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Spatial resolution of tip-enhanced Raman spectroscopy – DFT assessment of the chemical effect

2016, Latorre, Federico, Kupfer, Stephan, Bocklitz, Thomas, Kinzel, Daniel, Trautmann, Steffen, Gräfe, Stefanie, Deckert, Volker

Experimental evidence of extremely high spatial resolution of tip-enhanced Raman scattering (TERS) has been recently demonstrated. Here, we present a full quantum chemical description (at the density functional level of theory) of the non-resonant chemical effects on the Raman spectrum of an adenine molecule mapped by a tip, modeled as a single silver atom or a small silver cluster. We show pronounced changes in the Raman pattern and its intensities depending on the conformation of the nanoparticle–substrate system, concluding that the spatial resolution of the chemical contribution of TERS can be in the sub-nm range.

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Single cell analysis in native tissue: Quantification of the retinoid content of hepatic stellate cells

2016, Galler, Kerstin, Requardt, Robert Pascal, Glaser, Uwe, Markwart, Robby, Bocklitz, Thomas, Bauer, Michael, Popp, Jürgen, Neugebauer, Ute

Hepatic stellate cells (HSCs) are retinoid storing cells in the liver: The retinoid content of those cells changes depending on nutrition and stress level. There are also differences with regard to a HSC’s anatomical position in the liver. Up to now, retinoid levels were only accessible from bulk measurements of tissue homogenates or cell extracts. Unfortunately, they do not account for the intercellular variability. Herein, Raman spectroscopy relying on excitation by the minimally destructive wavelength 785 nm is introduced for the assessment of the retinoid state of single HSCs in freshly isolated, unprocessed murine liver lobes. A quantitative estimation of the cellular retinoid content is derived. Implications of the retinoid content on hepatic health state are reported. The Raman-based results are integrated with histological assessments of the tissue samples. This spectroscopic approach enables single cell analysis regarding an important cellular feature in unharmed tissue.

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A manual and an automatic TERS based virus discrimination

2015, Olschewski, Konstanze, Kämmer, Evelyn, Stöckel, Stephan, Bocklitz, Thomas, Deckert-Gaudig, Tanja, Zell, Roland, Cialla-May, Dana, Weber, Karina, Deckert, Volker, Popp, Jürgen

Rapid techniques for virus identification are more relevant today than ever. Conventional virus detection and identification strategies generally rest upon various microbiological methods and genomic approaches, which are not suited for the analysis of single virus particles. In contrast, the highly sensitive spectroscopic technique tip-enhanced Raman spectroscopy (TERS) allows the characterisation of biological nano-structures like virions on a single-particle level. In this study, the feasibility of TERS in combination with chemometrics to discriminate two pathogenic viruses, Varicella-zoster virus (VZV) and Porcine teschovirus (PTV), was investigated. In a first step, chemometric methods transformed the spectral data in such a way that a rapid visual discrimination of the two examined viruses was enabled. In a further step, these methods were utilised to perform an automatic quality rating of the measured spectra. Spectra that passed this test were eventually used to calculate a classification model, through which a successful discrimination of the two viral species based on TERS spectra of single virus particles was also realised with a classification accuracy of 91%.

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Deep learning-based classification of blue light cystoscopy imaging during transurethral resection of bladder tumors

2021, Ali, Nairveen, Bolenz, Christian, Todenhöfer, Tilman, Stenzel, Arnulf, Deetmar, Peer, Kriegmair, Martin, Knoll, Thomas, Porubsky, Stefan, Hartmann, Arndt, Popp, Jürgen, Kriegmair, Maximilian C., Bocklitz, Thomas

Bladder cancer is one of the top 10 frequently occurring cancers and leads to most cancer deaths worldwide. Recently, blue light (BL) cystoscopy-based photodynamic diagnosis was introduced as a unique technology to enhance the detection of bladder cancer, particularly for the detection of flat and small lesions. Here, we aim to demonstrate a BL image-based artificial intelligence (AI) diagnostic platform using 216 BL images, that were acquired in four different urological departments and pathologically identified with respect to cancer malignancy, invasiveness, and grading. Thereafter, four pre-trained convolution neural networks were utilized to predict image malignancy, invasiveness, and grading. The results indicated that the classification sensitivity and specificity of malignant lesions are 95.77% and 87.84%, while the mean sensitivity and mean specificity of tumor invasiveness are 88% and 96.56%, respectively. This small multicenter clinical study clearly shows the potential of AI based classification of BL images allowing for better treatment decisions and potentially higher detection rates.