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
Historical rainfall levels are significant in carbon emissions from soil
30.05.2017 | University of Texas at Austin
3D printer inks from the woods
30.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Scientists have developed a new method of characterizing graphene’s properties without applying disruptive electrical contacts, allowing them to investigate both the resistance and quantum capacitance of graphene and other two-dimensional materials. Researchers from the Swiss Nanoscience Institute and the University of Basel’s Department of Physics reported their findings in the journal Physical Review Applied.
Graphene consists of a single layer of carbon atoms. It is transparent, harder than diamond and stronger than steel, yet flexible, and a significantly better...
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
30.05.2017 | Life Sciences
30.05.2017 | Life Sciences
30.05.2017 | Physics and Astronomy