To create drugs capable of targeting some of the most devastating human diseases, scientists must first decode exactly how a cell or a group of cells communicates with other cells and reacts to a broad spectrum of complex biomolecules surrounding it.
But even the most sophisticated tools currently used for studying cell communications suffer from significant deficiencies. Typically, these tools can detect only a narrowly selected group of small molecules or, for a more sophisticated analysis, the cells must be destroyed for sample preparation. This makes it very difficult to observe complex cellular interactions just as they would occur in their natural habitat — the human body.
Georgia Tech researchers have created a nanoscale probe, the Scanning Mass Spectrometry (SMS) probe, that can capture both the biochemical makeup and topography of complex biological objects in their normal environment — opening the door for discovery of new biomarkers and improved gene studies, leading to better disease diagnosis and drug design on the cellular level. The research was presented in the July issue of IEE Electronics Letters.
The new instrument, a potentially very valuable tool for the emerging science of systems biology, may help researchers better understand cellular interactions at the most fundamental level, including cell signaling, as well as identifying protein expression and response to the external stimuli (e.g., exposure to drugs or changes in the environment) from the organ scale down to tissue and even the single cell level.
“At its core, disease is a disruption of normal cell signaling,” said Dr. Andrei Fedorov, a professor in Georgia Tech’s Woodruff School of Mechanical Engineering and lead researcher on the project. “So, if one understands the network and all signals on the most fundamental level, one would be able to control and correct them if needed. The SMS probe can help map all those complex and intricate cellular communication pathways by probing cell activities in the natural cellular environment.”
The SMS probe offers the capability to gently pull biomolecules (proteins, metabolites, peptides) precisely at a specific point on the cell/tissue surface, ionize these biomolecules and produce “dry” ions suitable for analysis and then transport those ions to the mass spectrometer (an instrument that can detect proteins present even in ultra-small concentrations by measuring the relative masses of ionized atoms and molecules) for identification. The probe does this dynamically (not statically), imaging the surface and mapping cellular activities and communication potentially in real time. In essence, in scanning mode, the SMS probe could create images similar to movies of cell biochemical activities with high spatial and temporal resolution.
The SMS probe can be readily integrated with the Atomic Force Microscope (AFM) or other scanning probes, and can not only image biochemical activity but also monitor the changes in the cell/tissue topology during the imaging.
“The probe potentially allows us to detect complex mechano-bio-electro-chemical events underlying cell communication, all at the same time!” Fedorov said. “The future work is in refinement of the idea and development of a versatile instrument that can be used by biological and medical scientists in advancing the frontiers of biomedical research.”
The key challenge for the Georgia Tech team, which includes Dr. Levent Degertekin, was to create a way for a mass spectrometer, the primary tool for studying proteins, to sample biomolecules from a small domain and do it dynamically, thus enabling biochemical imaging. The researchers had to find a way to pull the targeted molecules out of the sample, as if they were using virtual tweezers, and then transfer these molecules into a dry and electrically charged state suitable for mass spectrometric analysis.
The solution to the problem came from a trick related to the basic fluid mechanics of ionic fluids, as the researchers exploited strong capillary forces to confine fluid within a nanoscale domain of the probe inlet (enabling natural separation of liquid and gaseous environments) and then used the classical Taylor electrohydrodynamic focusing of the jets to produce charged ions, but in reverse (pull) rather than in a commonly-used forward (push) mode.
The Georgia Institute of Technology is one of the nation's premiere research universities. Ranked ninth among U.S. News & World Report's top public universities, Georgia Tech educates more than 17,000 students every year through its Colleges of Architecture, Computing, Engineering, Liberal Arts, Management and Sciences. Tech maintains a diverse campus and is among the nation's top producers of women and African-American engineers. The Institute offers research opportunities to both undergraduate and graduate students and is home to more than 100 interdisciplinary units plus the Georgia Tech Research Institute. During the 2004-2005 academic year, Georgia Tech reached $357 million in new research award funding. The Institute also maintains an international presence with campuses in France and Singapore and partnerships throughout the world.
Megan McRainey | EurekAlert!
Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons
The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
24.11.2017 | Physics and Astronomy
24.11.2017 | Health and Medicine
24.11.2017 | Earth Sciences