Cerebrospinal fluid (CSF) of the central nervous system disseminates numerous cells, proteins, microparticles, and DNA as potential biomarkers of many diseases and therapy efficacy.
For example, circulating tumor cells are a sign for metastatic cancer, bacteria can reveal an infectious meningitis or encephalitis, erythrocytes indicate a trauma, and tau-protein is a biomarker for Alzheimer’s disease.
However, current methods for detecting biomarker in CSF are far from ideal. A main drawback is that the tests are performed in vitro, and their sensitivity is limited by the sample volume. Rare circulating biomarkers such as tumor cell at the stage of latent metastasis remain undetectable. Furthermore, cytology is a quite subjective method depending on the experience of the laboratory technicians. Yet, other current methods show even higher false-negative results than cytology.
The problem could be solved by examining a larger volume. Ekaterina I. Galanzha and a team from the University of Arkansas for Medical Sciences thought to examine the whole CSF volume. To pursue this objective, they developed a method using in vivo photoacoustic flow cytometry (PAFC) for ultrasensitive detection of cells and nanoparticles in CSF. During PAFC, non-radiative relaxation of absorbed laser energy into heat leads to thermoelastic generation of sound.
PAFC is not sensitive to light scattering or autofluorescence and provides higher sensitivity and resolution in deeper tissue than other optical modalities. When CSF is irradiated through skin, photoacoustic waves from individual cells can be detected with an ultrasound transducer attached to the tissue over ventricles or spinal cord. The method is noninvasive for normal tissues as it operates with laser energy at levels that are safe for humans.
To extend diagnostic significance, PAFC was integrated with photothermal scanning cytometry/microscopy ex vivo using label-free mode as well as molecular targeting with low-toxicity bioconjugated nanoparticles. In photothermal thermal-lens schematic, laser induced temperature-dependent variation of the refractive index around absorbing zones is optically detected.
Contrast can be enhanced by labeling cells or molecules of interest with specifically binding nanoparticles such as gold nanorods. In the experiments, two types of nanorods were used with different absorption maxima for two color labeling.
In the CSF of tumor-bearing mice, the researchers molecularly detected in vivo circulating tumor cells before the development of breast cancer brain metastasis with 20-times higher sensitivity than with current assays. For the first time, they demonstrated assessing three pathways – blood, lymphatic, and CSF – of circulating tumor cells dissemination, tracking nanoparticles in CSF and their imaging ex vivo. The scientists were able to count leukocytes, erythrocytes, melanoma cells, and bacteria in label-free CSF samples.In addition, they could image intracellular cytochromes, hemoglobin, melanin, and carotenoids, respectively, by labeling with specific binding gold nanorods.
Taking into account the safety of PAFC, the researchers expect its translation for use in humans to improve disease diagnosis beyond conventional detection limits. (Text contributed by K. Maedefessel-Herrmann)Nedosekin, D.A., et al; J. Biophotonics 6(6-7), 523-533 (2013); DOI 10.1002/jbio.201200242
http://onlinelibrary.wiley.com/doi/10.1002/jbio.201200242/abstractWiley-VCH Verlag GmbH & Co. KGaA
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Health and Medicine
29.03.2017 | Earth Sciences
29.03.2017 | Trade Fair News