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Apparatus and Instrumentation for Single Molecule Spectroscopy



  • Rational drug design: relating the static structure and dynamic function of biomolecules
  • Single molecule DNA sequencing
  • Rational de novo design and directed evolution of enzymes
  • Nanoscale biosensing
  • Design, control, and improvement of basic industrial processes


  • Continuous laser source is more economical and user friendly than pulsed sources
  • Registers photon arrival times
  • High resolution
  • Allows research parameter expansion
  • Prevents data overload
  • Enables greater understanding of continuous molecular behaviour as well as reactive mechanisms like drug binding


Haw Yang and Lucas Watkins at Berkeley Lab have developed instrumentation and algorithms that expand and enhance the capabilities of single molecule spectroscopy.  The new inventions make strides towards establishing a quantitative relationship between the static structure and the dynamic function of biomolecules – a key relationship that needs to be better understood if rational drug design is to make significant advances.  The Berkeley Lab inventions could also be applied to the use of single molecule spectroscopy for nanoscale biosensing, single molecule DNA sequencing, and the rational de novo design and directed evolution of enzymes.  The mechanistic understanding of chemical reactivity that can be provided by high-resolution single molecule spectroscopy is essential for the design, control, and improvement of many basic industrial processes as well.

The Berkeley Lab researchers have invented a noninvasive technique for 3-D tracking of a single moving particle or molecule while providing concurrent spectroscopic readouts. The method employs a confocal setup to form an intensity gradient for Z-axis resolution. The researchers have demonstrated nanometer spatial resolution with submillisecond response time using near-infrared light scattering to track a gold nanoparticle. (Reference number IB-2079)


  • IB-2079: Published PCT Patent Application WO/2007/076491 available at Available for licensing or collaborative research.


Watkins, L. P., Yang, H., "Information Bounds and Optimal Analysis of Dynamic Single Molecule Measurements," Biophysical Journal 2004, 86, 4015-4029.
Watkins, L.P., Yang, H., "Detection of Intensity Change Points in Time-Resolved Single Molecule Measurements," J. Phys. Chem. 2005, 109, 617-628.

Cang, H., Rizvi, A.H., Wong, C.M., Yang, H., Su, Shan. "Confocal Three-Dimensional Tracking of a Single Nanoparticle with Concurrent Spectroscipic Readouts." Applied Physics Letter. 88, 223901. 2006

REFERENCE NUMBER: IB-2009, IB-2010, IB-2098, IB-2079

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