Introducing applicable immunoregulatory building blocks to endow planar materials with inherent immunoregulatory characteristics is a strenuous task. Some rare earths or rare-earth based complexes, because of their inherent immunoregulatory capability, can regulate the behavior of macrophages (antigen-representing cells) and immunity. Considering that multiple types of rare earths have immunoregulatory effects on the functions or behaviors of immune effector cells, selecting rare earths rationally is a core question for the design of immunoregulatory nanomaterials.

Two rare earths, erbium (Er) and dysprosium (Dy), can activate macrophages and improve phagocytosis capability and bioactivity for the increased presentation of antigens. The heterogeneity of two-dimensional nanosheets (2D NSs) comprehensively regulates immune functions of both Er (ROS-based mechanism) and Dy (NO-based mechanism), in comparison with either Er- or Dy-alone 2D NSs.

Because of their planar morphology, these 2D NSs target the mice lymph nodes without the use of any lymph node targeting functional molecules. Considering lymph nodes are a critical type of immunological tissue for mediating immune responses, the lymph node targeting capability of nanosheets effectively improve the efficacy of vaccines.

Figure 1. Characterization of rare-earth 2D NSs.

In regulating DNA vaccine-triggered immune responses, the 2D NSs simultaneously improve both humoral and cellular immune responses, compared to most other reported immunoregulators, which can only enhance either humoral or cellular responses. 2D NSs significantly improve the HIV-specific humoral response of IgG and the four subclasses (IgG1, IgG2a, IgG2b, and IgG3).

Furthermore, the 2D NSs can boost the enhancement of cytotoxic T lymphocytes to produce HIV-specific IFN-γ to neutralize HIV-infected cells. The balanced enhancement of HIV-specific humoral and cellular immune responses regulated by 2D NSs gives an unparalleled advantage for realizing the neutralization (mediated by humoral response) and cytotoxicity (cellular response) against HIV.

Figure 2. 2D NSs regulating HIV DNA vaccine-triggered immune responses

2D NSs-regulated HIV vaccine triggers six critical genes associated with various immunoregulation-related networks. The three natural killer cell lectin-like receptor subfamily genes Klrk1, Klrd1, and Klrc1, are triggered by nanosheets, which can effectively enhance the presentation of antigens. The 2D NSs induce the upregulation of the genes Ccr2 and Serpinb9 to regulate cytokine production. The 2D NSs are found to significantly up-regulate the expression of Msr1, a critical gene that activates the macrophages. The 2D NSs influences the immunoregulation-related network involving the activation of immune cells, antigen presentation, and the production of immune effectors to facilitate the HIV DNA vaccine to trigger stronger immune responses.

Figure 3. Transcriptome profiling of 2D NSs improving HIV DNA vaccine

In summary, the realization of the concept of 2D NSs immunoregulator dramatically broadens the choices to optimize the vaccination of infectious diseases, tumor immunotherapy, and other immune-based preventive treatment and therapy.

The Microfluidic-Biomaterials Lab at SUSTech is the corresponding author of this paper.

This work was supported by the National Natural Science Foundation of China (NSFC), the National Key R&D Program of China, the Chinese Academy of Sciences, Tencent Foundation through the XPLORER PRIZE, the Shenzhen Key Laboratory of Smart Healthcare Engineering, the Leading Medical Talents Program of Health Commission of Yunnan Province, the Young and Middle-Aged Academic and Technical Leaders Program of Yunnan Province, and the Basic Research Program of Yunnan Province.

Paper link: https://pubs.rsc.org/en/content/articlelanding/2022/SC/D1SC04044H