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
At last, butterflies get a bigger, better evolutionary tree
16.02.2018 | Florida Museum of Natural History
New treatment strategies for chronic kidney disease from the animal kingdom
16.02.2018 | Veterinärmedizinische Universität Wien
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).
Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
16.02.2018 | Information Technology
16.02.2018 | Health and Medicine
16.02.2018 | Physics and Astronomy