Non-Contact Total Emission Detection Methods for Multiphoton Microscopy: Improved Image Fidelity and Biological Sample Analysis

The technology offered for licensing and for further development is in the field of multiphoton microscopy (MPM). More specifically, the invention pertains to optical designs that can enhance and extend the capabilities of MPM in spectral imaging of biological samples. The unique design of the light collection and the detection optics maximizes the collection of emitted light, thus increasing the signal and hence the signal-to-noise ratio (SNR). Improvement in image fidelity will result in improved analysis of biological samples and thus will favorably impact medical research and possibly clinical diagnosis. The present technology is a further improvement on the TED (Total Emission Detection) technology, first disclosed by Dr. Robert Balaban et al. at the NIH in 2006 and claimed in US Patent 7,667,210 (issued February 23, 2010). The earlier NIH TED technology proposed an optical design based on enveloping the entirety of a small sample in a parabolic mirror/condenser combination so light emanated by a sample in all directions is redirected to the detector. The present technology further expands the capabilities of TED as its unique design employing parabolic, toric and conic mirrors ensures maximum light collection from large samples in cases where there is only access to one side of the tissues (e.g., in vivo or ex vivo). This is accomplished by the redirection of all attainable light (i.e., light escaping the tissue or a whole animal in the epi and sideway directions) to the detector.

Potential Commercial Applications: Competitive Advantages:
  • Tissue and cell analysis in biomedical research
  • Potential applications in clinical diagnostics
  • Increased signal-to-noise ratio
  • Enhanced image resolution due to SNR
  • Improved analytical capabilities
  • Non-contact
  • May readily be adaptable to commercial microscopes

Development Stage:
  • In vitro data available
  • Prototype

Related Invention(s):


Jay Knutson (NHLBI)  ➽ more inventions...

Intellectual Property:
PCT Pat: 8,759,792 issued 2014-06-24
US Application No. 61/224,772 filed on 2009-07-10
US Application No. 13/383,248 filed on 2010-07-12

Combs CA, et al. PMID 18045327
Combs CA, et al. PMID 24251437
Combs CA, et al. PMID 21118209

Collaboration Opportunity:

The NHLBI Laboratory of Molecular Biophysics is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize an enhanced method of multiphoton microscopy that is suitable for the spectral imaging of biological samples. Please contact Brian W. Bailey, Ph.D. at for more information.

Licensing Contact:
Brian Bailey, Ph.D.
Phone: 301-594-4094

OTT Reference No: E-236-2009-0
Updated: Jul 8, 2014