Oak Ridge National Laboratory sees potential for clinical laboratories and pathology groups to control disease and assess treatments

What do you get by blending microscopy with mass spectrometry? A new multi-tasking tool for studying disease progression and response to treatments in patients.

Combining these two technologies into a single device could also have uses for clinical laboratory scientists and pathologists. However, much research must be done before such a device is ready to obtain FDA clearance for use in clinical settings by the nation’s medical laboratories.

The new device was created by researchers at Oak Ridge National Laboratory (ORNL) in Oak Ridge, Tenn. They created an imaging system that supplies microscopy with spatially resolved chemical analyses.

This new development will be of high interest to surgical pathologists who work with microscopes and clinical chemists who currently perform mass spectrometry testing. It shows how one research effort has the potential to bring together two technologies regularly used in laboratory medicine.

Simultaneous Microscopy and Chemical Analysis

ORNL is the largest US Department of Energy (DOE) science and energy laboratory. It conducts basic and applied research in its support of the DOE’s national missions. That includes scientific discovery.

According to a news release, ORNL’s hybrid 3D optical microscope and mass spectrometry-based imaging system makes it possible to microscopically identify and chemically analyze substances with sub-micrometer resolution concurrently.

What does this mean to the medical laboratory industry? The combination of both microscopy and mass spectrometry capabilities can improve chemical science, drug development, and even control disease, the researchers propose.

Vilmos Kertesz, PhD (left) stands with Gary Van Berkel, PhD (right), in front of an open-port sampling probe; one of several mass spectrometry technologies developed by ORNL. (Photo copyright: Oak Ridge National Laboratory.)

Vilmos Kertesz, PhD (left) stands with Gary Van Berkel, PhD (right), in front of an open-port sampling probe; one of several mass spectrometry technologies developed by ORNL. (Photo copyright: Oak Ridge National Laboratory.)

“The new tool can be used to better understand the chemical basis of important biological processes, such as drug transport, disease progression, and response to treatment,” stated Gary Van Berkel, PhD, Distinguished Research Scientist and Group Leader of ORNL’s Chemical Sciences Division, in the news release. “Knowing the chemical basis of material interactions that take place at interfaces is vital for designing and advancing new functional materials that are important for DOE missions, such as photovoltaics for solar energy,” he continued.

Room for Improvement in Mass Spectrometry Imaging

The researchers published their study in the journal Analytical Chemistry. Limitations in current mass spectrometry imaging techniques motivated the team.

“Today’s mass spectrometry imaging techniques are not up to the task of reliably acquiring molecular information on a wide range of compound types,” stated John Cahill, post-doctorate associate, and member of the ORNL research team.

A hybrid 3D optical microscope/mass spectrometry map (above) showing optical brightness [height] and chemical distribution of Poly(2-Vinylpyridine) [red] and Poly(N-Vinylcarbazole) [blue] signals of a 20-micron by 20-micron area of a polymer blend. (Image and caption copyright: ORNL/DOE.)

A hybrid 3D optical microscope/mass spectrometry map (above) showing optical brightness [height] and chemical distribution of Poly(2-Vinylpyridine) [red] and Poly(N-Vinylcarbazole) [blue] signals of a 20-micron by 20-micron area of a polymer blend. (Image and caption copyright: ORNL/DOE.)

The recently unveiled technology provides detailed chemical analysis through an interface between a hybrid optical microscope and a laser ablation electrospray ionization (LAESI) system for mass spectrometry.

“With this system, material laser-ablated from a sample using the microscope was caught by a liquid vortex capture probe and transported ‘in solution’ for analysis by electrospray ionization mass spectrometry,” the researchers wrote in the Analytical Chemistry article.

System Differs from Other Specialized Microscopes

According to Gizmag, ORNL’s system is different from other specialized microscopes for these reasons:

• No sub-zero temperature for operation required;

• No need for pre-treatment of fed samples; and

• Imaging capabilities to sub-micrometer resolution exist.

Here’s how it works, according to the Gizmag article:

• Materials are provided for mass spectrometry using an ultraviolet laser ablation process;

• The process removes tiny amounts of material for analysis from the sample;

• Material is fed into a pumped stream of inert liquid;

• The liquid is ionized in the mass spectrometer;

• Results are displayed in seconds on a computer monitor attached to the machine.

Tweeny Weeny Results

The system enabled the researchers to identify trace amounts of cocaine within thin tissue sections of a mouse brain. In fact, they distinguished features as small as 15 micrometers in both mass spectral and optical images, according to an article in Microscopy and Analysis. Incidentally, one micrometer equals about 1/100th the width of a human hair. That’s really small!

Prior Research Produces Chemical Sampling Interface

Earlier research by Van Berkel and Vilmos Kertesz, PhD, of the ORNL Researcher Mass Spectrometry and Laser Spectrometry Group, focused on the open port sampling interface for identifying and characterizing solid or liquid samples.

“The simplicity of our device allows even novices with the means to introduce unprocessed solid or liquid samples into a mass spectrometer without fear of instrument contamination,” Van Berkel stated in an ORNL news release.

ORNL researchers believe the technology has been on the wish list of research laboratories for some time. They reportedly see the cheap, fast, and multi-tasking system for mass spectrometry to be a breakthrough for these labs. If the technology proves accurate and robust in research settings, then clinical laboratories will be interested in using such systems in support of patient care.

—Donna Marie Pocius

Related Information:

New ORNL Device Combines Power of Mass Spectrometry, Microscopy

Characterization and Application of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging with Submicrometer Spatial Resolution

ORNL’s Hybrid Device Combines Microscopy and Mass Spectrometry

System Detect Cocaine in Mouse Brain and More

ORNL Chemical Sampling Interface Features Simplicity, Speed

An Open Port Sampling Interface for Liquid Introduction Atmospheric Pressure Ionization Mass Spectrometry