Research Progress----Shanghai Advanced Research Institute,Chinese Academy of Sciences

Scientists Reveal New Tools in Single-cell Infrared Microspectroscopy Based on Synchrotron Radiation

Single-cell technologies are becoming hot topics and key directions of biomedical research due to their abilities to answer the basic question of cellular functional heterogeneity and to interpret the molecular basis of various chronic diseases as well as aging. Among the single cell techniques, single-cell infrared spectroscopy obtains growing attention because of its advantages in simultaneously identifying the characteristics of intracellular metabolites. Recently, research team at Shanghai Advanced Research Institute together with collaborators have successfully revealed new tools to evaluate single-cell infrared data based on synchrotron radiation.

　　Single-cell technologies are becoming hot topics and key directions of biomedical research due to their abilities to answer the basic question of cellular functional heterogeneity and to interpret the molecular basis of various chronic diseases as well as aging. Among the single cell techniques, single-cell infrared spectroscopy obtains growing attention because of its advantages in simultaneously identifying the characteristics of intracellular metabolites.
　　Recently, Professor Lü Junhong’s group at Shanghai Advanced Research Institute (SARI), collaborating with Shanghai Center for Bioinformation Technology, National Engineering Research Center for Nanotechnology, Capital Medical University Tiantan Hospital, Binzhou Medical University and Shanghai Jiao Tong University Ruijin Hospital, have successfully revealed new tools to evaluate single-cell infrared data based on synchrotron radiation.
　　Fourier Transform infrared (FTIR) spectroscopy is a well-established non-destructive and sensitive analytical technique for the study of biological samples. Due to the inevitable technical errors/variation (caused by water vapor, CO2, instrument noise, etc.) or batch effects, a significant number of cells must be analyzed in order to distinguish the measured signal from controls with statistical confidence. Therefore, estimating a reasonable and practical amount for single-cell infrared spectroscopy is particularly necessary.
　　To this end, the group has developed a statistical method and procedure to evaluate single-cell spectral variability among two different cell types and two states. After calculating the similarity distance of the corresponding infrared spectra, they confirmed that 20 cells measured per time is sufficient to control batch effects (CV < 5%).
　　These findings provide a useful tool to evaluate the single-cell spectral quality and an important benchmark for the investigation of cellular heterogeneity.
　　Figure 1 Batch effects on single-cell infrared spectra and the establishment of evaluation methodology (Image adapted from Chemical Communications)
　　Cell phenomics is an emerging field that simultaneously characterizes many phenotypic traits of cells in response to genetic mutation and environmental influences. The group has proposed a label-free phenotypic screening strategy based on the combination of single-cell infrared microspectroscopy and the statistical calculations of the similarity among single cell infrared spectra.
　　This novel approach enables subtle phenotypic changes to be unveiled within individual cells by using comprehensive analysis of spectral similarity in chemical components. Based on this infrared phonemics method, they demonstrate for the first time phytomedicine protopanaxadiol with different concentration induces phenotypical changes of cancer cell HepG2.
　　These findings provide a powerful tool to accurately evaluate the cell stress responses and to largely expand the phenotypic screening toolkit for drug discovery.
　　Figure 2 Single-cell infrared phenomics and drug screening (Image adapted from Chemical Communications)
　　With the rapid technological advances, a variety of single-cell methods are emerging for the promise of unveiling cellular heterogeneity. The demand of a detailed and unbiased approach to simultaneously quantify global biomolecular structure information in a single cell and heterogeneity within cells is urgent.
　　The research group developed a novel strategy to quantitatively evaluate cellular heterogeneity based on single-cell synchrotron FTIR microspectroscopy and computational methods. After calculating the cell-to-cell similarity distance of the infrared spectral data, they confirmed that the statistical analysis of single-cell infrared phenotypes can be used to quantify the heterogeneity in a specific cell population. Based on this method, they revealed the infrared phenotypes have a similar tendency with increasing heterogenicity at the early stage and decreasing heterogenicity at the terminal stage of differentiation toward adipocyte lineage.
　　These findings provide an alternative methodology for dissecting the cellular heterogeneity, and the combination with other single-cell analysis tools will be very helpful for understanding the genotype-to-phenotype relationship in cellular populations.
　　Figure 3 Sing-cell infrared microspectroscopy quantifies dynamic heterogeneity of Mesenchymal stem cells during adipogenic differentiation (Image adapted from Analytical Chemistry)
　　These findings were published on Chemical Communications (2020,26:3773-3776;2020,86:13237-13240) and Analytical Chemistry (2020,10.1021/acs.analchem.0c04110) respectively.
　　These works were supported by the National Natural Science Foundation of China and from the BL01B beamline of the National Facility for Protein Science in Shanghai (NFPS) at Shanghai Synchrotron Radiation Facility.
　　Contact: Lü Junhong
　　Shanghai Advanced Research Institute, Chinese Academy of Sciences
　　Email: lujunhong@zjlab.org.cn

2021-01-05 more+

Novel compound/c-Si passivation contact for p‐Type Crystalline Silicon Solar Cells Achieving 20% Efficiency

Crystalline silicon heterojunction solar cells based on hole-selective MoOX contacts provide obvious merits in terms of the decent passivation and carrier selectivity but face the challenge of long-term stability. With the aim to improve the performance and stability of solar cells with full area MoOX/ metal contacts, a SiOX tunneling layer on silicon surface is intentionally formed by UV/O3 treatment and an indium tin oxide (ITO) film is sputtered as a high-work-function electrode.

　　Efficient separation and collection of photogenerated carriers through the formation of asymmetric electron and hole transport channels is one of the central issues for crystalline silicon (c-Si) solar cells and other types of photovoltaic devices. Silicon heterojunction solar cells based on MoOX (X<3) hole-selective contacts show significant advantages in carrier-selective transport, however, it faces the challenge for long-term stability due to poor thermodynamic stability of MoOX.
　　Motivated by such a challenge, a research team led by Prof. LI Dongdong at Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences collaborated with Jinneng Clean Energy Technology Limited reported a novel stacked structure (c-Si/SiOX/MoOX/V2OX/ITO/Ag) to improve the stability of c-Si solar cells. The research results were published in Advanced Functional Materials entitled “Stable MoOX‐Based Heterocontacts for p‐Type Crystalline Silicon Solar Cells Achieving 20% Efficiency”.
　　In this work, the research team introduced a SiO2 tunneling passivation layer at the MoOX/c-Si interface to suppress the redox reaction brought about by the direct contact between MoOX and c-Si, which keeps the work function of MoOX at a relatively high level. An ultra-thin V2OX layer is deposited on the surface of MoOX film to improve the stability of the heterojunction structure in air and its resistance to sputtering damage. At the same time, the ITO layer is fabricated at the V2OX/Ag interface, which effectively inhibits the migration of metal ion, and finally constructs a tandem structure of c-Si/SiOX/MoOX/V2OX/ITO/Ag, with power conversion efficiency (PCE) of 20.0% and significantly improved stability.
　　This work innovatively constructs a stacked thin film structure based on an in-depth understanding of the interfacial evolution of MoOX/c-Si and MoOX/metal electrodes, providing a new approach to the study of compound/c-Si passivated contact heterojunction solar cells, which can be extended as a universal method to improve the efficiency and stability of heterojunction solar cells and other types of optoelectronics.
　　This work was supported by the National Natural Science Foundation of China, the Natural Science Foundation of Shanghai, the Shanxi Science and Technology Department, and the Youthnnovation Promotion Association of the Chinese Academy of Sciences.
　　
　　Figure 1. The device performances as a function of UV/O3 pre-treatment (Image adapted from Advanced Functional Materials)
　　Figure 2. Characterizations of XPS spectra and passivation properties of MoOX films (Image adapted from Advanced Functional Materials)
　　Contact: LI Dongdong
　　Shanghai Advanced Research Institute, Chinese Academy of Sciences
　　Email: lidd@sari.ac.cn
　　

2020-09-22 more+

Researchers Develop Integrative Treatment of Tumor-related Bone Defects

Malignant bone tumors have caused great obstacles and serious illnesses for tumor recurrence and difficulty in reconstructing and repairing large defeats after tumorectomy due to the poor prognosis for metastatic relapse or recurrence for patients with the axial disease. In a study published in Chemical Engineering Journal, a research team from the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences (CAS) reported a novel therapeutic treatment of anti-tumor/bone repair by combination of MoS2 nanosheets with 3D printed bioactive borosilicate glass scaffolds.

　　Malignant bone tumors have caused great obstacles and serious illnesses for tumor recurrence and difficulty in reconstructing and repairing large defeats after tumorectomy due to the poor prognosis for metastatic relapse or recurrence for patients with the axial disease.
　　In a study published in Chemical Engineering Journal, a research team led by Prof. LI Jiusheng from the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences (CAS), collaborated with Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shenzhen University, etc. reported a novel therapeutic treatment of anti-tumor/bone repair by combination of MoS2 nanosheets with 3D printed bioactive borosilicate glass scaffolds.
　　Based on the proof of concept of “integrative treatment”, scientists reported for the first time on the concept of “integrative treatment” on local combating tumor and bone tissue repairing by integrating anti-tumor/bone repair functions together by fixing MoS2 on the surface of materials. The material’s properties, bioactive ability, photothermal stability and capability, osteogenesis and the anti-tumor ability of BGM composite scaffolds in vitro and vivo were later evaluated and investigated in this study.
　　The MoS2-integrated composite BG (BGM) scaffolds can rapidly and effectively elevate temperature, and they exhibited excellent photothermal stability. Notably, the BGM scaffolds can effectively reduce the viability of osteosarcoma cells (MNNG/HOS) in vitro as well as inhibit the tumor growth in nude mice. Furthermore, the prepared BGM scaffolds can stimulate the proliferation and differentiation of rat bone mesenchymal stem cells (rBMSCs), upregulate the expression of osteogenesis-related genes in vitro and promote in vivo bone repair in critical-sized rat calvarial defects.
　　Therefore, the “integrative treatment” BGM scaffolds have great potential to be applied in the treatment of anti-tumor and bone repair, offering ideas for the manufacture of new materials in the tissue engineering field.
　　Schematic diagram for investigation on the integrative treatment of anti-tumor/bone repairing with 3D printing BGM scaffolds (Image by SARI)
　　The study was supported by the National Natural Science Foundation, China (Grant Nos. 51802326) and Youth innovation promotion association of Chinese Academy of Sciences (Grant No. 2020292).
　　Contact: Wang Hui
　　Shanghai Advanced Research Institute, Chinese Academy of Sciences
　　Email: wanghui01@sari.ac.cn

2020-07-17 more+

New Light-based Method Proposed for C(sp3)–H Functionalizations of Light Hydrocarbons

Intrinsic inertness of gaseous hydrocarbons requires harsh reaction conditions to enable C(sp3)–H bond cleavage, resulting in low-yielding and unselective transformation to high-value added chemicals. Motivated by such a challenge, a team collaborated by researchers from Eindhoven University of Technology, ShanghaiTech University and Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences reported a general and mild strategy to directly activate alkanes using decatungstate photocatalysis in flow.

　　Intrinsic inertness of gaseous hydrocarbons (e.g., ethane and methane) requires harsh reaction conditions to enable C(sp3)–H bond cleavage, resulting in low-yielding and unselective transformation to high-value added chemicals. Therefore, direct activation of gaseous hydrocarbons remains a major challenge for the chemistry community.
　　Motivated by such a challenge, a team collaborated by researchers from Eindhoven University of Technology, ShanghaiTech University and Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences reported a general and mild strategy to directly activate alkanes using decatungstate photocatalysis in flow. The study was published in the latest issue of Science on July 3.
　　The newly developed method aims to irradiate the molecules with light in the presence of a suitable catalyst, thereby immediately converting low-weight hydrocarbons into more complex molecules at room temperature and low pressure. To achieve that, researchers had to address the following challenges: first, the cleavage of very strong aliphatic C–H bonds with a bond dissociation energy (BDE) between 96.5 and 105 kcal mol-1 (Figure 1B) and second, appropriate technologies to bring the alkanes and catalyst into close proximity with a suitable catalyst and reaction partner.
　　Given the photoexcited decatungstateanion (W10O324-) has enabled a number of synthetically useful C(sp3)–H functionalizations, scientists reasoned that the use of flow technology is indispensable to facilitate the gas-liquid decatungstate-mediated processes. Through investigation to optimize reaction conditions and transformation scope, scientists solved these two problems by exciting the alkanes with UV light (about 365 nm) in the presence of a suitable catalyst tetrabutylammonium decatungstate (TBADT) in flow.
　　This new method paves the way for the inexpensive production of some medicines, in view of the low cost of catalysts to activate the gaseous alkanes and simplification of reactions. Further research is needed to apply intensified reactors to increase production capacity.
　　Fig. 1 Decatungstate enables the direct C(sp3)–H activation of light hydrocarbons. (Image adapted from Science)
　　Contact: SUN Yuhan
　　Shanghai Advanced Research Institute, Chinese Academy of Sciences
　　Email: sunyh@sari.ac.cn

2020-07-10 more+

NOW OPEN: The expression plasmids for all 29 proteins encoded by the COVID-19 virus are available for request

Now, expression plasmids for all these 29 proteins are available to global scientists through a Protein Bank Program (PBP) launched by the National Facility for Protein Science in Shanghai (NFPS).

2020-06-22 more+

Efficient Indium Oxide Catalysts Designed for CO2 Hydrogenation to Methanol

Catalytic hydrogenation of carbon dioxide is a green and sustainable means of synthesizing commodity chemicals such as methanol.Recent studies revealed the potential for a family of metal oxides to catalyze this reaction. However, further optimizing their catalytic performance for industrial applications remained a great challenge.A team at the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences reported a successful case of theory-guided rational design of indium oxide (In2O3) catalysts for CO2 hydrogenation to methanol with high activity and selectivity.

　　Catalytic hydrogenation of carbon dioxide (CO2) is a green and sustainable means of synthesizing commodity chemicals such as methanol. This conversion process is key to realizing the “methanol economy” or creating “liquid sunshine,” both aspects of the circular economy. Recent studies revealed the potential for a family of metal oxides to catalyze this reaction. However, further optimizing their catalytic performance for industrial applications remained a great challenge, mostly due to the difficulties related to the rational design and controlled synthesis of these catalysts.
　　Motivated by such a challenge, a team jointly led by Profs. SUN Yuhan, GAO Peng, and LI Shenggang at the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences, reported a successful case of theory-guided rational design of indium oxide (In2O3) catalysts for CO2 hydrogenation to methanol with high activity and selectivity. The new findings were published in the latest issue of Science Advances on June 17.
　　To rationally design In2O3-based nanocatalysts with favorable methanol synthesis performance, researchers carried out extensive density functional theory (DFT) calculations to establish the catalytic mechanism of the In2O3 catalyst during CO2 hydrogenation to methanol and carbon dioxide by identifying preferred pathways. The computational modeling identified the rarely studied {104} facet of hexagonal In2O3 as the most favorable for methanol synthesis.
　　On the basis of this theoretical prediction, several experimental methods were then employed to synthesize In2O3 catalysts in different phases with distinct morphologies.
　　Interestingly, one of the four In2O3 catalysts synthesized in this way was confirmed to mainly expose the theoretically identified {104} facets. This catalyst also exhibited the best performance in terms of both activity and selectivity, confirming the DFT prediction. The methanol synthesis reaction catalyzed by this catalyst is favorable even at the very high temperature of 360 °C.
　　The space-time yield of methanol reached 10.9 mmol/g/hour at this temperature, which surpassed all previously known catalysts for this reaction, including previously reported In2O3-based catalysts and well-known Cu-based catalysts.
　　The In2O3 catalyst discovered in this research is promising as a way to directly convert CO2 into methanol for industrial applications. In addition, the discovery of this In2O3 catalyst will promote the further development of oxide/zeolite bifunctional catalysts for direct CO2 hydrogenation to various C2+ hydrocarbons (lower olefins, gasoline, aromatics and so on) via the methanol intermediate. Just as importantly, this discovery also highlights the pivotal role of computational science in helping to design industrially relevant catalysts.
　　 Schematic illustration of the most favorable CO2 hydrogenation pathways on different cubic (c–In2O3) and hexagonal indium oxide (c–In2O3) surfaces (Figures adapted from Science Advances)
　　
　　 Structural characterization and catalytic performance of various In2O3 catalyst materials for CO2 hydrogenation (Figures adapted from Science Advances)
　　

2020-06-18 more+