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EUV Laser Enables Nanoscale, 3D Imaging of Cells

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A mass-spectral imaging system that integrates an EUV laser has enabled the mapping of cellular compositions in 3D, allowing researchers to watch how cells respond to medications at the nanoscale.

In addition to observing how cells respond to new drugs, researchers from Colorado State University said the technology could be used the sources of pathogens propagated for bioterrorism, and to new methods for overcoming antibiotic resistance among patients with surgical implants.

An instrument built at Colorado State University lets scientists map cellular composition in three dimensions at the nanoscale, allowing researchers to watch how cells respond to new medications at the most minute level ever observed. Courtesy of Jason Russell/Colorado State University.

The instrument comprises mass-spectral imaging technology and an extreme ultraviolet (EUV) laser. The EUV beam produces in a tiny stream of plasma that is very hot and dense, and which acts as a gain medium for generating EUV laser pulses.

The laser was focused to shoot into a cell sample, guided through chambers using mirrors and lenses that focused it down to a diameter of less than 100 nm. In a chamber at the far side of the spectrometer, the laser hit a sample cell placed with the aid of a microscope. Each time the laser drilled a tiny hole, ions evaporated from the cell surface. These ions were then separated and identified, allowing scientists to determine chemical composition.

A sample has to be perfectly positioned in the instrument to gain proper readings.
A sample has to be perfectly positioned in the instrument to gain proper readings. Courtesy of Colorado State University.

Once the laser drilled a miniscule hole in the cell, charged ions emitted after the tiny explosion were drawn into a side tube using electrostatic fields. The larger mass the charged particle had, the slower it moved down the tube; the time it took an ion to reach a detector gave scientists information about its mass.

A set of pumps created high vacuum that sucked all air from the tube to remove any foreign particles the sample could collide with and to ensure equally smooth sailing for all the ions. By keeping the charge and amount of energy applied to each particle consistent, mass became the key signature that provides researchers with every ion's chemical identity.

A computer program developed in-house generated the data in a color spectrum of masses, which was used to create topographical cell composition map.

The project was funded with $1 million from the National Institutes of Health as part of an award to the Rocky Mountain Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research. The optical equipment that focuses the laser beam was created by the Center for X-Ray Optics at the Lawrence Berkeley National Laboratory in Berkeley, Calif.

The CSU system also received support for system engineering design from Siemens, which gave the team an academic grant for its NX software package, including 30 seat licenses, valued at $37 million.

The research was published in Nature Communications (doi: 10.1038/ncomms7944) and was also described in a special issue of Optics and Photonics News.

Apr 2016
lensesmirrorsResearch & TechnologyBiophotonicsColoradoAmericasimagingopticsBioScan

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