SPRm200 Surface Plasmon Resonance Microscopy is based on surface plasmon resonance (SPR) technology, which is the first biosensor  integrating optical microscopy with Surface Plasmon Resonance technology around the world.  SPRm200 can obtain cell in situ bright imaging、 SPR imaging、 SPR kinetic curve of quantitative affinity constant and binding dissociation constant and it opens a new frontier in the label-free study of molecule interaction. SPRm200 designed to label-free detect on cell membrane proteins and related molecule enables you not only not to extract or separate membrane proteins but also monitor the cell structure and measure the binding process of drug and target simultaneously.Meanwhile, SPRm200 can also measure the interaction of crude membrane proteins with drug and high resolution imaging can also be realized.Additionally, SPRm200 make it possible to realize the study of single or multiple cell, as a result, it can realize the heterogeneity of cell and drug binding and statistical analysis.  Due to its outstanding sensitivity and stability, SPRm200 can measure the binding behaviour in nanoscale, which can study the interaction of bacteria or virus with antibacterial drug and develop new nanoparticles delivered by drugs.

(1) Binding screening and analysis of micromolecule drug and single cell

(2) Binding screening of micromolecule drug（<200Da） and multiple  or living cells and precision statistical distribution analysis of single molecule, study on heterogeneity differences of cell

(3) Binding screening of antibody drug and multiple  or single cells and precision statistical distribution analysis of single molecule, study on heterogeneity differences of cell

(4) Interactions of bacteria or virus with antibacterial drug

Main function

Quantitative mapping of the interaction of living cell molecular in real time

Kinetic & quantitative analysis and statistical distribution of single or multiple cells

Bright field imaging、 SPR imaging combined with kinetic analysis in single point

Biomarker Monitoring, Drug target development

Label-free micromolecule analysis（<200Da）

Electrochemical  analysis

Micromolecule、DNA、antibody、peptide、protein、virus、bacteria、cell  

Technology features

Cell in situ: realize the in situ molecule interaction of cell level, not need to purify, in situ analyze the interaction of drug with molecule in cell level, especially provide solution to membrane proteins receptor (glycoprotein 、GPCR) and so on;

High flux: SPR field of  view is 600um*600um, so it can study the interaction of multiple cell and molecule simultaneously.As a result, it can realize the drug statistical analysis and cell heterogeneity study.

High precision: SPRm200 can realize the study on interaction of micromolecule(<200Da) with cells;

High resolution dynamic visualization: SPRm200 can  monitor the whole process and imaging of the interaction of drug molecule and cell in a dynamic and visualized way.In the meanwhile, it can obtain the quantitative SPR analysis  curve and obtain quantitative Ka，Kd ，KD. The high solution(1 um) imaging can realize single cell’s  solution imaging and quantitative data. 

3.Technology abilities

Study based on in situ cell molecule interaction

Micromolecule drug

   Among common drugs,  micromolecule drug represents 98% of the total. Micromolecule drug is usually a inhibitor delivering signal and it can specifically block the necessary signal conducting pathway in the process of tumor growth and proliferation and finally it can realize the aim of treatment. Micromolecule drug provides powder to be absorbed through concentration gradient.

1.Interaction of micromolecule with HEK 293 cell and GPR39 receptor

Fig.(a）SPR imaging，brightness and darkness reflect the degree of interaction among different cell and district ; Fig.(b）, bright imaging, can obtain the observation and district of different cell; Fig.(c）multiple interest district, SPR signal curve in every district, Fig(e,f,g) multiple interest district respectively,statistical distribution of  affinity constant/dissociation constant/biding constant:KD：413nM（42nM standard deviation），kd = 4.27E-3 s-1  (0.720E-3 standard deviation)，ka = 6.92E3 M-1 s-1  (0.721E3 standard deviation) 

2.Study on micromolecule and interaction of cell ASIC acid sensitive ionic pathway receptor

Antibody drug

Monoclonal antibody （mAb）therapy  has became a ripe method to treat cancer ,andautoimmune disease,  asthma and many other diseases.Monoclonal antibody （mAb）drug account for 50% of the whole biopharmacy , more than 60% of which are membrane protein receptors. SPRm200 allows quantitative studies of monoclonal antibody (mAb) and membrane protein binding at the single-cell level.Traditional SPR directly fixes the purified protein on the chip surface, which has problems in membrane proteins and it is difficult to extract from the cell environment and maintain their own structure.

Study based on interaction between virus and bacterial carrier molecules

1.Rapid ASTs experiment:study on metabolic activity of antibiotics and escherichia coli（Live E.Coli O157.H7）

ASTs is an important experiment to determine the antibiotic susceptibility and bacterial drug resistance.Currently, most AST experiments are based on cell culture and take several days to complete.Rapid AST detection can reduce morbidity and mortality and help develop early narrow-spectrum antibiotic therapy. Through SPRm200, we use plasma imaging and PIT technology to track the movement of individual bacterial cells and monitor  z-direction changes with cell metabolism and antibiotic inputs. As can be seen, antibiotics can significantly reduce the activity of bacterial cells and  be calculated quantitatively, thus becoming a fast AST detection method.

2.Study on interaction between different GPCR receptors and ligands based on SPRm200 and viral microarray

By electrochemical SPRM impedance analysis, the binding kinetic constants of viral peptide ligands and different GPCR receptors on the surface of the sensor were measured

Papers（Part）

[1] H Yu, X Shan, S Wang, N Tao, Achieving high spatial resolution surface plasmon resonance microscopy with image reconstruction, Anal. Chem., 2017, 89 (5), pp 2704–2707.

[2] Y Wang, X Shan, H Wang, S Wang, N Tao, Plasmonic imaging of surface electrochemical reactions of single gold nanowires, J. Am. Chem. Soc., 2017, 139 (4), pp 1376–1379.

[3] Dan Jiang, Yingyan Jiang, Zhimin Li, Tao Liu, Xiang Wo, Yimin Fang, Nongjian Tao, Wei Wang, Hong-Yuan Chen, Optical imaging of phase transition and Li-ion diffusion kinetics of single LiCoO2 nanoparticles during electrochemical cycling, J. Am. Chem. Soc., 2017, 139 (1), pp 186–192.

[4] Jin Lu, Yunze Yang, Wei Wang, Jinghong Li, Nongjian Tao, Shaopeng Wang, Label-free imaging of histamine mediated G protein-coupled receptors activation in live cells, Anal. Chem. 2016, 88, 11498−11503.

[5] Karan Syal, Rafael Iriya, Yunze Yang, Hui Yu, Shaopeng Wang, Shelley E Haydel, Hong-Yuan Chen, and Nongjian Tao, Antimicrobial Susceptibility Test with Plasmonic Imaging and Tracking of Single Bacterial Motions on Nanometer Scale, ACS Nano, 2016, 10(1), 845-852.

[6] Fenni Zhang, Shaopeng Wang, Linliang Yin, Yunze Yang, Yan Guan, Wei Wang, Han Xu and Nongjian Tao, Quantification of Epidermal Growth Factor Receptor Expression Level and Binding Kinetics on Cell Surfaces by Surface Plasmon Resonance Imaging, Anal. Chem. 2015, 87 (19), 9960-9965.

[7] Linliang Yin, Yunze Yang, Shaopeng Wang, Wei Wang, Shengtao Zhang, Nongjian Tao, Measuring the binding kinetics of antibody-conjugated gold nanoparticles with intact cells, Small, 11(31), 3782-3788.

[8] Yunze Yang,  Hui Yu,  Xiaonan Shan, Wei Wang, Xianwei Liu, Shaopeng Wang, and Nongjian Tao, Label-Free Tracking of Single Organelle Transportation in Cells with Nanometer Precision Using a Plasmonic Imaging Technique, Small, 11(24), 2878-2884, 2015

[8] Linliang Yin, Wei Wang, Shaopeng Wang, Fenni Zhang, Shengtao Zhang, Nongjian Tao, How does fluorescent labeling affect the binding kinetics of proteins with intact cells? Biosensors and Bioelectronics, 2015, 66, 412-416.

[9] Y Fang, S Chen, W Wang, X Shan, N Tao, Real-Time Monitoring of Phosphorylation Kinetics with Self-Assembled Nano-oscillators, Angewandte Chemie International Edition 2015, 54 (8), 2538-2542

[10] Karan Syal, Wei Wang, Xiaonan Shan, Shaopeng Wang, Hong-Yuan Chen, Nongjian Tao, Plasmonic imaging of protein interactions with single bacterial cells, Biosens. Bioelectron., 2015, 63, 131-137.

[11] Wei Wang, Linliang Yin, Laura Gonzalez-Malerva, Shaopeng Wang, Xiaobo Yu, Seron Eaton, Shengtao Zhang, Hong-Yuan Chen, Joshua LaBaer, Nongjian Tao, In situ drug-receptor binding kinetics in single cells: a quantitative label-free study of anti-tumor drug resistance, Scientific Reports, 2014, 4

[12] Hui Yu, Xiaonan Shan, Shaopeng Wang, Hong-Yuan Chen, Nongjian Tao, Molecular scale origin of surface plasmon resonance biosensors, Analytical Chemistry, 2014, 86 (18), 8992-8997.

[13] Xiaonan Shan, Yimin Fang, Shaopeng Wang, Yan Guan, Jongyuan Chen and Nongjian Tao, Detection of charges and molecules with self-assembled nano-oscillators, Nano Lett., 2014, 14 (7), 4151–4157.

[14] Hui Yu, Xiaonan Shan, Shaopeng Wang, Jongyuan Chen and Nongjian Tao, Plasmonic Imaging and Detection of Single DNA Molecules, ACS Nano, 2014, 8 (4), 3427–3433.

[15] Xiaonan Shan, Ismael Díez-Pérez, Luojia Wang, Peter Wiktor, Ying Gu, Lihua Zhang, Wei Wang, Jin Lu, Shaopeng Wang, Qihuang Gong, Jinghong Li & Nongjian Tao, Imaging the electrocatalytic activity of single nanoparticles, Nature Nanotechnology, 2012, 7, 668–672.

[16] Wei Wang, Yunze Yang, Shaopeng Wang, Vinay J Nagaraj, Qiang Liu, Jie Wu and Nongjian Tao, Label-free measuring and mapping of binding kinetics of membrane proteins in single living cells, Nature Chemistry, 2012, 4(10), 846-53.

[17] Wang, Wei; Wang, Shaopeng; Liu, Qiang; Wu, Jie; Tao, Nongjian, Mapping Single-Cell–Substrate Interactions by Surface Plasmon Resonance Microscopy, Langmuir, 2012, 28(37), 13373-13379.

[18] S. Wang, X. Shan, U. Patel, X. Huang, J. Lu, J. Li, NJ Tao, Label-free imaging, detection and mass measurement of single viruses by Surface Plasmon Resonance, Proc Natl Acad Sci U S A, 2010, 107 (37), 16028-16032