Co-reporter:Tingting Zheng, Enduo Feng, Zhiqiang Wang, Xueqing Gong, and Yang Tian
ACS Applied Materials & Interfaces October 25, 2017 Volume 9(Issue 42) pp:36596-36596
Publication Date(Web):October 5, 2017
DOI:10.1021/acsami.7b11028
With a burst development of new nanomaterials for plasmon-free surface-enhanced Raman scattering (SERS), the understanding of chemical mechanism (CM) and further applications have become more and more attractive. Herein, a novel SERS platform was specially designed through electrochemical deposition of graphene onto TiO2 nanoarrays (EG–TiO2). The developed EG–TiO2 nanocomposite SERS platform possessed remarkable Raman activity using copper phthalocyanine (CuPc) as a probe molecule. X-ray photoelectron spectroscopy measurement revealed that the chemical bond Ti–O–C was formed at the interface between graphene and TiO2 in EG–TiO2 nanocomposites. Both experimental and theoretical results demonstrated that the obvious Raman enhancement was attributed to TiO2-induced Fermi level shift of graphene, resulting in effective charge transfer between EG–TiO2 nanocomposites and molecules. Taking advantage of a marked Raman response of the CuPc molecule on the EG–TiO2 nanocomposite surface as well as specific recognition of CuPc toward multiple telomeric G-quadruplex, EG–TiO2 nanocomposites were tactfully employed as the SERS substrate for selective and ultrasensitive determination of telomerase activity, with a low detection limit down to 2.07 × 10–16 IU. Interestingly, the self-cleaning characteristic of EG–TiO2 nanocomposites under visible light irradiation successfully provided a recycling ability for this plasmon-free EG–TiO2 substrate. The present SERS biosensor with high analytical performance, such as high selectivity and sensitivity, has been further explored to determine telomerase activity in stem cells as well as to count the cell numbers. More importantly, using this useful tool, it was discovered that telomerase activity plays an important role in the proliferation and differentiation from human mesenchymal stem cells to neural stem cells. This work has not only established an approach for gaining fundamental insights into the chemical mechanism (CM) of Raman enhancement but also has opened a new way in the investigation of long-term dynamics of stem cell differentiation and clinical drug screening.Keywords: graphene; stem cells; surface-enhanced Raman scattering; telomerase activity; TiO2;
Co-reporter:Shuai Li, Anwei Zhu, Tong Zhu, John Z. H. Zhang, and Yang Tian
Analytical Chemistry June 20, 2017 Volume 89(Issue 12) pp:6656-6656
Publication Date(Web):May 31, 2017
DOI:10.1021/acs.analchem.7b00881
Glucose and pH are two important indicators of diabetes mellitus. However, their dynamic changes at the same time in brain are still not clear, mainly due to a lack of a single biosensor capable of simultaneous quantification of two species in a live rat brain. In this work, a selective and sensitive ratiometric electrochemical biosensor was developed for simultaneously quantifying glucose and pH using both current and potential outputs in a rat brain of diabetic model. Here, glucose oxidase was first employed as a specific recognition element for both glucose and pH because the active center (FAD) could undergo a 2H+/2e– process. Moreover, an insensitive molecule toward pH and glucose was used as an inner-reference element to provide a built-in correction to improve the accuracy. The ratio between the oxidation peak current density of glucose and that of ABTS gradually increased with increasing concentration of glucose, and showed a good linearity in the range of 0.3–8.2 mM. Meanwhile, the midpotential difference between glucose oxidase and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) positively shifted with pH decreasing, leading to accurate determination of pH in the linear range of 5.67–7.65. Thus, combined with the unique properties of carbon fiber microelectrode, including easy to insert and good biocompatibility, the developed single biosensor was successfully applied to detect pH and glucose at the same time in hippocampus, striatum, and cortex in a live rat brain of diabetic model.
Co-reporter:Wanying Li;Bingqing Fang;Ming Jin
Analytical Chemistry February 21, 2017 Volume 89(Issue 4) pp:2553-2560
Publication Date(Web):January 24, 2017
DOI:10.1021/acs.analchem.6b04781
Zinc ion (Zn2+) not only plays an important function in the structural, catalytic, transcription, and regulatory of proteins, but is also an essential ionic signal to regulate brain neurotransmitters pass process. In this work, we designed and synthesized an intramolecular charge transfer-based ratiometric two-photon fluorescence probe, P–Zn, for imaging and biosensing of Zn2+ in live cell, hippocampal tissue, and zebrafish. The developed probe demonstrated high two-photon absorption cross section (δ) of 516 ± 77 GM, which increased to 958 ± 144 GM after the probe was coordinated with Zn2+. Furthermore, this P–Zn probe quickly recognized Zn2+ with high selectivity, over other metal ions, amino acids, and reactive oxygen species. More interestingly, the initial emission peak of the present probe at 465 nm decreased with a new peak increased at 550 nm, leading to the ratiometric determination of Zn2+ with high accuracy. Finally, this two-photon fluorescence probe with high temporal resolution and remarkable analytical performance, as well as low-cytotoxicity, was successfully applied in imaging of live cells, hippocampal tissues, and zebrafishes. The present P–Zn probe combined with FLIM provided accurate mapping of Zn2+ distribution at single-cell level. More interestingly, the two-photon spectroscopic results demonstrated that the level of Zn2+ in hippocampal tissue of mouse with AD was higher than that in normal mouse brain.
Co-reporter:Hui Dong, Limin ZhangWei Liu, Yang Tian
ACS Chemical Neuroscience 2017 Volume 8(Issue 2) pp:
Publication Date(Web):December 6, 2016
DOI:10.1021/acschemneuro.6b00296
The potential damage of Alzheimer’s disease (AD) in brain function has attracted extensive attention. As the most common anion, Cl– has been indicated to play significant roles in brain diseases, particularly in the pathological process of AD. In this work, a label-free selective and accurate electrochemical biosensor was first developed for real-time monitoring of Cl– levels in a mouse brain model of AD and rat brain upon global cerebral ischemia. Silver nanoparticles (AgNPs) were designed and synthesized as selective recognition element for Cl–, while 5′-MB-GGCGCGATTTT-SH-3′ (SH-DNA-MB, MB = methylene blue) was selected as an inner reference molecule for a built-in correction to avoid the effects from the complicated brain. The electrochemical biosensor showed high accuracy and remarkable selectivity for determination of Cl– over other anions, metal ions, amino acids, and other biomolecules. Furthermore, three-dimensional nanostructures composed of single-walled carbon nanotubes (SWNTs) and Au nanoleaves were assembled on the carbon fiber microelectrode (CFME) surface to enhance the response signal. Finally, the developed biosensor with high analytical performance, as well as the unique characteristic of CFME itself including inertness in live brain and good biocompatibility, was successfully applied to in vivo determination of Cl– levels in three brain regions: striatum, hippocampus, and cortex of live mouse and rat brains. The comparison of average levels of Cl– in normal striatum, hippocampus, and cortex of normal mouse brains and those in the mouse model brains of AD was reported. In addition, the results in rat brains followed by cerebral ischemia demonstrated that the concentrations of Cl– decreased by 19.8 ± 0.5% (n = 5) in the striatum and 27.2 ± 0.3% (n = 5) in hippocampus after cerebral ischemia for 30 min, but that negligible change in Cl– concentration was observed in cortex.Keywords: Alzheimer’s disease; cerebral ischemia; Chloride ion; electrochemical biosensors; silver nanoparticles;
Co-reporter:Limin Zhang, Fangling Liu, Xuemei Sun, Guang-feng Wei, Yang TianZhi-pan Liu, Rong Huang, Yanyan Yu, Huisheng Peng
Analytical Chemistry 2017 Volume 89(Issue 3) pp:
Publication Date(Web):January 5, 2017
DOI:10.1021/acs.analchem.6b04168
Ascorbic acid (AA) levels are closely correlated with physiological and pathological events in brain diseases, but the mechanism remains unclear, mainly due to the difficulty of accurately analyzing AA levels in live brain. In this study, by engineering tunable defects and oxygen-containing species in carbon nanotubes, a novel aligned carbon nanotube fiber was developed as an accurate microsensor for the ratiometric detection of AA levels in live rat brains with Alzheimer’s disease (AD). AA oxidation is greatly facilitated on the fiber surface at a low potential, leading to high sensitivity as well as high selectivity against potential sources of interference in the brain. Additionally, an unexpected, separate peak from the fiber surface remains constant as the AA concentration increases, enabling real-time and ratiometric detection with high accuracy. The results demonstrated that the AA levels were estimated to be 259 ± 6 μM in cortex, 264 ± 20 μM in striatum, and 261 ± 21 μM in hippocampus, respectively, in normal condition. However, the overall AA level was decreased to 210 ± 30 μM in cortex, 182 ± 5 μM in striatum, and 136 ± 20 μM in hippocampus in the rat brain model of AD. To the best of our knowledge, this work is the first to accurately detect AA concentrations in the brains of live animal model of AD.
Co-reporter:Qiao Xu;Wei Liu;Li Li;Feng Zhou;Jian Zhou
Chemical Communications 2017 vol. 53(Issue 11) pp:1880-1883
Publication Date(Web):2017/02/02
DOI:10.1039/C6CC09563A
Herein, a ratiometric SERS probe was created for monitoring nitric oxide (NO) by designing a novel molecule, 3,4-diaminobenzene-thiol, and immobilizing this molecule onto trisoctahedral gold nanostructures with superior SERS capability. The established probe possessed good selectivity and biocompatibility, high sensitivity and accuracy, thus enabling imaging and biosensing of NO in live cells.
Co-reporter:Dr. Wei Liu;Hui Dong;Dr. Limin Zhang; Yang Tian
Angewandte Chemie 2017 Volume 129(Issue 51) pp:16546-16550
Publication Date(Web):2017/12/18
DOI:10.1002/ange.201710863
AbstractAn efficient biosensor was created for the ratiometric monitoring of Cu+ and pH in the brain using both current and potential outputs. A series of N,N-bis(2-[2-(ethylthio)ethyl])-based (NS4s) derivatives was designed for the specific recognition of Cu+. After systematically evaluating the electrochemical parameters of Cu+ oxidation by tuning alkyl chain length, polyaromatic structure, and substitute group site of NS4, N,N-bis(2-[2-(ethylthio)ethyl])-2-naphthamide (NS4-C1) was finally optimized for Cu+ detection as it showed the most negative potential and the largest current density. At the same time, 9,10-anthraquinone was used as a selective pH sensor with 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) as an internal reference. This single biosensor with both current and potential signal outputs can simultaneously determine Cu+ concentrations from 0.5 to 9.5 μm and pH values ranging from 6.0 to 8.0. The efficient biosensor was applied to the simultaneous detection of Cu+ and pH in the live brain. The average levels of Cu+ were reported for the first time in the cortex, hippocampus, and striatum in a mouse model of Alzheimer's disease.
Co-reporter:Dr. Wei Liu;Hui Dong;Dr. Limin Zhang; Yang Tian
Angewandte Chemie International Edition 2017 Volume 56(Issue 51) pp:16328-16332
Publication Date(Web):2017/12/18
DOI:10.1002/anie.201710863
AbstractAn efficient biosensor was created for the ratiometric monitoring of Cu+ and pH in the brain using both current and potential outputs. A series of N,N-bis(2-[2-(ethylthio)ethyl])-based (NS4s) derivatives was designed for the specific recognition of Cu+. After systematically evaluating the electrochemical parameters of Cu+ oxidation by tuning alkyl chain length, polyaromatic structure, and substitute group site of NS4, N,N-bis(2-[2-(ethylthio)ethyl])-2-naphthamide (NS4-C1) was finally optimized for Cu+ detection as it showed the most negative potential and the largest current density. At the same time, 9,10-anthraquinone was used as a selective pH sensor with 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) as an internal reference. This single biosensor with both current and potential signal outputs can simultaneously determine Cu+ concentrations from 0.5 to 9.5 μm and pH values ranging from 6.0 to 8.0. The efficient biosensor was applied to the simultaneous detection of Cu+ and pH in the live brain. The average levels of Cu+ were reported for the first time in the cortex, hippocampus, and striatum in a mouse model of Alzheimer's disease.
Co-reporter:Li Liu;Fan Zhao;Dr. Wei Liu;Tong Zhu; John Z. H. Zhang;Chen Chen; Zhihui Dai; Huisheng Peng;Jun-Long Huang;Dr. Qin Hu; Wenbo Bu; Yang Tian
Angewandte Chemie International Edition 2017 Volume 56(Issue 35) pp:10471-10475
Publication Date(Web):2017/08/21
DOI:10.1002/anie.201705615
AbstractHerein, we develop a novel method for designing electrochemical biosensors with both current and potential signal outputs for the simultaneous determination of two species in a living system. Oxygen (O2) and pH, simple and very important species, are employed as model molecules. By designing and synthesizing a new molecule, Hemin-aminoferrocene (Hemin-Fc), we create a single electrochemical biosensor for simultaneous detection and ratiometric quantification of O2 and pH in the brain. The reduction peak current of the hemin group increases with the concentration of O2 from 1.3 to 200.6 μm. Meanwhile, the peak potential positively shifts with decreasing pH from 8.0 to 5.5, resulting in the simultaneous determination of O2 and pH. The Fc group can serve as an internal reference for ratiometric biosensing because its current and potential signals remain almost constant with variations of O2 and pH. The developed biosensor has high temporal and spatial resolutions, as well as remarkable selectivity and accuracy, and is successfully applied in the real-time quantification of O2 and pH in the brain upon ischemia, as well as in tumor during cancer therapy.
Co-reporter:Dazhi Yao;Wenqi Zhao;Limin Zhang
Analyst (1876-Present) 2017 vol. 142(Issue 22) pp:4215-4220
Publication Date(Web):2017/11/06
DOI:10.1039/C7AN01295K
Developing a sensitive and accurate method for Furin activity is still the bottleneck for understanding the role played by Furin in cell-surface systems and even in Alzheimer's disease. In this work, a ratiometric electrochemical biosensor was developed for sensitive and accurate determination of Furin activity in the cell based on dual signal amplification stemming from a peptide with multiple response sites and the antifouling gold nano-bellflowers (GBFs). A new peptide, HS-CMRVRR↓YKDFDFG (P3), was designed for the first time to be selectively cleaved by Furin at site↓. More importantly, this peptide P3 constitutes three amino acid residues with the –COOH group subsequently used to bind with the response molecule of ferrocene, and can remarkably improve the determination sensitivity by about 2.3 fold. Meanwhile, GBFs stabilized by PEG were taken as a second element to magnify the signal of the ferrocene group via a large ratio surface area and good conductivity, as well as an antibiofouling nanosurface to reduce the biofouling of the electrode surface in cells. This double amplification strategy can greatly enhance the sensitivity of Furin detection by 6.5-fold, which is favorable for detection of low amounts of Furin. In addition, 5′-MB-GGCGCGA(T)13-SH-3′ was co-assembled as an inner reference to provide a built-in element to correct the determination error resulting from a complicated analysis environment. Finally, this sensitive and accurate Furin biosensor was successfully applied to detect Furin activity in Furin overexpressed U251 and MDA-MB-468 cells. As far as we know, this is the first report to mention an electrochemical strategy to detect Furin activity in cells.
Co-reporter:Li Liu;Fan Zhao;Dr. Wei Liu;Tong Zhu; John Z. H. Zhang;Chen Chen; Zhihui Dai; Huisheng Peng;Jun-Long Huang;Dr. Qin Hu; Wenbo Bu; Yang Tian
Angewandte Chemie 2017 Volume 129(Issue 35) pp:10607-10611
Publication Date(Web):2017/08/21
DOI:10.1002/ange.201705615
AbstractHerein, we develop a novel method for designing electrochemical biosensors with both current and potential signal outputs for the simultaneous determination of two species in a living system. Oxygen (O2) and pH, simple and very important species, are employed as model molecules. By designing and synthesizing a new molecule, Hemin-aminoferrocene (Hemin-Fc), we create a single electrochemical biosensor for simultaneous detection and ratiometric quantification of O2 and pH in the brain. The reduction peak current of the hemin group increases with the concentration of O2 from 1.3 to 200.6 μm. Meanwhile, the peak potential positively shifts with decreasing pH from 8.0 to 5.5, resulting in the simultaneous determination of O2 and pH. The Fc group can serve as an internal reference for ratiometric biosensing because its current and potential signals remain almost constant with variations of O2 and pH. The developed biosensor has high temporal and spatial resolutions, as well as remarkable selectivity and accuracy, and is successfully applied in the real-time quantification of O2 and pH in the brain upon ischemia, as well as in tumor during cancer therapy.
Co-reporter:Rongli Ma;Ming Jin
Journal of Analysis and Testing 2017 Volume 1( Issue 2) pp:11
Publication Date(Web):16 May 2017
DOI:10.1007/s41664-017-0011-y
New methods are desired not only to quantitatively determine but also effectively remove mercury from environmental sources, because mercury is a highly hazardous and ubiquitous pollutant with bioaccumulative properties. Herein, we developed an ultrasensitive and highly selective ratiometric electrochemical probe for accurate determination and quick removal of mercury from water. Phenyl thiourea (PT) was designed as a specific recognition element for Hg2+, and detection was achieved by selective binding and reduction of Hg2+ on PT-functionalized electrode. Meanwhile, HS-DNA-MB (5′-MB-AGGAGGAGGAGGGAGGAGGG-SH-3′) was designed as an inner reference element, providing a built-in correction for quantitative determination of Hg2+. The present probe shows high sensitivity for Hg2+ detection in a broad dynamic range from 1 nM to 1.3 μM, with relatively low detection limit of 0.12 nM (0.024 ppb). This electrochemical probe was successfully applied for determination of Hg2+ in environmental water. More interestingly, it was also used to effectively remove Hg2+ from Huangpu River water within just 7 min without further separation.
Co-reporter:Fan Zhao, Limin Zhang, Anwei Zhu, Guoyue Shi and Yang Tian
Chemical Communications 2016 vol. 52(Issue 18) pp:3717-3720
Publication Date(Web):25 Jan 2016
DOI:10.1039/C5CC09540A
pH plays an important role in the biochemical, ion-regulatory, or electrical machinery of nerve and glial cells, and is considered to be related to a number of degenerative diseases. Herein, we first develop a two-channel electrochemical ratiometric biosensor for local pH determination in a live rat brain, and report the accurate pH values in the different regions of live brains upon global cerebral ischemia.
Co-reporter:Weikang Wang, Limin Zhang, Li Li, and Yang Tian
Analytical Chemistry 2016 Volume 88(Issue 19) pp:9518
Publication Date(Web):September 6, 2016
DOI:10.1021/acs.analchem.6b02081
Hypochlorite (ClO–) and glutathione (GSH) have been reported to closely correlate with oxidative stress and related diseases; however, a clear mechanism is still unknown, mainly owing to a lack of accurate analytical methods for live cells. Herein we create a novel surface-enhanced Raman scattering (SERS) nanoprobe, 4-mercaptophenol (4-MP)-functionalized gold flowers (AuF/MP), for imaging and biosensing of ClO– and GSH in RAW 264.7 macrophage cells upon oxidative stress. The SERS spectra of AuF/MP change with the reaction between ClO– and 4-MP on AuFs within 1 min and then recover after reaction with GSH, resulting in the ratiometric detection of ClO– and GSH with high accuracy. The single SERS probe also shows high selectivity for ClO– and GSH detection against other reactive oxygen species and amino acids which may exist in biological systems, as well as remarkable sensitivity ascribed to a larger amount of hot spots on AuFs. The significant analytical performance of the developed nanoprobe, together with good biocompatibility and high cell-permeability, enables the present SERS probe imaging and real-time detection of ClO– and GSH in live cells upon oxidative stress.
Co-reporter:Jie Zhou, Limin Zhang, and Yang Tian
Analytical Chemistry 2016 Volume 88(Issue 4) pp:2113
Publication Date(Web):January 15, 2016
DOI:10.1021/acs.analchem.5b03634
To develop in vivo monitoring meter for pH measurements is still the bottleneck for understanding the role of pH plays in the brain diseases. In this work, a selective and sensitive electrochemical pH meter was developed for real-time ratiometric monitoring of pH in different regions of rat brains upon ischemia. First, 1,2-naphthoquinone (1,2-NQ) was employed and optimized as a selective pH recognition element to establish a 2H+/2e– approach over a wide range of pH from 5.8 to 8.0. The pH meter demonstrated remarkable selectivity toward pH detection against metal ions, amino acids, reactive oxygen species, and other biological species in the brain. Meanwhile, an inner reference, 6-(ferrocenyl)hexanethiol (FcHT), was selected as a built-in correction to avoid the environmental effect through coimmobilization with 1,2-NQ. In addition, three-dimensional gold nanoleaves were electrodeposited onto the electrode surface to amplify the signal by ∼4.0-fold and the measurement was achieved down to 0.07 pH. Finally, combined with the microelectrode technique, the microelectrochemical pH meter was directly implanted into brain regions including the striatum, hippocampus, and cortex and successfully applied in real-time monitoring of pH values in these regions of brain followed by global cerebral ischemia. The results demonstrated that pH values were estimated to 7.21 ± 0.05, 7.13 ± 0.09, and 7.27 ± 0.06 in the striatum, hippocampus, and cortex in the rat brains, respectively, in normal conditions. However, pH decreased to 6.75 ± 0.07 and 6.52 ± 0.03 in the striatum and hippocampus, upon global cerebral ischemia, while a negligible pH change was obtained in the cortex.
Co-reporter:Jingni Fu, Changqin Ding, Anwei Zhu and Yang Tian
Analyst 2016 vol. 141(Issue 15) pp:4766-4771
Publication Date(Web):31 May 2016
DOI:10.1039/C6AN00981F
Intracellular pH plays a vital role in cell biology, including signal transduction, ion transport and homeostasis. Herein, a ratiometric fluorescent silica probe was developed to detect intracellular pH values. The pH sensitive dye fluorescein isothiocyanate isomer I (FITC), emitting green fluorescence, was hybridized with reference dye rhodamine B (RB), emitting red fluorescence, as a dual-emission fluorophore, in which RB was embedded in a silica core of ∼40 nm diameter. Moreover, to prevent fluorescence resonance energy transfer between FITC and RB, FITC was grafted onto the surface of core–shell silica colloidal particles with a shell thickness of 10–12 nm. The nanoprobe exhibited dual emission bands centered at 517 and 570 nm, under single wavelength excitation of 488 nm. RB encapsulated in silica was inert to pH change and only served as reference signals for providing built-in correction to avoid environmental effects. Moreover, FITC (λem = 517 nm) showed high selectivity toward H+ against metal ions and amino acids, leading to fluorescence variation upon pH change. Consequently, variations of the two fluorescence intensities (Fgreen/Fred) resulted in a ratiometric pH fluorescent sensor. The specific nanoprobe showed good linearity with pH variation in the range of 6.0–7.8. It can be noted that the fluorescent silica probe demonstrated good water dispersibility, high stability and low cytotoxicity. Accordingly, imaging and biosensing of pH variation was successfully achieved in HeLa cells.
Co-reporter:Feifei Cao, Limin Zhang, Yang Tian
Journal of Electroanalytical Chemistry 2016 Volume 781() pp:278-283
Publication Date(Web):15 November 2016
DOI:10.1016/j.jelechem.2016.10.027
Selective and reliable method is of great importance for in vivo analysis in the complicated brain. In this work, we developed a new approach for detection of ascorbic acid (AA) based on a new nitrogen-doped nanotube fiber (NCNF) microelectrode. After electrochemical pre-treatment, the NCNF microelectrode (e-NCNF) demonstrated high electrocatalytic capability for AA oxidation with a low working potential, 0 V, resulting in high selectivity for detection of AA level against other biological species in brain, as well as producing high sensitivity. Moreover, the e-NCNF was directly assembled by carbon nanotube bundles, free from the post-modification, thus showing high reproducibility, in which the deviation of anodic current intensity of six electrodes prepared with same method did not exceed 4% (RSD, n = 6). Based on the remarkable analytical performance, the e-NCNF with good biocompatibility was successfully applied to determine the AA level as 134 ± 7 mM, in rat brain microdialysates.
Co-reporter:Hong Huang, Fangyuan Dong, and Yang Tian
Analytical Chemistry 2016 Volume 88(Issue 24) pp:
Publication Date(Web):November 14, 2016
DOI:10.1021/acs.analchem.6b03470
Intracellular pH undertakes critical functions in the formation of a proton gradient and electrochemical potential that drives the adenosine triphosphate synthesis. It is also involved in various metabolic processes occurring in mitochondria, such as the generation of reactive oxygen species, calcium regulation, as well as the triggering of cell proliferation and apoptosis. Meanwhile, the aberrant accumulation of O2•– within mitochondria is frequently intertwined with mitochondrial dysfunction and disease development. To disentangle the complicated inter-relationship between pH and O2•– in the signal transduction and homeostasis in mitochondria, herein we developed a mitochondria-targeted single fluorescent probe for simultaneous sensing and imaging of pH and O2•– in mitochondria. CdSe/ZnS quantum dots encapsulated in silica shell was designed as an inner reference element for providing a built-in correction, as well as employed as a carrier to assemble the responsive elements for O2•– and pH, together with mitochondria-targeted molecule. The developed nanosensor demonstrated high accuracy and selectivity for pH and O2•– sensing, against other ROS, metal ions, and amino acids. The remarkable analytical performance of the present nanosensor, as well as good biocompatibility, established an accurate and selective approach for real-time imaging and biosensing of O2•– and pH in mitochondria of live cells.
Co-reporter:Yingying Han, Changqin Ding, Jie Zhou, and Yang Tian
Analytical Chemistry 2015 Volume 87(Issue 10) pp:5333
Publication Date(Web):April 21, 2015
DOI:10.1021/acs.analchem.5b00628
It is very essential to disentangle the complicated inter-relationship between pH and Cu in the signal transduction and homeostasis. To this end, reporters that can display distinct signals to pH and Cu are highly valuable. Unfortunately, there is still no report on the development of biosensors that can simultaneously respond to pH and Cu2+, to the best of our knowledge. In this work, we developed a single fluorescent probe, AuNC@FITC@DEAC (AuNC, gold cluster; FITC, fluorescein isothiocyanate; DEAC, 7-diethylaminocoumarin-3-carboxylic acid), for biosensing of pH, Cu2+, and pH/Cu2+ with different ratiometric fluorescent signals. First, 2,2′,2″-(2,2′,2″-nitrilotris(ethane-2,1-diyl)tris((pyridin-2-yl-methyl)azanediyl))triethanethiol (TPAASH) was designed for specific recognition of Cu2+, as well as for organic ligand to synthesize fluorescent AuNCs. Then, pH-sensitive molecule, FITC emitting at 518 nm, and inner reference molecule, DEAC with emission peak at 472 nm, were simultaneously conjugated on the surface of AuNCs emitting at 722 nm, thus, constructing a single fluorescent probe, AuNC@FITC@DEAC, to sensing pH, Cu2+, and pH/Cu2+ excited by 405 nm light. The developed probe exhibited high selectivity and accuracy for independent determination of pH and Cu2+ against reactive oxygen species (ROS), other metal ions, amino acids, and even copper-containing proteins. The AuNC-based inorganic–organic probe with good cell-permeability and high biocompatibility was eventually applied in monitoring both pH and Cu2+ and in understanding the interplaying roles of Cu2+ and pH in live cells by ratiometric multicolor fluorescent imaging.
Co-reporter:Limin Zhang, Yingying Han, Fan Zhao, Guoyue Shi, and Yang Tian
Analytical Chemistry 2015 Volume 87(Issue 5) pp:2931
Publication Date(Web):January 29, 2015
DOI:10.1021/ac504448m
Metals are essential components of all living cells, and in many cases cells trigger and utilize dynamic metal movements for signaling purposes. So, it is very critical to develop the biosensors for determination of metal ions in living systems with high selectivity and accuracy. In this work, taking Cu2+ as a model, an accurate and selective ratiometric electrochemical biosensor was developed. First, the specific molecule, 2,2′,2″-(2,2′,2″-nitrilotris(ethane-2,1-diyl)-tris((pyridin-2-ylmethyl)azanediyl)triethanethiol (TPAASH), was designed and synthesized for specific recognition of Cu2+. Meanwhile, electroactive molecule, 6-(ferrocenyl)hexanethiol (FcHT) was coimmobilized with TPAASH at one electrode as inner reference molecule to provide a built-in correction for avoiding the environmental effects. Thus, the developed biosensor demonstrated high accuracy and remarkable selectivity toward Cu2+ against other metal ions, amino acids, and so on. In addition, the biosensor also showed high sensitivity due to the electrocatalytic activity of the nanostructured gold flowers. As a result, the present ratiometric electrochemical biosensor was successfully applied in detection of Cu2+ in brain microdialysates of normal rat brain and that followed by global cerebral ischemia.
Co-reporter:Zhen Wang, Limin Zhang and Yang Tian
Analyst 2015 vol. 140(Issue 11) pp:3788-3793
Publication Date(Web):25 Nov 2014
DOI:10.1039/C4AN02003K
A non-enzymatic electrochemical H2O2 sensor was developed by in situ fabrication of biocompatible chitosan (CS) hydrogels, in which a specific recognition molecule for H2O2, thionine (TH), was stably immobilized via one-step electrodeposition. Electron transfer of TH was facilitated in the CS/GPTMS/TH (GPTMS: γ-glycidoxypropyltrimethoxysiloxane) hydrogels with an electron transfer rate constant (ks) of 3.5 ± 0.1 s−1. Meanwhile, TH in CS hydrogels maintained high electrocatalytic activity toward H2O2. The developed sensor exhibited a fast amperometric response toward H2O2 within 7 s and a linear response for H2O2 ranging from 5.0 × 10−6 to 6.9 × 10−4 M with a detection limit of 1.0 × 10−6 M. In addition, the non-enzymatic electrochemical sensor exhibited long-term stability with a current decrease less than 5.0% in 18 days and good reproducibility with a small deviation of 7.2%. The remarkable analytical performance of the present sensor provided a promising model for durable monitoring of H2O2 in rat brain microdialysates, which is very useful for understanding the biological effects of H2O2 on the pathological and physiological processes.
Co-reporter:Fang Liu, Changqin Ding, Ming Jin and Yang Tian
Analyst 2015 vol. 140(Issue 9) pp:3285-3289
Publication Date(Web):09 Mar 2015
DOI:10.1039/C5AN00277J
In this work, we developed a new two-photon fluorescent probe, ATD (ATD = amino triphenylamine dendron), by combining a two-photon fluorophore 4-(bis(4-(4-(diphenylamino)styryl)-phenyl)amino) benzaldehyde (TD) with a specific recognition molecule for Hg2+ – phenyl thiourea (PT) – for the determination of Hg2+. The designed fluorescent probe emitted at ∼455 nm upon one-photon and two-photon excitation at 400 nm and 800 nm, respectively. The blue fluorescence obviously dropped with the continuous addition of Hg2+, and demonstrated a good linearity with the concentration of Hg2+ in a wide dynamic range of 5 nM–1.0 μM. The detection limit achieved was 0.49 nM (∼0.2 ppb), which is much lower than the standard levels required by the U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO). Furthermore, this probe featured high selectivity for Hg2+ detection over other metal ions such as Cd2+, Ag+, Pd2+, and so on, due to the specific Hg2+ recognition by the PT molecule. Meanwhile, the probe demonstrated long-term stability with respect to pH and illumination. As a result, the developed two-photon fluorescent probe, with high sensitivity and selectivity, was successfully applied for the on-site determination of Hg2+ in environmental water samples.
Co-reporter:Yongping Luo, Chuan Dong, Xiaogang Li, Yang Tian
Journal of Electroanalytical Chemistry 2015 Volume 759(Part 1) pp:51-54
Publication Date(Web):15 December 2015
DOI:10.1016/j.jelechem.2015.05.021
•We develop a novel photoelectrochemical sensor for Pb2+ ion.•This method shows high selectivity, broad linear range, and low detection limit.•The approach has successfully applied for Pd2+ detection in tap water samples.A selective and sensitive photoelectrochemical sensor for lead ion (Pb2+), which is based on the generated photocurrents of lead sulfide (PbS) nanoparticles under visible light irradiation, has been developed with theoretical and technical simplicity. The PbS nanoparticles are in-situ electrodeposited onto TiO2 nanotube arrays with the gradual addition of Pb2+. The present sensor shows high selectivity against other metal ions, broad linear range from 10−8 M to 10−5 M, and low detection limit of 0.39 nM (∼0.08 ppb), which is much lower than the standard of Pb2+ in drinking water formulated by World Health Organization (WHO). Thus, the strategy has been applied to successful detection of Pb2+ in tap and lake water samples. The results for determination of Pb2+ in lake water samples obtained by the present method and atomic adsorption spectroscopy (AAS) are consistent. However, the detection of Pb2+ in tap water samples has just been realized by the present method, but AAS cannot, because of its low detection limit.
Co-reporter:Jun Ma, Changqin Ding, Jie Zhou, Yang Tian
Biosensors and Bioelectronics 2015 70() pp: 202-208
Publication Date(Web):
DOI:10.1016/j.bios.2015.03.033
Co-reporter:Changqin Ding, Yang Tian
Biosensors and Bioelectronics 2015 Volume 65() pp:183-190
Publication Date(Web):15 March 2015
DOI:10.1016/j.bios.2014.10.034
•A ratiometric fluorescence biosensor for pH determination, FA-FITC@AuNC, was developed for specific bioimaging and biosensing in cancer cells at the same time.•The developed biosensor can monitor pH gradients in a broad pH range of 6.0–7.8 with good sensitivity, high cyclic accuracy, and excellent selectivity over various metal ions and biological species.•The pH biosensor was also successfully used in targeted imaging for FR+ve Hela cells and FR−ve lung carcinoma cells A549.•This work can be extended to construct future ratiometric fluorescent biosensors for targeted imaging, drug deliver, or determination of other biomolecules, such as metal ions, proteins, and other biological relevant species in live cells, tissues, and animals.The dysregulated pH is working as a mark of cancer. It is a challenge for developing a biosensor for targeted imaging in cancer cells and monitoring of intracellular pH. Here, a ratiometric fluorescence biosensor for pH determination was developed with targeted imaging into folate acceptor (FR)-rich cancer cells at the same time. AuNCs protected by bovine serum albumin (BSA) worked as reference fluorophore and fluorescein-isothiocyanate (FITC) acted as the response signal for pH. For targeted imaging of cancer cells, the AuNCs were simultaneously conjugated with folic acid (FA). The developed ratiometric biosensor can monitor pH with a wide linear range from 6.0–7.8 with a pKa at 6.84. Under every different pH condition, the probe showed high selectivity over various metal ions and amino acids with its fluorescence ratio stayed almost constant (<5%). It also showed good cyclic accuracy when pH switched between 6.0 and 8.0, as well as low cytotoxicity. The AuNC-based inorganic–organic nanohybrid biosensor showed good cell-permeability, low cytotoxicity, and long-term photostability. Accordingly, the pH biosensor was employed to gain targeted imaging in FR+ve Hela cells with FR−ve lung carcinoma cells A549 as comparison, and achieved to monitor the pH changes in Hela cells.
Co-reporter:Dr. Yongping Luo;Dr. Limin Zhang;Dr. Wei Liu;Dr. Yanyan Yu; Yang Tian
Angewandte Chemie 2015 Volume 127( Issue 47) pp:
Publication Date(Web):
DOI:10.1002/ange.201508635
Abstract
Copper ion (Cu2+) and L-cysteine (CySH) are closely correlated with physiological and pathological events of Alzheimer’s Disease (AD), however the detailed mechanism is still unclear, mainly owing to a lack of accurate analytical methods in live brains. Herein, we report a single biosensor for electrochemical ratiometric detection of Cu2+ and CySH in live rat brains with AD. N,N-di-(2-picoly)ethylenediamine (DPEA) is first synthesized for specific recognition of Cu2+ to form a DPEA–Cu2+ complex. This complex shows high selectivity for CySH owing to the release of Cu2+ from the complex through CySH binding to Cu2+ center. In parallel, 5′-MB-GGCGCGATTTTTTTTTTTTT-SH-3′ (HS-DNA-MB, MB=Methylene Blue) is designed as an inner-reference for providing a built-in correction to improve the accuracy. As a result, combined with the amplified effect of Au nanoleaves, our single ratiometric biosensor can be successfully applied in real-time detection of Cu2+ and CySH in the live rat brains with AD. To our knowledge, this is the first report on the accurate concentrations of Cu2+ and CySH in live rat brains with AD.
Co-reporter:Dr. Yongping Luo;Dr. Limin Zhang;Dr. Wei Liu;Dr. Yanyan Yu; Yang Tian
Angewandte Chemie International Edition 2015 Volume 54( Issue 47) pp:
Publication Date(Web):
DOI:10.1002/anie.201508635
Abstract
Copper ion (Cu2+) and L-cysteine (CySH) are closely correlated with physiological and pathological events of Alzheimer’s Disease (AD), however the detailed mechanism is still unclear, mainly owing to a lack of accurate analytical methods in live brains. Herein, we report a single biosensor for electrochemical ratiometric detection of Cu2+ and CySH in live rat brains with AD. N,N-di-(2-picoly)ethylenediamine (DPEA) is first synthesized for specific recognition of Cu2+ to form a DPEA–Cu2+ complex. This complex shows high selectivity for CySH owing to the release of Cu2+ from the complex through CySH binding to Cu2+ center. In parallel, 5′-MB-GGCGCGATTTTTTTTTTTTT-SH-3′ (HS-DNA-MB, MB=Methylene Blue) is designed as an inner-reference for providing a built-in correction to improve the accuracy. As a result, combined with the amplified effect of Au nanoleaves, our single ratiometric biosensor can be successfully applied in real-time detection of Cu2+ and CySH in the live rat brains with AD. To our knowledge, this is the first report on the accurate concentrations of Cu2+ and CySH in live rat brains with AD.
Co-reporter:Xiaolan Chai, Limin Zhang, and Yang Tian
Analytical Chemistry 2014 Volume 86(Issue 21) pp:10668
Publication Date(Web):October 1, 2014
DOI:10.1021/ac502521f
A selective, accurate, and sensitive method for monitoring of cadmium ions (Cd2+) based on a ratiometric electrochemical sensor was developed, by simultaneously modifying with protoporphyrin IX and 6-(ferroceney) hexanethiol (FcHT) on Au particle-deposited glassy carbon electrode. On the basis of high affinity of biomolecular recognition between protoporphyrin IX and Cd2+, the functionalized electrode showed high selectivity toward Cd2+ over other metal ions such as Cu2+, Fe3+, Ca2+, and so on. Electroactive FcHT played the role as the inner reference element to provide a built-in correction, thus improving the accuracy for determination of Cd2+ in the complicated environments. The sensitivity of the electrochemical sensor for Cd2+ was enhanced by ∼3-fold through the signal amplification of electrodeposited gold nanoparticles. Accordingly, the present ratiometric method demonstrated high sensitivity, broad linear range from 100 nM to 10 μM, and low detection limit down to 10 nM (2.2 ppb), lower than EPA and WHO guidelines. Finally, the ratiometric electrochemical sensor was successfully applied in the determination of Cd2+ in water samples, and the obtained results agreed well with those obtained by the conventional ICP-MS method.
Co-reporter:Xiang Gao, Changqin Ding, Anwei Zhu, and Yang Tian
Analytical Chemistry 2014 Volume 86(Issue 14) pp:7071
Publication Date(Web):June 16, 2014
DOI:10.1021/ac501499y
In this article, a ratiometric fluorescent biosensor for O2•– was developed, by employing carbon dots (C-Dots) as the reference fluorophore and hydroethidine (HE), a specific organic molecule toward O2•–, playing the role as both specific recognition element and response signal. The hybrid fluorescent probe CD-HE only emitted at 525 nm is ascribed to C-Dots, while HE was almost nonfluorescent, upon excitation at 488 nm. However, after reaction with O2•–, a new emission peak ascribed to the reaction products of HE and O2•– was clearly observed at 610 nm. Meanwhile, this peak gradually increased with the increasing concentration of O2•– but the emission peak at 525 nm stayed constant, leading to a ratiometric detection of O2•–. The inorganic–organic fluorescent sensor exhibited high sensitivity, a broad dynamic linear range of ∼5 × 10–7–1.4 × 10–4 M, and low detection limit down to 100 nM. The present probe also showed high accuracy and excellent selectivity for O2•– over other reactive oxygen species (ROS), metal ions, and so on. Moreover, the C-Dot-based inorganic–organic probe demonstrated long-term stability against pH changes and continuous light illumination, good cell-permeability, and low cytotoxicity. Accordingly, the developed fluorescent biosensor was eventually applied for intracellular bioimaging and biosensing of O2•– changes upon oxidative stress.
Co-reporter:Qing Ye, Wei Li, Zhen Wang, Limin Zhang, Xiangshi Tan, Yang Tian
Journal of Electroanalytical Chemistry 2014 Volume 729() pp:21-26
Publication Date(Web):1 September 2014
DOI:10.1016/j.jelechem.2014.06.029
•Direct electron transfer of four new kinds of SODs is realized at MPA/AuF/GC electrode.•The electrochemical parameters depend on metal centers and microenviornments of the SODs.•Except Ni-SOD, the other three kinds of SODs show a bifunctional electrocatalytic activity to O2−.•Sensitive and selective biosensor for O2− was constructed.In this work, direct electrochemistry and electrocatalytic activity of four new kinds of artificially prepared superoxide dismutases (SODs) from human pathogen Clostridium difficile with different metal centers and microenvironments, that is, manganese superoxide dismutase (Mn-SOD), azide ion-coordinated manganese superoxide dismutase (Mn(N3−)-SOD), iron superoxide dismutase (Fe-SOD), and nickel superoxide dismutase (Ni-SOD), are systematically investigated. The direct electron transfer of the SODs is realized by 3-mercaptopropionic acid (MPA) confined on gold flowers electrodeposited onto glassy carbon electrode. The electrochemical parameters are dependent on the metal centers and microenvironments of the SODs with respect to the formal potential, reversibility of electrode reactions, and kinetic rate constant. Furthermore, except Ni-SOD, the other three kinds of SODs all exhibit a bifunctional electrocatalytic activity toward O2−. The combination of the enhanced electron transfer and the enzyme catalytic activities of SODs enables a sensitive and selective determination of O2−.Graphical abstract
Co-reporter:Qiao Xu, Wei Liu, Li Li, Feng Zhou, Jian Zhou and Yang Tian
Chemical Communications 2017 - vol. 53(Issue 11) pp:NaN1883-1883
Publication Date(Web):2017/01/12
DOI:10.1039/C6CC09563A
Herein, a ratiometric SERS probe was created for monitoring nitric oxide (NO) by designing a novel molecule, 3,4-diaminobenzene-thiol, and immobilizing this molecule onto trisoctahedral gold nanostructures with superior SERS capability. The established probe possessed good selectivity and biocompatibility, high sensitivity and accuracy, thus enabling imaging and biosensing of NO in live cells.
Co-reporter:Fan Zhao, Limin Zhang, Anwei Zhu, Guoyue Shi and Yang Tian
Chemical Communications 2016 - vol. 52(Issue 18) pp:NaN3720-3720
Publication Date(Web):2016/01/25
DOI:10.1039/C5CC09540A
pH plays an important role in the biochemical, ion-regulatory, or electrical machinery of nerve and glial cells, and is considered to be related to a number of degenerative diseases. Herein, we first develop a two-channel electrochemical ratiometric biosensor for local pH determination in a live rat brain, and report the accurate pH values in the different regions of live brains upon global cerebral ischemia.
Co-reporter:Fangyuan Dong, Tingting Zheng, Rongrong Zhu, Shilong Wang and Yang Tian
Journal of Materials Chemistry A 2016 - vol. 4(Issue 47) pp:NaN7688-7688
Publication Date(Web):2016/10/31
DOI:10.1039/C6TB02589G
Medical applications of nanotechnology typically focus on biosensors and drug delivery. Here, we combine nanotechnology and chemical synthesis to create a novel type of thermo-sensitive nanohybrid (CD-MSN@UP38) particle for intracellular temperature sensing and temperature-controlled drug release, which could lead to new cancer diagnosis techniques and therapies. The nanohybrid particles were first developed as a sensitive thermometer by loading them with a polarity-sensitive dye (BBD). The presented thermometer possessed high temporal resolution and temperature resolution down to 0.2 °C; combined with fluorescence lifetime imaging microscopy, the particles are well suited for mapping and sensing temperature distributions at the single-cell level. More interestingly, the nanohybrid particles can be further applied as a smart temperature-controlled drug delivery system for cancer therapy, through simply being triggered by the thermal effects of the cancer cells themselves. Our drug delivery and therapy system demonstrates highly efficient therapeutics with minimal side effects.
.jpg)
![Methyl (3s,4r)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate](http://img.cochemist.com/ccimg/100/50-36-2.png)
![Methyl (3s,4r)-3-benzoyloxy-8-methyl-8-azabicyclo[3.2.1]octane-4-carboxylate](http://img.cochemist.com/ccimg/100/50-36-2_b.png)
![Ethanol, 2-[2-(2-methoxyethoxy)ethoxy]-, 1-(4-methylbenzenesulfonate)](/data/chemimg/636900/62921-74-8.png)
![Ethanol, 2-[2-(2-methoxyethoxy)ethoxy]-, 1-(4-methylbenzenesulfonate)](/data/chemimg/636900/62921-74-8_b.png)
