Thursday, December 25, 2008

Next Generation Microscopy: Goodbye Purple Fingers - No Stain Microscopy

Twenty years ago when I took Microbiology I learned about staining. Tissues had to be stained in order to 'see' the cells and cell organelles. Under a light microscope it all looks clear or pinkish and transparent. Add a couple of drops (or micro drops) of a certain dark stain would attach to the walls of the cell or organelle and then * wa-la* Contrast.

And for some reason all of the important stains were blue, hence the reference to blue fingers because you get some on your hands, lab coat, apron, table, etc.
Example stains include Methylene Blue Stain, Methyl Blue Stain,Indigo Stain....

and my time favorite, because it was the first staining technique I learned, was Crystal Violet or Methyl Violet used to differentiate Gram Negative Bacteria from Gram Positive Bacteria.
Microbiology lab was the first lab I took that made me feel so empowered. Lab was twice a week and I never minded staying for the whole time. It was hands-on learning and application of stuff I was learning in the class. I was holding a vial of something putrid and I was going to figure out what it was with stain and petri dishes. I felt like MacGyver. Do my pre-med, biology, chemistry, and biochem majors feel me? Aaah memories. My blue fingers were a badge of honor (and I didn't bite my nails much that semester.) But alas, those days may be no more. Some super-duper microbiology genius has helped us see the invisible without stain. Read more about it below.

Repost of NSF Press Release 08-218

Microscopes have revolutionized the practice of science, especially in the fields of biology and medicine. Just a few hundred years ago, gaining the ability to study what was previously unobservable opened up an entirely new world. Today, imaging techniques remain indispensable to clinicians and researchers who regularly diagnose medical conditions and work to develop new treatments.

Test results can often take hours or even days because cells or tissues must be subjected to lengthy fixation and labeling processes, sometimes called staining, in order to visualize and distinguish cellular components. In addition to long processing times, staining procedures often include harsh treatments or conditions that alter the tissues themselves, making interpretation of results difficult.

A newly developed label-free imaging technique called stimulated Raman scattering (SRS) will likely revolutionize biomedical imaging in research and diagnostic laboratories. A team lead by Sunney Xie at Harvard University reported this new technique in the December 19 issue of Science.
"It is a big step forward in terms of biology," said Xie. "SRS is a powerful imaging modality with widespread applications on many fronts of biology and medicine. This work compliments an earlier technique we developed with funding from the National Science Foundation, adding a new imaging modality to the vibrational microscopy field."
The key to this new chemical imaging technique is the use of two lasers with different frequencies. Researchers visualize samples by tuning the laser frequencies to match the vibrational frequency of a specific chemical bond. Each type of molecule within a sample, including nutrients or drugs, is detectable at a unique frequency. By combining sample data collected at numerous frequencies, researchers can produce a high-resolution 3D image of the sample. SRS microscopy represents a big gain in biomedical imaging because it avoids labor-intensive sample preparation and autofluorescence, or "background noise", associated with traditional fluorescence microscopy.
Xie is enthusiastic about the ways in which SRS imaging will facilitate progress in many fields. "Applications of SRS imaging range from mapping distribution of small metabolite and drug molecules in cells and tissues to medical diagnosis of cancer. Neuroimaging is another exciting area of application."
Media Contacts
Lisa Van Pay, NSF (703) 292-8796 lvanpay (at)
Lily Whiteman, NSF (703) 292-8070 lwhitema (at)
Principal Investigator
X. Sunney Xie, Harvard University (617) 496-9925 xie(at)

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