Researchers apply NMR/MRI to microfluidic chromatography

 

By pairing an award-winning remote-detection version of NMR/MRI technology with a unique version of chromatography specifically designed for microfluidic chips, researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) have opened the door to a portable system for highly sensitive multi-dimensional chemical analysis that would be impractical if not impossible with conventional technologies.

Alexander Pines, a faculty senior scientist in Berkeley Lab's Materials Sciences Division and the Glenn T. Seaborg Professor of Chemistry at the University of California (UC) Berkeley, is one of the word's foremost authorities on NMR (nuclear magnetic resonance) and its daughter technology, MRI (Magnetic Resonance Imaging). In this latest development, he led a collaboration in which a remote detection NMR/MRI technique that can rapidly identify the chemical constituents of samples in microfluidic "lab-on-a-chip" devices was used to perform analyses in a microscale monolithic chromatograph column.

"We have presented the first demonstration that a monolithic chromatograph column can be used to separate small molecules on a timescale that is compatible with NMR/MRI detection, an important first step to portable chromatographic devices," says Vikram Bajaj, a project scientist in the Pines' group who is the corresponding author of a paper describing this work in the journal Analytical Chemistry.

The Analytical Chemistry paper is titled "Remotely Detected NMR for the Characterization of Flow and Fast Chromatographic Separations Using Organic Polymer Monoliths." Co-authoring the paper with Pines and Bajaj were Thomas Teisseyre, Jiri Urban†, Nicholas Halpern-Manners, Stuart Chambers and Frantisek Svec.

Chromatography is one of the indispensable tools of chemistry. By dissolving sample into a fluid – called the "mobile phase" – and flushing it through a solid medium – called the "stationary phase" - chemists can separate the sample's constituent chemical species - called analytes – for identification and measurement, as well as for purification purposes. Analytes will be separated on the basis of how fast each individual species diffuses through the stationary phase.

"The coupling of our remote NMR/MRI technology with monolithic chromatography columns in a microfluidic chip enables us to obtain high resolution, velocity-encoded images of a mobile phase flowing through the stationary phase," Bajaj says. "Our technique provides both real-time peak detection and chemical shift information for small aromatic molecules, and demonstrates the unique power of magnetic resonance, both direct and remote, in studying chromatographic processes."

The coupling of remote NMR/MRI to chromatography was made possible by the polymer monolithic column, a technology developed by Analytical Chemistry paper co-author Frantisek Svec, a chemist who directs the Organic and Macromolecular Synthesis facility at Berkeley Lab's Molecular Foundry, a DOE nanoscience center. In conventional chromatography, the stationary phase column is typically filled with porous polymer beads or some other discrete medium whose physical or chemical properties modulate the diffusion rates of analytes passing through. In Svec's stationary phase, a chromatography column is filled with a monolithic solid polymer – meaning it is a single, continuous piece - that is perforated throughout with nanoscopic pores.

"Polymer monoliths as a separation media can be compared to a single large particle that does not contain inter-particular voids," Svec says. "As a result, all the mobile phase must pass through the stationary phase as convective flow rather than diffusion during chromatographic processes. This convective flow greatly accelerates the rate of analyte separation."

The remote NMR/MRI technology whose development was led by Pines won a 2011 R&D 100 Award. These awards, known as the "Oscars of Innovation," recognize the year's 100 most significant proven technological advances. Through a combination of remote instrumentation, JPEG-style image compression algorithms and other key enhancements, this remote NMR/MRI technology can zoom in on microscopic objects of interest within a sample flowing through the columns of a microfluidic chip with unprecedented spatial and time resolutions.

"Our remote NMR/MRI technology enables time-resolved imaging of multi-channel flow, dispenses with the need for large and expensive magnets for analysis, allows us to analyze complex and unprocessed mixtures in one pass, and adds portability to NMR/MRI," Bajaj says.

The key to the success of remote NMR/MRI technology is the decoupling of the NMR/MRI signal encoding and detection phases. NMR/MRI signals arise from a property found in the atomic nuclei of almost all molecules called "spin," which makes the nuclei act as if they were bar magnets with poles that point either "north" or "south." Obtaining an NMR/MRI signal from a sample depends upon an excess of nuclear spins pointing in one direction or the other. In a conventional NMR/MRI set-up, in which the signal encoding and detection phases take place within one machine, this require the presence of a powerful external magnetic field. The remote NMR/MRI technology developed by Pines and his group, in which NMR?MRI signal encoding and detection are carried out independently, can detect NMR/MRI signals without the need of such a strong magnet, yet it still provides the same outstanding sensitivity of conventional NMR/MRI.

"With our remote NMR/MRI technology and the polymer monoliths of Frank Svec's group, we were able to look inside optically opaque microfluidic columns and measure the velocity of the flowing fluid during a chromatographic separation," Bajaj says. "We were also able to demonstrate in-line monitoring of chromatographic separations of small molecules at high flow rates."

Results using the remote NMR/MRI technique with the polymer monoliths showed a much better ability to discriminate between different analytes at the molecular level, Bajaj says, than comparable analysis using spectrometry based on either mass or optical properties. This paves the way for multidimensional analysis, in which the result of a chromatographic separation would be encoded into an NMR/MRI signal by charge, size or some other factor and stored. The encoded fluid would then be run through a second separation and those results would also be encoded into an NRM/MRI signal and stored.

"This would allow us to create a multidimensional chromatography experiment that does not require the fluid volume to be physically partitioned," Bajaj says. "The fluid would, quite literally, be partitioned in the magnetic degrees of freedom instead."

Provided by Lawrence Berkeley National Laboratory (news : web)

Same rules apply to some experimental systems regardless of scale

New experiments show that common scientific rules can apply to significantly different phenomena operating on vastly different scales.

The results raise the possibility of making discoveries pertaining to phenomena that would be too large or impractical to recreate in the laboratory, said Cheng Chin, associate professor in physics and the James Franck Institute at the University of Chicago. Chin and associates Chen-Lung Hung, Xibo Zhang and Nathan Gemelke will publish their results in the Feb. 10, 2011 issue of the journal Nature.

Chin aspires to simulate the impossibly hot conditions that followed the big bang, during the earliest moments of the universe, by using an ultracold vacuum chamber in his laboratory. "It's fascinating to think about all these connections," he said.

The UChicago experiments demonstrate the validity of two widely discussed topics in the physics community today: scale invariance and universality.

Theoretical physicist Lev Pitaevskii had predicted that scale invariance would apply to a two-dimensional, cold-atom gas in 1997. Scale invariance means that the properties of a given phenomenon will remain the same, no matter how much its size is expanded or contracted. This contrasts sharply the three-dimensional world of everyday life, where dynamics change dramatically.

In the biological world, for example, scale invariance does not apply to complex organisms like humans, but exists in simple biological structures like nautilus shells, ferns and even broccoli. In physics, special cases also exist that exhibit scale invariance. Fractal structures have been observed in nature, which manifest similar structures whether magnified 10, 1,000 or a million times.

"There are only a few systems in nature that can display this kind of scale invariance, and we have shown that our two-dimensional system belongs to this very special class," Chin explained. "Once you identify these special cases and see how they are all linked together, then you can bring all these physical phenomena under the same umbrella," Chin said. "Now they can be fully described using the same language."

Exotic transformation

The universality concept applies to matter that undergoes smooth phase transitions. In the physics of everyday life, a phase transition occurs when water freezes to ice on a cold winter day. The phase transition in the UChicago experiment is more exotic: In the experiment, cesium atoms transform from a gas to a superfluid, a form of matter that exists only at temperatures of hundreds of degrees below zero.

Theoretical physicists in the early 1970s predicted that weakly interacting two-dimensional gases would exhibit similar behaviors under a variety of conditions as they neared the critical point of phase transition. Their prediction has remained unverified until now.

In their experiment, the UChicago researchers super-cooled thousands of cesium atoms to 10 nano-Kelvin, billionths of a degree above absolute zero (-459.67 degrees Fahrenheit), then loaded them into a pancake-like laser trap. The trap simulated a two-dimensional system by restricting the atoms' motion vertically but allowed a significant degree of horizontal freedom.

Chin's team was able to control the properties of this cold-atom gas system to make it non-interacting, weakly interacting or strongly interacting and then compared the results.

"At the same time, we can prepare the two-dimensional system at different sizes and also at different temperatures," Chin said. They could adjust the size parameters from 10 to 100 microns (a human hair is approximately 50 microns in diameter), and the temperature parameters from 10 to 100 nano-Kelvin.

Their experiment showed that no matter how they changed these three parameters, just one general description could characterize the resulting dynamics.

"There's a strong reason to believe that this kind of scale invariance can be extrapolated and on a more fundamental level can be mapped to other types of two-dimensional systems," Chin said. "The bigger question is whether our observation can shed light on other complex phenomena in nature. So our next step will be to explore going beyond two-dimensional systems."

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Chicago.

Journal Reference:

Chen-Lung Hung, Xibo Zhang, Nathan Gemelke, Cheng Chin. Observation of scale invariance and universality in two-dimensional Bose gases. Nature, 2011; DOI: 10.1038/nature09722

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