Publications by authors named "Juqiang Lin"

34 Publications

Quantitative detection of crystal violet using a surface-enhanced Raman scattering based on a flower-like HAp/Ag nanocomposite.

Anal Methods 2021 Sep 23;13(36):4143-4149. Epub 2021 Sep 23.

MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China.

Herein, we proposed a simple one-pot sol-thermal strategy to prepare a highly sensitive and reproducible SERS substrate. The silver-doped hydroxyapatite nanocomposite (HAp/Ag) could suppress the oxidation of silver nanoparticles, which endow the SERS substrate with good stability and reproducibility. Due to the strong interaction between the HAp/Ag substrate and the analytes, a stronger Raman signal generated during the process of SERS detection. In particular, the HAp/Ag substrate enabled the determination of rhodamine 6G (R6G) and crystal violet (CV), and the limits of detection (LOD) were low at 10 M and 10 M, respectively. In addition, the HAp/Ag substrate could be used for the quantitative analysis of CV in wastewater with a good linear relationship between 10 and 10 M. In this context, the HAp/Ag substrate combines the superior properties of both Ag NPs and HAp particles, providing a potential method for monitoring the environment and building a convenient SERS platform to detect pollutants in wastewater.
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http://dx.doi.org/10.1039/d1ay01107cDOI Listing
September 2021

Study on degranulation of mast cells under C48/80 treatment by electroporation-assisted and ultrasound-assisted surface-enhanced Raman spectrascopy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Aug 27;265:120331. Epub 2021 Aug 27.

MOE Key Laboratory of Optoelectronic Science and Technology for Medicine and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China; School of opto-electronic and Communication Engineering, Xiamen University of Technology, Xiamen, Fujian, China. Electronic address:

Both electroporation-assisted and ultrasound-assisted delivery methods can rapidly deliver nanoparticles into living cells for surface-enhanced Raman scattering (SERS) detection, but these two methods have never been compared. In this study, electroporation-assisted SERS and ultrasound-assisted SERS were employed to detect the biochemical changes of degranulated mast cells induced by mast cell stimulator (C48/80). The results showed that the cell damage of electroporation based on controllable electric pulse was smaller than that of ultrasound based on cavitation. Transmission electron microscope images of cells indicated that the nanoparticles delivered by electroporation were mainly distributed in the cytoplasm, while ultrasound could transport nanoparticles to the cytoplasm and nucleus. Therefore, electroporation-assisted SERS mainly detects the biochemical information of cytoplasm, while ultrasound-assisted SERS gets more spectral signals of nucleic acid. Both methods can obtain high quality SERS signal of cells. With drug treatment, the SERS peak intensity of 733 cm attributed to phosphatidylserine decreased significantly, which may be due to the activation of mast cell degranulation pathway stimulated by C48/80 agonist, resulting in a large amount of intracellular serine being used to synthesize tryptase, while the production of phosphatidylserine decreased. Further, based on principal component analysis and linear discriminant analysis (PCA-LDA approach), ultrasound-assisted SERS could achieve better sensitivity, specificity and accuracy in the discrimination and identification of drug-treated degranulated mast cells than electroporation assisted SERS. This exploratory work is helpful to realize the real-time dynamic SERS detection of intracellular biochemical components, and it also has great potential in intracellular SERS analysis, such as the cytotoxicity assay of anti-tumor drugs or cancer cell screening.
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http://dx.doi.org/10.1016/j.saa.2021.120331DOI Listing
August 2021

Label-free determination of liver cancer stages using surface-enhanced Raman scattering coupled with preferential adsorption of hydroxyapatite microspheres.

Anal Methods 2021 Sep 16;13(35):3885-3893. Epub 2021 Sep 16.

MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China.

Here, we explored a label-free albumin targeted analysis method by utilizing hydroxyapatite (HAp) to adsorb-release serum albumin, in conjunction with surface-enhanced Raman scattering (SERS) for screening liver cancer (LC) at different tumor (T) stages. Excitingly, albumin can be preferentially adsorbed by HAp as compared with other serum proteins. Moreover, we developed a novel strategy using a high concentration of PO solution as the albumin-release agent. This method overcomes the shortcomings of the traditional purification technology of serum albumin, which requires acid to release protein, and ensures that the structure and properties of albumin are not damaged. The SERS spectra of serum albumin obtained from three sample groups were analyzed to verify the feasibility of this new method: healthy volunteers ( = 35), LC patients with T1 stage ( = 25) and LC patients with T2-T4 stage ( = 23). Furthermore, principal component analysis (PCA) combined with linear discriminant analysis (LDA) was employed to classify the early T (T1) stage LC normal group and advanced T (T2-T4) stage LC normal group, yielding high diagnostic accuracies of 90.00% and 96.55%, respectively, which showed a 10% improvement in diagnostic accuracy for the early stage detection of cancer as compared with previous studies. The results of this exploratory work demonstrated that HAp-adsorbed-released serum albumin combined with SERS analysis has great potential for label-free, noninvasive and sensitive detection of different T stages of liver cancer.
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http://dx.doi.org/10.1039/d1ay00946jDOI Listing
September 2021

Label-free diagnosis of breast cancer based on serum protein purification assisted surface-enhanced Raman spectroscopy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Dec 28;263:120234. Epub 2021 Jul 28.

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China; School of opto-electronic and Communication Engineering, Xiamen University of Technology, Xiamen, Fujian, China. Electronic address:

Serum protein is generally used to assess the severity of disease, as well as cancer progression and prognosis. Herein, a simple and rapid serum proteins analysis method combined with surface-enhanced Raman spectroscopy (SERS) technology was applied for breast cancer detection. The cellulose acetate membrane (CA) was employed to extract human serum proteins from 30 breast cancer patients and 45 healthy volunteers and then extracted proteins were mixed with silver nanoparticles for SERS measurement. Additionally, we also mainly assessed the use of different ratios of proteins-silver nanoparticles (Ag NPs) mixture to generate maximum SERS signal for clinical samples detection. Two multivariate statistical analyses, principal component analysis-linear discriminate analysis (PCA-LDA) and partial least square-support vector machines (PLS-SVM) were used to analyze the obtained serum protein SERS spectra and establish the diagnostic model. The results demonstrate that the PLS-SVM model provides superior performance in the classification of breast cancer diagnosis compared with PCA-LDA. This exploratory work demonstrates that the label-free SERS analysis technique combined with CA membrane purified serum proteins has great potential for breast cancer diagnosis.
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http://dx.doi.org/10.1016/j.saa.2021.120234DOI Listing
December 2021

High spatio-temporal resolution measurement of A R and A R interactions combined with Iem-spFRET and E-FRET methods.

J Biophotonics 2021 Jul 30:e202100172. Epub 2021 Jul 30.

MOE Key Laboratory of OptoElectronic Science and Technology for Medicine and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China.

A R-A R heterodimers regulate striatal glutamatergic neurotransmission. However, few researches about kinetics have been reported. Here, we combined Iem-spFRET and E-FRET to investigate the kinetics of A R and A R interaction. Iem-spFRET obtains the energy transfer efficiency of the whole cell. E-FRET gets energy transfer efficiency with high spatial resolution, whereas, it was prone to biases because background was easily selected due to manual operation. To study the interaction with high spatio-temporal resolution, Iem-spFRET was used to correct the deviation of E-FRET. In this paper, A R and A R interaction was monitored, and the changes of FRET efficiency of the whole or/and partial cell membrane were described. The results showed that activation of A R or A R leads to rapid aggregation, inhibition of A R or A R leads to slow segregation, and the interaction is reversible. These results demonstrated that combination of Iem-spFRET and E-FRET could measure A R and A R interaction with high spatio-temporal resolution.
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http://dx.doi.org/10.1002/jbio.202100172DOI Listing
July 2021

A microsphere nanoparticle based-serum albumin targeted adsorption coupled with surface-enhanced Raman scattering for breast cancer detection.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 1;261:120039. Epub 2021 Jun 1.

MOE Key Laboratory of OptoElectronic Science and Technology for Medicine and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China. Electronic address:

The serum albumin level is inseparable associated with survival in patients with breast cancer, and simultaneously serve as a good indicator of prognosis of cancer. Here, we proposed a novel extraction-isolation analysis method of albumin for breast cancer detection utilizing hydroxyapatite particles (HAp) to targeted adsorb albumin from serum relying on its specific adsorption capacity. An ideal protein-release reagent was used for isolating albumin from the surface of HAp, and meanwhile ensuring that the structure and property of albumin was not suffered damage. The surface-enhanced Raman scattering (SERS) signal of extracted albumin was obtained, and partial least squares (PLS) and linear discriminant analysis (LDA) analysis approach were employed to analyze SERS spectra data, with the aim to assess the capability of HAp method for identifying breast cancer, yielding an ideal diagnostic accuracy of 98.6%, demonstrating promising potential as a non-invasive and sensitive nanotechnology for breast cancer screening.
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http://dx.doi.org/10.1016/j.saa.2021.120039DOI Listing
November 2021

Label-free Raman spectroscopy: A potential tool for early diagnosis of diabetic keratopathy.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 22;256:119731. Epub 2021 Mar 22.

Key Laboratory of Opto-Electronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, China. Electronic address:

Diabetes has become a major public health problem worldwide, and the incidence of diabetes has been increasing progressively. Diabetes is prone to cause various complications, among which diabetic keratopathy (DK) emphasizes the significant impact on the cornea. The current diagnosis of DK lacks biochemical markers that can be used for early and non-invasive screening and detection. In contrast, in this study, Raman spectroscopy, which demonstrates non-destructive, label-free features, especially the unique advantage of providing molecular fingerprint information for target substances, were utilized to interrogate the intrinsic information of the corneal tissues from normal and diabetic mouse models, respectively. Visually, the Raman spectral response derived from the biochemical components and biochemical differences between the two groups were compared. Moreover, multivariate analysis methods such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were carried out for advanced statistical analysis. PCA yields a diagnostic results of 57.4% sensitivity, 89.2% specificity, 74.8% accuracy between the diabetic group and control group; Moreover, PLS-DA was employed to enhance the diagnostic ability, showing 76.1% sensitivity, 86.1% specificity, and 87.6% accuracy between the diabetic group and control group. Our proof-of-concept results show the potential of Raman spectroscopy-based techniques to help explore the underlying pathogenesis of DK disease and thus be further expanded for potential applications in the early screening of diabetic diseases.
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http://dx.doi.org/10.1016/j.saa.2021.119731DOI Listing
July 2021

Surface-enhanced Raman scattering analysis of serum albumin via adsorption-exfoliation on hydroxyapatite nanoparticles for noninvasive cancers screening.

J Biophotonics 2020 08 2;13(8):e202000087. Epub 2020 Jun 2.

MOE Key Laboratory of OptoElectronic Science and Technology for Medicine and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, China.

Combining serum albumin via adsorption-exfoliation on hydroxyapatite particles (HAp) with surface-enhanced Raman scattering (SERS), we developed a novel quantitative analysis of albumin method from blood serum for cancers screening applications. The quantitatively analysis obtained by our HAp method had a good linear relationship from 1 to 10 g/dL, and the lower limit of detection was less than the albumin prognostic factor for disease (3.5 g/dL). Serum albumin was adsorbed and exfoliated by HAp from serum samples of liver cancer patients, breast cancer patients and healthy volunteers and mixed with silver colloids to perform SERS spectral analysis. Based on the PLS-SVM algorithm, the diagnostic accuracies of liver cancer patients and breast cancer patients were 100% and 96.68%, respectively. Moreover, this algorithm successfully predicted the unidentified subjects with a diagnostic accuracy of 93.75%. This exploratory work demonstrated that HAp-adsorbed-exfoliated serum proteins combined with SERS spectroscopy has great potential for cancer screening.
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http://dx.doi.org/10.1002/jbio.202000087DOI Listing
August 2020

Filter-Membrane-Based Ultrafiltration Coupled with Surface-Enhanced Raman Spectroscopy for Potential Differentiation of Benign and Malignant Thyroid Tumors from Blood Plasma.

Int J Nanomedicine 2020 1;15:2303-2314. Epub 2020 Apr 1.

Fujian Normal University, Ministry of Education, Key Laboratory of Optoelectronic Science and Technology for Medicine, Fujian Provincial Key Laboratory for Photonics Technology, Fuzhou, People's Republic of China.

Objective: The objective of this study is to evaluate the performance and feasibility of surface-enhanced Raman spectroscopy coupled with a filter membrane and advanced multivariate data analysis on identifying and differentiating benign and malignant thyroid tumors from blood plasma.

Patients And Methods: We proposed a membrane filter SERS technology for the differentiation between benign thyroid tumor and thyroid cancer. That is to say, by using filter membranes with optimal pore size, the blood plasma samples from thyroid tumor patients were pretreated with the macromolecular proteins being filtered out prior to SERS measurement. The SERS spectra of blood plasma ultrafiltrate obtained using filter membranes from 102 patients with thyroid tumors (70 thyroid cancers and 32 benign thyroid tumors) were then analyzed and compared. Two multivariate statistical analyses, principal component analysis-linear discriminate analysis (PCA-LDA) and Lasso-partial least squares-discriminant analysis (Lasso-PLS-DA), were performed on the SERS spectral data after background subtraction and normalization, as well as the first derivative processing, to analyze and compare the differential diagnosis of benign thyroid tumors and thyroid cancer.

Results: SERS measurements were performed in blood plasma acquired from a total of 102 thyroid tumor patients (benign thyroid tumor N=32; thyroid cancer N=70). By using filter membranes, the macromolecular proteins in blood plasma were effectively filtered out to yield high-quality SERS spectra. 84.3% discrimination accuracy between benign and malignant thyroid tumor was achieved using PCA-LDA method, while Lasso-PLS-DA yields a discrimination accuracy of 90.2%.

Conclusion: Our results demonstrate that SERS spectroscopy, coupled with ultrafiltration and multivariate analysis has the potential of providing a non-invasive, rapid, and objective detection and differentiation of benign and malignant thyroid tumors.
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http://dx.doi.org/10.2147/IJN.S233663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132009PMC
August 2020

Surface-enhanced Raman spectroscopy analysis of mast cell degranulation induced by low-intensity laser.

IET Nanobiotechnol 2019 Dec;13(9):983-988

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, People's Republic of China.

Mast cell (MC) degranulation is an important step in the healing process. In this study, silver-nanoparticles-based surface-enhanced Raman spectroscopy (SERS) was used to investigate the spectral characteristics of degranulation of MCs activated by low-intensity laser. The significant spectral changes, such as Raman peak intensities, suggested the concentration variation of some degranulated substances. The Raman intensity ratio of 799-554 cm could be used as a potential internal indicator for the degranulation degree of MCs. Principal component analysis (PCA) was employed to reduce the high dimension of spectra into a few principal components (PCs) while retaining the most diagnostically significant information for sample differentiation. Using the diagnostically significant PC scores ( < 0.05), linear discriminate analysis (LDA) was applied to identify different cell degranulation groups with high sensitivity, specificity and accuracy. This exploratory work demonstrates that SERS technique combined with a PCA-LDA algorithm possesses great potential for developing a label-free, comprehensive, non-invasive and accurate method for measuring MC degranulation.
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http://dx.doi.org/10.1049/iet-nbt.2019.0145DOI Listing
December 2019

Label-free detection of nasopharyngeal and liver cancer using surface-enhanced Raman spectroscopy and partial lease squares combined with support vector machine.

Biomed Opt Express 2018 Dec 7;9(12):6053-6066. Epub 2018 Nov 7.

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou, Fujian, China.

In this paper, we investigated the feasibility of using surface enhanced Raman spectroscopy (SERS) and multivariate analysis method to discriminate liver cancer and nasopharyngeal cancer from healthy volunteers. SERS measurements were performed on serum protein samples from 104 liver cancer patients, 100 nasopharyngeal cancer patients, and 95 healthy volunteers. Two dimensionality reduction methods, principal component analysis (PCA) and partial least square (PLS) were compared, and the results indicated that the performance of PLS is superior to that of PCA. When the number of components was compressed to 3 by PLS, support vector machine (SVM) with a Gaussian radial basis function (RBF) was employed to classify various cancers simultaneously. Based on the PLS-SVM algorithm, high diagnostic accuracies of 95.09% and 90.67% were achieved from the training set and the unknown testing set, respectively. The results of this exploratory work demonstrate that serum protein SERS technology combined with PLS-SVM diagnostic algorithm has great potential for the noninvasive screening of cancer.
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http://dx.doi.org/10.1364/BOE.9.006053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490983PMC
December 2018

Leukemia cells detection based on electroporation assisted surface-enhanced Raman scattering.

Biomed Opt Express 2017 Sep 15;8(9):4108-4121. Epub 2017 Aug 15.

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou, Fujian, China.

In this study, an electroporation-based surface-enhanced Raman scattering (SERS) technique was employed to differentiate the human myeloid leukemia cells from the normal human bone marrow mononuclear cells with the aim to develop a fast and label-free method for leukemia cell screening. The Ag nanoparticles were delivered into living cells by electroporation, and then high quality SERS spectra were successfully obtained from 60 acute promyelocytic leukemia cells (HL60 cell line), 60 chronic myelogenous leukemia cells (K562 cell line) and 60 normal human bone marrow mononuclear cells (BMC). Principal component analysis (PCA) combined with linear discriminant analysis (LDA) differentiated the leukemia cell SERS spectra (HL60 plus K562) from normal cell SERS spectra (BMC) with high sensitivity (98.3%) and specificity (98.3%). Furthermore, partial least squares (PLS) approach was employed to develop a diagnostic model. The model successfully predicted the unidentified subjects with a diagnostic accuracy of 96.7%. This exploratory work demonstrates that the electroporation-based SERS technique combined with PCA-LDA and PLS diagnostic algorithms possesses great promise for cancer cell screening.
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http://dx.doi.org/10.1364/BOE.8.004108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611926PMC
September 2017

Ultrasound-mediated method for rapid delivery of nano-particles into cells for intracellular surface-enhanced Raman spectroscopy and cancer cell screening.

Nanotechnology 2015 Feb 19;26(6):065101. Epub 2015 Jan 19.

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, People's Republic of China.

Surface-enhanced Raman spectroscopy (SERS) is a powerful technology for providing finger-printing information of cells. A big challenge has been the long time duration and inefficient uptake of metal nano-particles into living cells as substrate for SERS analysis. Herein, a simple method (based on ultrasound) for the rapid transfer of silver nanoparticles (NPs) into living cells for intracellular SERS spectroscopy was presented. In this study, the ultrasound-mediated method for NP delivery overcame the shortcoming of 'passive uptake', and achieved quick acquisition of reproducible SERS spectra from living human nasopharyngeal carcinoma cell lines (C666 and CNE1) and normal nasopharyngeal cell line (NP69). Tentative assignment of the Raman bands in the measured SERS spectra showed cancer cell specific biomolecular differences, including significantly lower DNA concentrations and higher protein concentrations in cancerous nasopharyngeal cells as compared to those of normal cells. Combined with PCA-LDA multivariate analysis, ultrasound-mediated cell SERS spectroscopy differentiated the cancerous cells from the normal nasopharyngeal cells with high diagnostic accuracy (98.7%), demonstrating great potential for high-throughput cancer cell screening applications.
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http://dx.doi.org/10.1088/0957-4484/26/6/065101DOI Listing
February 2015

Gold nanoaggregates for probing single-living cell based on surface-enhanced Raman spectroscopy.

J Biomed Opt 2015 May;20(5):051005

Fujian Normal University, Ministry of Education and Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of Optoelectronic Science and Technology for Medicine, Fuzhou 350007, China.

Gold nanoparticles are delivered into living cells by transient electroporation method to obtain intracellular surface-enhanced Raman spectroscopy (SERS). The subcellular localization of gold nanoparticles is characterized by transmission electron microscopy, and the forming large gold nanoaggregates are mostly found in the cytoplasm. The SERS detection of cells indicates that this kind of gold nanostructures induces a high signal enhancement of cellular chemical compositions, in addition to less cellular toxicity than that of silver nanoparticles. These results demonstrate that rapid incorporation of gold nanoparticles by electroporation into cells has great potential applications in the studies of cell biology and biomedicine.
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http://dx.doi.org/10.1117/1.JBO.20.5.051005DOI Listing
May 2015

Label-free detection of serum proteins using surface-enhanced Raman spectroscopy for colorectal cancer screening.

J Biomed Opt 2014 Aug;19(8):087003

Fujian Normal University, Ministry of Education and Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of Optoelectronic Science and Technology for Medicine, Fuzhou 350007, China.

Surface-enhanced Raman scattering (SERS) spectra of serum proteins purified from human serum samples were employed to detect colorectal cancer. Acetic acid as a new aggregating agent was introduced to increase the magnitude of the SERS enhancement. High-quality SERS spectra of serum proteins were acquired from 103 cancer patients and 103 healthy volunteers. Tentative assignments of SERS bands reflect that some specific biomolecular contents and protein secondary structures change with colorectal cancer progression. Principal component analysis combined with linear discriminant analysis was used to assess the capability of this approach for identifying colorectal cancer, yielding diagnostic accuracies of 100% (sensitivity: 100%; specificity: 100%) based on albumin SERS spectroscopy and 99.5% (sensitivity: 100%; specificity: 99%) based on globulin SERS spectroscopy, respectively. A partial least squares (PLS) approach was introduced to develop diagnostic models. An albumin PLS model successfully predicted the unidentified subjects with a diagnostic accuracy of 93.5% (sensitivity: 95.6%; specificity: 91.3%) and the globulin PLS model gave a diagnostic accuracy of 93.5% (sensitivity: 91.3%; specificity: 95.6%). These results suggest that serum protein SERS spectroscopy can be a sensitive and clinically powerful means for colorectal cancer detection.
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http://dx.doi.org/10.1117/1.JBO.19.8.087003DOI Listing
August 2014

Rapid and nondestructive method for evaluation of embryo culture media using drop coating deposition Raman spectroscopy.

J Biomed Opt 2013 Dec;18(12):127003

Fujian Normal University, Key Laboratory of Opto-Electronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fuzhou 350007, ChinacImaging Unit-Integrative Oncology Department, British Columbia Cancer Agency Research Centre, Vancouver, British Columbia V5Z 1L3, Canada.

In this study, a rapid and simple method which combines drop coating deposition and Raman spectroscopy (DCDR) was developed to characterize the dry embryo culture media (ECM) droplet. We demonstrated that Raman spectra obtained from the droplet edge presented useful and characteristic signatures for protein and amino acids assessment. Using a different analytical method, scanning electron microscopy coupled with energy dispersive X-ray analysis, we further confirmed that Na, K, and Cl were mainly detected in the central area of the dry ECM droplet while sulphur, an indicative of the presence of macromolecules such as proteins, was mainly found at the periphery of the droplet. In addition, to reduce sample preparation time, different temperatures for drying the droplets were tested. The results showed that drying temperature at 50°C can effectively reduce the sample preparation time to 6 min (as compared to 50 min for drying at room temperature, ∼25°C) without inducing thermal damage to the proteins. This work demonstrated that DCDR has potential for rapid and reliable metabolomic profiling of ECM in clinical applications.
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http://dx.doi.org/10.1117/1.JBO.18.12.127003DOI Listing
December 2013

Quantitative determination of citric acid in seminal plasma by using Raman spectroscopy.

Appl Spectrosc 2013 Jul;67(7):757-60

Key Laboratory of Opto-Electronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou 350007, People's Republic of China.

In this study, Raman spectroscopy was first used to study the linear relationship between Raman spectral intensities and citric acid concentrations in aqueous solution. By using the specific Raman band of 942 cm(-1), concentrations of citric acid ranging from 2 to 20 mg/mL were observed linearly (R(2) = 0.993), and the limit of detection was 1.0 mg/mL. Then, citric acid detection in clinical seminal plasma ultrafiltrate samples was performed, and the intensity of the Raman-specific peak demonstrates a good linear correlation (R(2) = 0.946) with citric acid concentrations determined by the enzymatic method. Our results showed that Raman spectroscopy has the potential of being applied to detect concentrations of citric acid in seminal plasma in clinic.
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http://dx.doi.org/10.1366/12-06902DOI Listing
July 2013

Blood plasma surface-enhanced Raman spectroscopy for non-invasive optical detection of cervical cancer.

Analyst 2013 Jul 25;138(14):3967-74. Epub 2013 Mar 25.

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, China.

Based on blood plasma surface-enhanced Raman spectroscopy (SERS) analysis, a simple and label-free blood test for non-invasive cervical cancer detection is presented in this paper. SERS measurements were performed on blood plasma samples from 60 cervical cancer patients and 50 healthy volunteers. Both the empirical approach and multivariate statistical techniques, including principal component analysis (PCA) and linear discriminant analysis (LDA), were employed to analyze and differentiate the obtained blood plasma SERS spectra. The empirical diagnostic algorithm based on the integration area of the SERS spectral bands (1310-1430 and 1560-1700 cm(-1)) achieved a diagnostic sensitivity of 70% and 83.3%, and a specificity of 76% and 78%, respectively, whereas the diagnostic algorithms based on PCA-LDA yielded a better diagnostic sensitivity of 96.7% and a specificity of 92% for separating cancerous samples from normal samples. This exploratory work demonstrates that a silver nanoparticle based SERS plasma analysis technique in conjunction with PCA-LDA has potential for improving cervical cancer detection and screening.
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http://dx.doi.org/10.1039/c3an36890dDOI Listing
July 2013

Investigation of free fatty acid associated recombinant membrane receptor protein expression in HEK293 cells using Raman spectroscopy, calcium imaging, and atomic force microscopy.

Anal Chem 2013 Feb 23;85(3):1374-81. Epub 2013 Jan 23.

Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, China.

G-protein-coupled receptor 120 (GPR120) is a previously orphaned G-protein-coupled receptor that apparently functions as a sensor for dietary fat in the gustatory and digestive systems. In this study, a cDNA sequence encoding a doxycycline (Dox)-inducible mature peptide of GPR120 was inserted into an expression vector and transfected in HEK293 cells. We measured Raman spectra of single HEK293 cells as well as GPR120-expressing HEK293-GPR120 cells at a 48 h period following the additions of Dox at several concentrations. We found that the spectral intensity of HEK293-GPR120 cells is dependent upon the dose of Dox, which correlates with the accumulation of GPR120 protein in the cells. However, the amount of the fatty acid activated changes in intracellular calcium (Ca(2+)) as measured by ratiometric calcium imaging was not correlated with Dox concentration. Principal components analysis (PCA) of Raman spectra reveals that the spectra from different treatments of HEK293-GPR120 cells form distinct, completely separated clusters with the receiver operating characteristic (ROC) area of 1, while those spectra for the HEK293 cells form small overlap clusters with the ROC area of 0.836. It was also found that expression of GPR120 altered the physiochemical and biomechanical properties of the parental cell membrane surface, which was quantitated by atomic force microscopy (AFM). These findings demonstrate that the combination of Raman spectroscopy, calcium imaging, and AFM may provide new tools in noninvasive and quantitative monitoring of membrane receptor expression induced alterations in the biophysical and signaling properties of single living cells.
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http://dx.doi.org/10.1021/ac3020577DOI Listing
February 2013

[Surface-enhanced Raman spectroscopic analysis of uric acid].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2012 Jun;29(3):541-5

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, China.

Based on Ag nanoparticles as the surface-enhanced Raman spectroscopy (SERS)-active nanostructure, the SERS of uric acid was presented in the paper. The absorption spectroscopies of uric acid and the mixture of silver colloids and uric acid were measured. The possible enhancing mechanism of the uric acid on silver colloid was speculated. The characteristic SERS bands of uric acid were tentatively assigned. The influence of absorption time and different ion on the SERS of uric acid were also discussed. The SERS spectral intensity changes linearly with the uric acid concentration, which indicated that the SERS might provide a new kind of direct and fast detecting method for the detection of uric acid. The detection limit of uric acid in silver sol is found to be 1 mg/L.
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June 2012

Study on gastric cancer blood plasma based on surface-enhanced Raman spectroscopy combined with multivariate analysis.

Sci China Life Sci 2011 Sep 1;54(9):828-34. Epub 2011 Aug 1.

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education of China, Fujian Normal University, Fuzhou 350007, China.

A surface-enhanced Raman spectroscopy (SERS) method combined with multivariate analysis was developed for non-invasive gastric cancer detection. SERS measurements were performed on two groups of blood plasma samples: one group from 32 gastric patients and the other group from 33 healthy volunteers. Tentative assignments of the Raman bands in the measured SERS spectra suggest interesting cancer-specific biomolecular changes, including an increase in the relative amounts of nucleic acid, collagen, phospholipids and phenylalanine and a decrease in the percentage of amino acids and saccharide in the blood plasma of gastric cancer patients as compared with those of healthy subjects. Principal components analysis (PCA) and linear discriminant analysis (LDA) were employed to develop effective diagnostic algorithms for classification of SERS spectra between normal and cancer plasma with high sensitivity (79.5%) and specificity (91%). A receiver operating characteristic (ROC) curve was employed to assess the accuracy of diagnostic algorithms based on PCA-LDA. The results from this exploratory study demonstrate that SERS plasma analysis combined with PCA-LDA has tremendous potential for the non-invasive detection of gastric cancers.
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http://dx.doi.org/10.1007/s11427-011-4212-8DOI Listing
September 2011

Colorectal cancer detection by gold nanoparticle based surface-enhanced Raman spectroscopy of blood serum and statistical analysis.

Opt Express 2011 Jul;19(14):13565-77

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou, China.

The capabilities of using gold nanoparticle based surface-enhanced Raman spectroscopy (SERS) to obtain blood serum biochemical information for non-invasive colorectal cancer detection were presented in this paper. SERS measurements were performed on two groups of blood serum samples: one group from patients (n = 38) with pathologically confirmed colorectal cancer and the other group from healthy volunteers (control subjects, n = 45). Tentative assignments of the Raman bands in the measured SERS spectra suggested interesting cancer specific biomolecular changes, including an increase in the relative amounts of nucleic acid, a decrease in the percentage of saccharide and proteins contents in the blood serum of colorectal cancer patients as compared to that of healthy subjects. Both empirical approach and multivariate statistical techniques, including principal components analysis (PCA) and linear discriminant analysis (LDA) were employed to develop effective diagnostic algorithms for classification of SERS spectra between normal and colorectal cancer serum. The empirical diagnostic algorithm based on the ratio of the SERS peak intensity at 725 cm(-1) for adenine to the peak intensity at 638 cm(-1) for tyrosine achieved a diagnostic sensitivity of 68.4% and specificity of 95.6%, whereas the diagnostic algorithms based on PCA-LDA yielded a diagnostic sensitivity of 97.4% and specificity of 100% for separating cancerous samples from normal samples. Receiver operating characteristic (ROC) curves further confirmed the effectiveness of the diagnostic algorithm based on PCA-LDA technique. The results from this exploratory study demonstrated that gold nanoparticle based SERS serum analysis combined with PCA-LDA has tremendous potential for the non-invasive detection of colorectal cancers.
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http://dx.doi.org/10.1364/OE.19.013565DOI Listing
July 2011

A novel blood plasma analysis technique combining membrane electrophoresis with silver nanoparticle-based SERS spectroscopy for potential applications in noninvasive cancer detection.

Nanomedicine 2011 Oct 17;7(5):655-63. Epub 2011 Feb 17.

Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou, China.

Combining membrane electrophoresis with silver nanoparticle-based surface-enhanced Raman spectroscopy (SERS), we have developed a novel method for blood plasma analysis for cancer detection applications. In this method, total serum proteins are isolated from blood plasma by membrane electrophoresis and mixed with silver nanoparticles to perform SERS spectral analysis. The obtained SERS spectra present information-rich, fingerprint-type signatures of the biochemical constituents of whole proteins. We evaluated the utility of this method by analyzing blood plasma samples from patients with gastric cancer (n=31) and healthy volunteers (n=33). Principal components analysis of the spectra revealed that the data points for the two groups form distinct, completely separated clusters with no overlap. The gastric cancer group can be unambiguously distinguished from the normal group in this initial test-that is, with both diagnostic sensitivity and specificity of 100%. These results are very promising for developing a label-free, noninvasive clinical tool for cancer detection and screening.
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http://dx.doi.org/10.1016/j.nano.2011.01.012DOI Listing
October 2011

Gastric cancer detection based on blood plasma surface-enhanced Raman spectroscopy excited by polarized laser light.

Biosens Bioelectron 2011 Mar 17;26(7):3167-74. Epub 2010 Dec 17.

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou, China.

We have recently applied surface-enhanced Raman spectroscopy (SERS) for blood plasma analysis for non-invasive nasopharyngeal cancer detection and obtained good preliminary results. The aim of this study was to develop a more robust SERS spectroscopy based blood plasma analysis method for non-invasive gastric cancer detection. The effect of different laser polarizations (non-polarized, linear-polarized, right-handed circularly polarized, and left-handed circularly polarized) on blood plasma SERS spectroscopy was explored for the first time. Silver nanoparticles as the SERS-substrate were directly mixed with blood plasma to enhance the Raman scattering of various biomolecular constituents. High quality SERS spectra were obtained using a fiber optic probe and a dispersive type near infrared Raman system. Blood plasma samples from gastric cancer patients (n=32) and healthy subjects (n=33) were analyzed. The diagnostic performance for differentiating gastric cancer plasma from normal plasma was evaluated. Principal component analysis combined with linear discriminant analysis (LDA) of the obtained spectral data was used to develop diagnostic algorithms. Classification results obtained from cross-validation of the LDA model based on the four spectral data sets of different laser polarizations demonstrated different diagnostic sensitivities and specificities: 71.9% and 72.7% for non-polarized laser excitation, 75% and 87.9% for linear-polarized laser excitation, 81.3% and 78.8% for right-handed circularly polarized laser excitation, 100% and 97% for left-handed circularly polarized laser excitation. The results from this exploratory study demonstrated that plasma SERS spectroscopy with left-handed circularly polarized laser excitation has great promise of becoming a clinically useful diagnostic tool for non-invasive gastric cancer detection.
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http://dx.doi.org/10.1016/j.bios.2010.12.020DOI Listing
March 2011

In vitro imaging of thyroid tissues using two-photon excited fluorescence and second harmonic generation.

Photomed Laser Surg 2010 Aug;28 Suppl 1:S129-33

Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou, P. R. China.

Objective: To evaluate the feasibility of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) imaging to discriminate the normal, nodular goiter and papillary cancerous thyroid tissue.

Materials And Methods: In total, 45 fresh thyroid specimens (normal, 15; nodular goiter, 12; and papillary cancerous, 18) from 31 subjects were directly imaged by the TPEF and SHG combination method.

Results: The microstructure of follicle and collagen structure in thyroid tissue were clearly identified, morphologic changes between normal, nodular goiter, and papillary cancerous thyroid tissue were well characterized by using two-photon excitation fluorescence. SHG imaging of the collagen matrix also revealed the differences between normal and abnormal.

Conclusions: Our preliminary study suggests that the TPEF and SHG combination method might be a useful tool in revealing pathologic changes in thyroid tissue.
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http://dx.doi.org/10.1089/pho.2009.2563DOI Listing
August 2010

Nasopharyngeal cancer detection based on blood plasma surface-enhanced Raman spectroscopy and multivariate analysis.

Biosens Bioelectron 2010 Jul 1;25(11):2414-9. Epub 2010 Apr 1.

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, China.

A surface-enhanced Raman spectroscopy (SERS) method was developed for blood plasma biochemical analysis for the first time with the aim to develop a simple blood test for non-invasive nasopharyngeal cancer detection. Silver nanoparticles (Ag NP) as the SERS-active nanostructures were directly mixed with blood plasma to enhance the Raman scattering signals of various biomolecular constituents such as proteins, lipids, and nucleic acids. High quality SERS spectrum from blood plasma-Ag NP mixture can be obtained within 10s using a Renishaw micro-Raman system. SERS measurements were performed on two groups of blood plasma samples: one group from patients (n=43) with pathologically confirmed nasopharyngeal carcinomas (WHO type I, II, and III) and the other group from healthy volunteers (control subjects, n=33). Tentative assignments of the Raman bands in the measured SERS spectra suggest interesting cancer specific biomolecular differences, including an increase in the relative amounts of nucleic acid, collagen, phospholipids and phenylalanine and a decrease in the percentage of amino acids and saccharide contents in the blood plasma of nasopharyngeal cancer patients as compared to that of healthy subjects. Principal component analysis (PCA) of the measured SERS spectra separated the spectral features of the two groups into two distinct clusters with little overlaps. Linear discriminate analysis (LDA) based on the PCA generated features differentiated the nasopharyngeal cancer SERS spectra from normal SERS spectra with high sensitivity (90.7%) and specificity (100%). The results from this exploratory study demonstrated great potentials for developing SERS blood plasma analysis into a novel clinical tool for non-invasive detection of nasopharyngeal cancers.
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http://dx.doi.org/10.1016/j.bios.2010.03.033DOI Listing
July 2010

Gold nanoparticle based surface-enhanced Raman scattering spectroscopy of cancerous and normal nasopharyngeal tissues under near-infrared laser excitation.

Appl Spectrosc 2009 Oct;63(10):1089-94

Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007, China.

The capabilities of using gold nanoparticle based near-infrared surface-enhanced Raman scattering (SERS) to obtain biochemical information with high spatial resolution from human nasopharyngeal tissue were presented in this paper. The gold nanoparticles used have a mean diameter of 43 nm with a standard deviation of 6 nm. The SERS bands of nasopharyngeal tissue were assigned to known molecular vibrations of nucleic acids, amino acids, proteins, and metabolites. We also observed the blinking phenomenon at the tissue level when measuring the nasopharyngeal tissue SERS spectra, most frequently in signal intensity but also occasionally in peak positions. This phenomenon is excitation light intensity dependent. This work demonstrated great potential for using SERS imaging for distinguishing cancerous and normal nasopharyngeal tissues on frozen sections without using any dye labeling or other chemical species as functionalized binding sites.
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http://dx.doi.org/10.1366/000370209789553291DOI Listing
October 2009

Rapid delivery of silver nanoparticles into living cells by electroporation for surface-enhanced Raman spectroscopy.

Biosens Bioelectron 2009 Oct 3;25(2):388-94. Epub 2009 Aug 3.

Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou 350007, China.

In current intracellular surface-enhanced Raman spectroscopy (SERS) measurements, gold or silver nanoparticles are delivered into living cells by "passive uptake". This procedure is time-consuming, could take up to several to twenties hours of incubation with nanoparticles in the culture medium. It is a less optimal method for certain applications such as high-throughput disease screening. Here, we present a method based on electroporation for fast delivery of silver nanoparticles into living cells for intracellular SERS spectroscopy. This new method for nanoparticle delivery averts the shortcoming of "passive uptake" and allows for quick acquisition of robust SERS spectra from living C666, A431, and CA46 cancer cell lines in our study. Our study also shows that the silver nanoparticles are localized only in the cell cytoplasm for electroporation delivery, while for "passive uptake", the nanoparticles have gone beyond the cytoplasm and into the nucleus. However, the whole-cell detection SERS spectra using electroporation delivery are more reproducible than for "passive uptake", thus are favored for practical applications. As a result, the process of SERS detection is accelerated significantly and the data reproducibility is improved as well, demonstrating great potential for biomedical applications, such as for high-throughput cancer cell screening.
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http://dx.doi.org/10.1016/j.bios.2009.07.027DOI Listing
October 2009

Rapid delivery of silver nanoparticles into living cells by electroporation for surface-enhanced Raman spectroscopy.

Biosens Bioelectron 2009 Oct 3;25(2):388-94. Epub 2009 Aug 3.

Key Laboratory of Optoelectronic Science and Technology for Medicine, Ministry of Education and Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou 350007, China.

In current intracellular surface-enhanced Raman spectroscopy (SERS) measurements, gold or silver nanoparticles are delivered into living cells by "passive uptake". This procedure is time-consuming, could take up to several to twenties hours of incubation with nanoparticles in the culture medium. It is a less optimal method for certain applications such as high-throughput disease screening. Here, we present a method based on electroporation for fast delivery of silver nanoparticles into living cells for intracellular SERS spectroscopy. This new method for nanoparticle delivery averts the shortcoming of "passive uptake" and allows for quick acquisition of robust SERS spectra from living C666, A431, and CA46 cancer cell lines in our study. Our study also shows that the silver nanoparticles are localized only in the cell cytoplasm for electroporation delivery, while for "passive uptake", the nanoparticles have gone beyond the cytoplasm and into the nucleus. However, the whole-cell detection SERS spectra using electroporation delivery are more reproducible than for "passive uptake", thus are favored for practical applications. As a result, the process of SERS detection is accelerated significantly and the data reproducibility is improved as well, demonstrating great potential for biomedical applications, such as for high-throughput cancer cell screening.
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http://dx.doi.org/10.1016/j.bios.2009.07.027DOI Listing
October 2009

Fluorescence imaging to assess the matrix metalloproteinase activity and its inhibitor in vivo.

J Biomed Opt 2008 Jan-Feb;13(1):011006

Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Wuhan 430074, China.

Matrix metalloproteinases (MMPs) are a kind of secretory proteinases. Degradation of the extracellular matrix (ECM) by MMPs enhances tumor invasion and metastasis. To monitor MMPs activity and assess the MMP inhibitor effects in vivo, we constructed a plasmid that encoded a secretory fluorescent sensor named DMC (DsRed2-MSS-CFP expressed from pDisplay vector) that DsRed2 and cyan fluorescent protein (CFP) linked by MMP substrate site (MSS). MDA-MB 435s cells highly expressing endogenetic secretory MMP were transfected with the DMC plasmid so that the DMC could be cleaved by endogenetic MMP and the fluorescence ratio of DsRed2 to CFP was decreased. Treating the cells with GM6001, an MMP inhibitor, blocked the cleavage of DMC and caused an increase of the DsRed2/CFP ratio. The same result was achieved by using an in vivo tumor model that stable DMC-expressing MDA-MB 435s cells inoculated onto the chorioallantoic membrane of developing chick embryos to form primary tumors on the membrane. Thus, the fluorescent sensor DMC is able to sensitively monitor MMP activity and assess MMP inhibitors for anticancer research in vivo. This proves a novel method to efficiently screen and assess the anticancer drug MMP inhibitor in living cells and in vivo tumor models.
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http://dx.doi.org/10.1117/1.2830659DOI Listing
June 2008
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