24 research outputs found
SERS multiplexing of methylxanthine drug isomers via host-guest size matching and machine learning
Multiplexed detection and quantification of structurally similar drug molecules, methylxanthine MeX, incl. theobromine TBR, theophylline TPH and caffeine CAF, have been demonstrated via solution-based surface-enhanced Raman spectroscopy (SERS), achieving highly reproducible SERS signals with detection limits down to ∼50 nM for TBR and TPH, and ∼1 μM for CAF. Our SERS substrates are formed by aqueous self-assembly of gold nanoparticles (Au NPs) and supramolecular host molecules, cucurbit[n]urils (CBn, n = 7, 8). We demonstrate that the binding constants can be significantly increased using a host–guest size matching approach, which enables effective enrichment of analyte molecules in close proximity to the plasmonic hotspots. The dynamic range and the robustness of the sensing scheme can be extended using machine learning algorithms, which shows promise for potential applications in therapeutic drug monitoring, food processing, forensics and veterinary science
SERS-based detection of haptoglobin in ovarian cyst fluid as a point-of-care diagnostic assay for epithelial ovarian cancer
Purpose: To evaluate haptoglobin (Hp) in ovarian cyst fluid as a diagnostic biomarker for epithelial ovarian cancers (EOCs) using surface-enhanced Raman spectroscopy (SERS)-based in vitro diagnostic assay for use in an intraoperative setting. Methods: SERS-based method was used to detect and quantify Hp in archived ovarian cyst fluids collected from suspicious ovarian cysts and differentiate benign tumors from EOCs. The
diagnostic performance of SERS-based assay was verified against the histopathology conclusions and compared with the results of CA125 test and frozen sections. Results: Hp concentration present in the clinical cyst fluid measured by SERS was normalized to 3.3 mg/mL of standard Hp. Normalized mean values for patients with benign cysts were 0.65 (n=57) and malignant cysts were 1.85 (n=54), demonstrating a significantly (P<0.01) higher Hp in malignant samples. Verified against histology, Hp measurements using SERS had a sensitivity of 94% and specificity of 91%. Receiver operating characteristic curve analysis of SERS-based Hp measurements resulted in area under the curve of 0.966±0.03, establishing the robustness of
the method. CA125 test on the same set of patients had a sensitivity of 85% and specificity of 90%, while frozen section analysis on 65 samples had 100% sensitivity and specificity. Conclusion: With a total execution time of <10 minutes and consistent performance across different stages of cancer, the SERS-based Hp detection assay can serve as a promising intraoperative EOC diagnostic test.National Medical Research Council (NMRC), Singapore; Bio-Medical Research Council of Agency for Science, Technology and Research (A*STAR), and the NHIC Innovation to Develop (I2D
Identification of mycolic acid forms using surface-enhanced Raman scattering as a fast detection method for tuberculosis
Jayakumar Perumal,1 US Dinishm,1 Anne K Bendt,2 Agne Kazakeviciute,1,3 Chit Yaw Fu,1 Irvine Lian Hao Ong,4 Malini Olivo1 1Laboratory of Bio-optical Imaging, Singapore Bioimaging Consortium, Agency for Science, Technology, and Research (A*STAR), Singapore; 2Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore; 3Department of Statistical Science, University College London, London, UK; 4Matralix Pte Ltd, Singapore Background: Tuberculosis (TB) is the ninth leading cause of death worldwide and the leading cause from a single infectious agent, based on the WHO Global Tuberculosis Report in 2017. TB causes massive health care burdens in many parts of the world, specifically in the resource constrained developing world. Most deaths from TB could be prevented with cost effective early diagnosis and appropriate treatment.Purpose: Conventional TB detection methods are either too slow as it takes a few weeks for diagnosis or they lack the specificity and accuracy. Thus the objective of this study was to develop a fast and efficient detection for TB using surface enhanced Raman scattering (SERS) technique.Methods: SERS spectra for different forms of mycolic acids (MAs) that are both synthetic origin and actual extracts from the mycobacteria species were obtained by label-free direct detection mode. Similarly, we collected SERS spectra for γ-irradiated whole bacteria (WB). Measurements were done using silver (Ag) coated silicon nanopillar (Ag SNP) as SERS substrate.Results: We report the SERS based detection of MA, which is a biomarker for mycobacteria species including Mycobacterium tuberculosis. For the first time, we also establish the SERS spectral characterization of the three major forms of MA – αMA, methoxy-MA, and keto-MA, in bacterial extracts and also in γ-irradiated WB. We validated our findings by mass spectrometry. SERS detection of these three forms of MA could be useful in differentiating pathogenic and nonpathogenic Mycobacterium spp.Conclusions: We have demonstrated the direct detection of three major forms of MA – αMA, methoxy-MA, and keto-MA, in two different types of MA extracts from MTB bacteria, namely delipidated MA and undelipidated MA and finally in γ-irradiated WB. In the near future, this study could pave the way for a fast and efficient detection method for TB, which is of high clinical significance. Keywords: Mycobacterium tuberculosis, MTB, nontuberculosis mycobacteria, NTM, mycolic acid, MA, SERS, silver-coated silicon nanopillars, Ag SNPs, liquid chromatography mass spectrometry, LC-M
Nanosphere Templated Metallic Grating Assisted Enhanced Fluorescence
In this paper, enhanced fluorescence from a silver film coated nanosphere templated grating is presented. Initially, numerical simulation was performed to determine the plasmon resonance wavelength by varying the thickness of the silver film on top of a monolayer of 400 nm nanospheres. The simulation results are verified experimentally and tested for enhancing fluorescence from fluorescein isothiocyanate whose excitation wavelength closely matches with the plasmon resonance wavelength of the substrate with 100 nm silver film over nanosphere. The 12 times enhancement in the intensity is attributed to the local field enhancement in addition to the excitation of surface plasmon polaritons along the surface
Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer
Ghayathri Balasundaram,1,* Chris Jun Hui Ho,1,* Kai Li,2 Wouter Driessen,3 US Dinish,1 Chi Lok Wong,1 Vasilis Ntziachristos,3 Bin Liu,2 Malini Olivo1,41Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC), 2Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), Singapore; 3Institute of Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany; 4School of Physics, National University of Ireland, Galway, Ireland *These authors contributed equally to this work Abstract: Conjugated polymers (CPs) are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots) in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots) in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used as a contrast agent for molecular PA diagnostic imaging in various biomedical applications. Keywords: photoacoustic tomography, conjugated polymers, molecular imaging, breast cance
SERS-based detection of haptoglobin in ovarian cyst fluid as a point-of-care diagnostic assay for epithelial ovarian cancer
Jayakumar Perumal,1,* Aniza Puteri Mahyuddin,2,* Ghayathri Balasundaram,1,* Douglas Goh,1 Chit Yaw Fu,1 Agne Kazakeviciute,1,3 US Dinish,1 Mahesh Choolani,2 Malini Olivo1 1Laboratory of Bio-optical Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), Singapore; 2Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 3Department of Mathematics, Brunel University London, Uxbridge, UK *These authors contributed equally to this work Purpose: To evaluate haptoglobin (Hp) in ovarian cyst fluid as a diagnostic biomarker for epithelial ovarian cancers (EOCs) using surface-enhanced Raman spectroscopy (SERS)-based in vitro diagnostic assay for use in an intraoperative setting. Methods: SERS-based method was used to detect and quantify Hp in archived ovarian cyst fluids collected from suspicious ovarian cysts and differentiate benign tumors from EOCs. The diagnostic performance of SERS-based assay was verified against the histopathology conclusions and compared with the results of CA125 test and frozen sections. Results: Hp concentration present in the clinical cyst fluid measured by SERS was normalized to 3.3 mg/mL of standard Hp. Normalized mean values for patients with benign cysts were 0.65 (n=57) and malignant cysts were 1.85 (n=54), demonstrating a significantly (P<0.01) higher Hp in malignant samples. Verified against histology, Hp measurements using SERS had a sensitivity of 94% and specificity of 91%. Receiver operating characteristic curve analysis of SERS-based Hp measurements resulted in area under the curve of 0.966±0.03, establishing the robustness of the method. CA125 test on the same set of patients had a sensitivity of 85% and specificity of 90%, while frozen section analysis on 65 samples had 100% sensitivity and specificity. Conclusion: With a total execution time of <10 minutes and consistent performance across different stages of cancer, the SERS-based Hp detection assay can serve as a promising intraoperative EOC diagnostic test. Keywords: surface-enhanced Raman spectroscopy, haptoglobin, epithelial ovarian cancer, ovarian cyst fluid, point-of-care diagnostic
A cost-effective identification of tobacco alkaloids using porous Si SERS substrates for forensic and bioanalytical applications
Optimized Synthesis of PEG-Encapsulated Gold Nanorods for Improved Stability and Its Application in OCT Imaging with Enhanced Contrast
10.1007/s11468-012-9438-1Plasmonics82591-59