APPLICATIONS OF TECHNOLOGY:

• Biological assays
• Chemical analysis
• Chromatography
• Studies of fast processes, such as fluid mixing and rapid binding

ADVANTAGES:

• Ultrahigh time resolution for NMR imaging--about 2 ms (500 frames/sec)
• High spectral resolution across the entire chip, allowing for detailed analysis of the fluid and chip properties
• Non-invasive
• Allows for chemical-shift imaging across the entire chip
• Encoding can be performed in inhomogeneous fields
• Can be coupled with chromatographic applications

ABSTRACT:

Alexander Pines and Elad Harel of Berkeley Lab have devised a system to use magnetic resonance imaging on microfluidic devices that offers both high time resolution and high spectral resolution. Their powerful new technology overcomes previous fundamental limitations in MR techniques bringing MRI technology a step forward and achieving time resolution of about 2 ms, an order of magnitude higher than would be achieved without this method. The invention also represents a major improvement over current optical detection methods that do not provide detailed information on the chemical composition of the fluid.

For chromatography applications, the arrival time of different chemical species can be distinguished without sacrificing spectral resolution, a feature that had never been accomplished with NMR or MRI. This broadens the scope of liquid-chromatography NMR (LC-NMR), which typically has to stop the flow for sensitive detection. Currently, LC-NMR only performs spectroscopy; but, with this method, the separation of compounds can be imaged and the time of arrival (time-of-flight or TOF) recorded representing the first instance in which LC-NMR was successfully coupled to imaging.  

The key to the new system is combining remote detection, i.e., detection off the chip, with time "slicing" through the use of magnetic field gradients. Magnetic resonance imaging of the fluids is conducted in the detection coil after they exit the chip. The detector can be sliced into smaller "virtual" detectors, with each slice corresponding to a slice of time. Remote detection allows the system to maintain an acceptable level of sensitivity while also allowing for chemical-shift imaging.

Because the imaging gradient is also used in the encoding region on the chip, the system allows for the acquisition of time-resolved NMR spectra of fluid present at various locations across the microfluidic chip. It also provides information on multiple compounds such as their location on the chip and flow properties. With simple improvements in design and pulse sequences, the system may be able to achieve time resolutions of less than 100 m s.

STATUS:

• Published PCT Patent Application WO2009/029880 available at www.wipo.int. Available for licensing or collaborative research.

To learn more about licensing a technology from LBNL see http://www.lbl.gov/Tech-Transfer/licensing/index.html.

FOR MORE INFORMATION:

Pines A., and E. Harel, " Spectrally resolved flow imaging of fluids inside a microfluidic chip with ultrahigh time resolution ," Journal of Magnetic Resonance 193, 199 (2008).

E. Harel, "Magnetic resonance detection: spectroscopy and imaging of lab-on-a-chip," Lab on a Chip , published online 2008, DOI: 10.1039/b807036a

REFERENCE NUMBER: IB-2474

SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:

• Portable, High Resolution NMR/MRI in Inhomogeneous Fields, IB-2185
• Mobile Ex Situ High Resolution NMR and MRI, IB-1717
• Low-Field MRI with Improved Resolution and Portability Using Gradient Fields of Arbitrary Size, IB-2062
• Remote MNR/MRI Detection, IB-1771