Navigation Links
Seeing previously invisible molecules for the first time
Date:10/23/2009

A team of Harvard chemists led by X. Sunney Xie has developed a new microscopic technique for seeing, in color, molecules with undetectable fluorescence. The room-temperature technique allows researchers to identify previously unseen molecules in living organisms and offers broad applications in biomedical imaging and research.

The scientists' results are published in the Oct. 22 issue of Nature. Partial funding for the project was provided by the National Science Foundation (NSF).

Fluorescence is a phenomenon in which an electron in a molecule absorbs energy from light and moves to a higher energy level or excited state. The energy of the light is contained in a unit called a photon.

After a very brief stay at the excited state, the electron returns to its previous energy level, or ground state, by emitting a new photon. The energy of the released photon is discharged in wavelengths of detectable visible light lasting only a few billionths of a second.

Many biologically important colored molecules such as hemoglobin--an oxygen-transport protein in red blood cells--absorb light but do not fluoresce. Instead, the electrons in these molecules release their additional but transient energy by converting it to heat.

"Since these molecules do not fluoresce, they have literally been overlooked by modern optical microscopes," Xie said.

To detect non-fluorescent molecules in biological systems, Xie and his team developed a new type of microscopy based on stimulated emission.

Stimulated emission was first described by Albert Einstein in 1917, and was the basis for today's lasers. In a nutshell, it is a process by which an excited-state electron, perturbed by a photon having the correct energy, drops to its ground state producing an additional photon.

Xie's new microscopic technique generates and records a stimulated emission signal by using two carefully timed input and output pulse trains. In the input pulse train, a modulator switches the intensity of the excitation beam on and off at five megahertz, or MHz. The modulation creates a stimulated emission signal at the same frequency. Each train has an incredibly short pulse duration of approximately 200 femtoseconds. A femtosecond is equal to one billionth of one millionth of a second or 10-15 seconds.

The signal produced by the non-fluorescent molecules provides a highly sensitive image of previously "invisible" molecules.

One of the several possible applications of the scientists' invention is mapping in color the delivery of non-fluorescent drugs to their target cells. Another possible use is imaging tiny structures such as blood vessels including individual red blood cells and single capillaries (see images).

The structure and hemoglobin-dynamics of blood vessels play a major role in many biomedical processes. Two example processes are the transition of tumors from a dormant to malignant state and oxygen delivery in the brain.

Current established imaging technologies like MRIs and CT scans either lack the spatial resolution needed to resolve individual capillaries or require external contrast agents.

Fluorescent labels such as the green fluorescent protein, or GFP, are extensively used for observing the activity of biomolecules and distinguishing target molecules in a cell. The GFP labeling technique provides well-defined images. However, the bulky protein can disturb delicate biological pathways, especially when it is larger than the biomolecules it is illuminating.

Xie's team mapped the delivery of a non-fluorescent drug molecule and imaged blood vessels without fluorescent labels.

Their new technique is also capable of imaging non-fluorescent proteins in cells of live Escherichia coli bacteria.

"While earlier studies made use of similar pump-probe experiments to provide images of fluorescent molecules with spatial resolution comparable to that of confocal fluorescence microscopy and high temporal resolution, this study, for the first time, makes use of stimulated emission microscopy to image non-fluorescent molecules," said Zeev Rosenzweig, a program director in the NSF Division of Chemistry.

Although potential photo-damage, and the complexity and cost of the system still need to be addressed for the technique to gain wide applicability, "there is no doubt that the study provides a unique way to image a wide range of molecules currently inaccessible to today's state-of-the-art optical microscopes," notes Rosenzweig.

"This is just the beginning," added Xie. "Many interesting applications of this new imaging modality are forth coming."


'/>"/>

Contact: Jennifer A. Grasswick
jgrasswi@nsf.gov
703-292-4972
National Science Foundation
Source:Eurekalert

Related biology news :

1. Seeing the tree from the forest: Predicting the future of plant communities
2. Seeing stem cells helps in fight against peripheral arterial disease
3. Seeing through the skin
4. Crystal (eye) ball: Study says visual system equipped with future seeing powers
5. Seeing Alzheimers amyloids
6. Genome duplication responsible for more plant species than previously thought
7. Oscar Pistorius: Previously confidential study results released on amputee sprinter
8. Lower increases in global temps could lead to greater impacts than previously thought, study finds
9. Evolutionary process more detailed than previously believed, study shows
10. Nations that sow food crops for biofuels may reap less than previously thought
11. Whispering bats are 100 times louder than previously thought
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... 2017 Today HYPR Corp. , leading ... component of the HYPR platform is officially FIDO® ... security architecture that empowers biometric authentication across Fortune 500 ... secured over 15 million users across the financial services ... home product suites and physical access represent a growing ...
(Date:4/3/2017)...  Data captured by IsoCode, IsoPlexis Corporation,s ... statistically significant association between the potency of ... objective response of cancer patients post-treatment. The ... cancer patients will respond to CAR-T cell ... to improve both pre-infusion potency testing and cell ...
(Date:3/30/2017)... , March 30, 2017 Trends, opportunities ... (physiological and behavioral), by technology (fingerprint, AFIS, iris recognition, ... recognition, and others), by end use industry (government and ... immigration, financial and banking, and others), and by region ... , Asia Pacific , and ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... Tampa Bay, Florida (PRWEB) , ... October 11, ... ... Food and Drug Administration (FDA) has granted orphan drug designation to SBT-100, its ... antibody (sdAb) for the treatment of osteosarcoma. SBT-100 is able to cross the ...
(Date:10/10/2017)... ... ... Dr. Bob Harman, founder and CEO of VetStem Biopharma, Inc. ... event entitled “Stem Cells and Their Regenerative Powers,” was held on August 31st, ... was joined by two human doctors: Peter B. Hanson, M.D., Chief of Orthopedic Surgery, ...
(Date:10/10/2017)... (PRWEB) , ... October 10, 2017 , ... ... recipients of 13 prestigious awards honoring scientists who have made ... in a scheduled symposium during Pittcon 2018, the world’s leading conference and exposition ...
(Date:10/9/2017)... ... 2017 , ... The Giving Tree Wellness Center announces the ... of consumers who are incorporating medical marijuana into their wellness and health regimens. ... operators of two successful Valley dispensaries, The Giving Tree’s two founders, Lilach Mazor ...
Breaking Biology Technology: