Research Area A: Sensor Development

A2 – Tissue Differentiation using IR-Spectroscopy

During the proliferation of tumour cells the proportions of tissue components change which also yields changes in its optical characteristics. Thus the spectra of tumorous and healthy tissue differ and it is possible to distinguish them from one another. The spectroscopic examination of organic material has commonly been conducted with FTIR spectrometers, but they are gradually being replaced by modern IR-spectrometers that are based on the principle of attenuated total reflection.

Efficient Spectroscopic Measurements due to In-situ Applications

A successful tumour resection is defined by its completeness. Nowadays, in most surgeries the tissue is analyzed using the so-called frozen section technique, where the material is cryogenically frozen, cut into thin slices and stained with haematoxylin eosin (HE) for instance. Afterwards, the specimen is investigated using a microscope where spectroscopic measurements can be taken as well (e.g. hyperspectral imaging using FTIR spectrometers). The complete investigation can last up to 30 minutes and the results of the staining are worse and harder to interpret than those of histopathological inspections, in which the tissue slices are embedded in formalin as well. Hence this research training group aims to get rid of those disadvantages tracing a multimodal approach in which several sensor types are being developed and examined. Those sensors shall enable in-situ investigations, which means that the measurements are undertaken within the living body during surgery. The multimodal approach shall increase the reliability of the sensors due to mutual validation.

Main problems using the frozen section technique:

  • investigation time of approximately 30 minutes
  • bad staining results

The approach in this subproject covers the scope of infrared (IR) spectroscopy which is, together with Raman spectroscopy (subproject A3), the most suitable spectroscopy type in organic chemistry. The radiation energy of light stimulates the molecules in both cases and they start to vibrate. Their vibration frequencies can be gathered from the corresponding spectrum. In contrast to Raman spectroscopy, the IR spectroscopy usually uses polychromatic light with wavenumbers in the range of 4000-400 cm-1.

Microtome section of a bladder carcinoma organoid under an IR microscope. The red squares highlight the position and integration area of the IR spectroscopy.

Quantum Cascade Lasers as an Alternative Light Source

Measurements with conventional FTIR spectrometers use globars as a light source, which cover the whole mid-infrared spectrum. Previous work has shown that this abundance of signals is not necessary to distinguish between malignant and benign tissue spectra. That is why only a few suitable quantum cascade lasers shall be combined and used in one sensor.

This involves several advantages:

  • better signal-to-noise ratio
  • lower recording time
  • minimizing disruptive effects due to unwanted vibrations
IR spectra of the above mentioned bladder carcinoma organoids measured in reflection.

The first goal in this subproject is to find the best suited wavelengths to achieve the best distinguishing result. Therefore, the following approaches are examined:

  1. analysis of IR spectra from literature, simulations, and experiments
  2. data analysis using multivariate statistical methods (e.g. principal component analysis)
  3. use of neural networks

Sensor Implementation into an Endoscope

Another challenge is to develop a sensor that fits in an endoscope. Additionally, the measurement shall be undertaken in-situ which requires the measurement to be based on absorption or scattering of the tissue. An extremely suitable technique is the ATR spectroscopy which provides information on the absorbance of the investigated material by measuring the amount of totally reflected light. In principal, this sensor consists of a light source, a detector, and a crystal with a higher refractive index than the tissue.

Editors

This image showsFelix Fischer
M.Sc.

Felix Fischer

PhD Student A2

This image showsAlois Herkommer
Prof. Dr. rer. nat.

Alois Herkommer

Manager of Subprojects A1&A2

This image showsKarsten Frenner
Dr.

Karsten Frenner

Supervisor of Subproject A2

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