That is precisely the kind of capability needed to capitalize on the new avenues of research that have been opened up by the 15-year-plus effort to sequence the human genome. DNA is the blueprint of all living creatures.
But, just as the blueprint of a building is much simpler than the actual structure, so too DNA is far simpler than the myriad of molecules that make up living bodies. As a result, scientists need powerful new methods to study the actual behavior of all these molecules, particularly how they work together.
The new method is called back-scattering interferometry (BSI). By shining a red laser like those used in barcode scanners into a microscopic, liquid-filled chamber where two kinds of molecules are mixed, the instrument can measure the strength with which they react, even when the interactions are extremely weak. In fact, the researchers have demonstrated that it is sensitive enough to detect the process of protein folding, they report in the Sept. 21, 2007 issue of the journal Science.
“Molecular interactions are the very heart of biology,” says Professor of Chemistry Darryl J. Bornhop, who headed the 12-year development process. “Pharmaceuticals depend on reactions between proteins and small molecules or between pairs of proteins or between interactions between RNA and DNA or pairs of DNA molecules. So the ability to measure how that happens is very advantageous.”
The members of the Bornhop research team are post doctoral students Joey Latham and Dmitry Markov; graduate student Amanda Kussrow; Henrik Sorenson, who is now at the Risø National Laboratory in Denmark; and Senior Research Associate Richard Jones.
The method represents an entirely new application of interferometry, a powerful technique that combines light from multiple sources to make precise measurements. Interferometry is used in everything from astronomy to holography to geodetic surveys to inertial navigation.
The equipment required for the new biosensor is surprisingly modest: a helium-neon laser like those used in grocery store scanners, a mirror, a CCD detector like those used in digital cameras and a special glass microfluidic chip. The chip contains a channel about one fiftieth the size of a human hair. There is a “Y” at one end that allows the researchers to inject two solutions simultaneously, each containing a different kind of molecule. It is followed by a serpentine section that mixes the two.
Finally, there is a straight observation section where the interactions are measured. An unfocused laser beam is directed through the channel at this point. The beam is reflected back and forth inside the channel about 100 times. Each time the light beam strikes the channel some of the light is transmitted back up to the mirror where it is directed to the detector. There it forms a line of alternating light and dark spots called an interference pattern.
It turns out that the interference pattern is very sensitive to what the molecules are doing. If the molecules begin sticking together, for example, the pattern begins to shift. The stronger the binding force between the molecules, the larger the shift. This allows the system to measure interaction forces that vary a million-fold. That includes the entire range of binding forces found in living systems.
The reason the system works so well is still something of a mystery. The researchers know that it responds to minute changes in the index of refraction, which is a measure of how fast the light travels through the liquid in the chamber compared to its speed in a vacuum. They suspect that it has to do with the rearrangement in the water molecules that cover the surface of the proteins: When two proteins react they squeeze the water molecules out of the area where they bind together. This displacement changes the density of the liquid slightly which, in turn, alters its index of refraction.
BSI has some potential cost advantages compared to current techniques. “The price of the equipment required for BSI is modest and the entire system could easily be miniaturized and integrated with ‘lab on a chip’ systems,” says Bornhop. It is also easy to adapt for high-throughput operation: processing hundreds or thousands of different samples at the same time, he says.
Vanderbilt has applied for and received two patents on the process and has several other patents pending. The university has issued an exclusive license to develop the technology to Molecular Sensing, Inc. Bornhop is one of the founders of the start-up and serves as its chief scientist. The company plans on completing a prototype system this fall.
Vanderbilt University is a private research university of approximately 6,300 undergraduates and 4,600 graduate and professional students. Founded in 1873, the University comprises 10 schools, a public policy institute, a distinguished medical center and The Freedom Forum First Amendment Center. Vanderbilt, ranked as one of the nation’s top universities, offers undergraduate programs in the liberal arts and sciences, engineering, music, education and human development, and a full range of graduate and professional degrees.
Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie
Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
20.09.2017 | Life Sciences
20.09.2017 | Power and Electrical Engineering
20.09.2017 | Physics and Astronomy