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LEAP, Protein Discovery to Release First Robotic MALDI Matrix Sprayer for Tissue Imaging in May


LEAP Technologies, in partnership with Protein Discovery, is planning on releasing a robotic MALDI matrix sprayer at the end of next month. The companies claim the tool will facilitate tissue imaging using MALDI mass spectrometry.

Researchers in Richard Caprioli's laboratory at Vanderbilt University pioneered the development of MALDI imaging technology in the late 1990's as an alternative to traditional immunohistochemistry. With imaging mass spectrometry, pieces of frozen tissue are sprayed or spotted with MALDI matrix, then scanned with a MALDI instrument equipped with a laser that ionizes the sample. The ionized sample enters into the mass spectrometer, and a "snapshot" image of what proteins, peptides, or small molecules are present in the tissue can be produced based on mass spectra.

The advantage of using a robotic MALDI matrix sprayer is that the spray pattern and spray thickness can be very consistent, said Scott Johnson, a proteomic sales specialist at LEAP Technologies. That could lead to more reproducible tissue images.

"A sprayer is like an airbrush," said Johnson. "It's hard to do it manually and get it exactly right. It's kind of an art form if you do it manually. With an automated system, you can get a very consistent spray pattern."

"A sprayer is like an airbrush: It's hard to do it manually and get it exactly right. It's kind of an art form if you do it manually. With an automated system, you can get a very consistent spray pattern."

Michelle Reyzer, a research instructor in the Caprioli research group at Vanderbilt who uses tissue imaging to study breast cancer, colon cancer, and melanoma, among other things, agreed with Johnson that it is hard to control for certain conditions like spray distance, volume, and speed, when spraying manually.

"To be able to have all the conditions reproducible would be useful," said Reyzer.

To Johnson's knowledge, the LEAP sprayer will be the first commercially available robotic MALDI matrix sprayer.

The patented nozzle for the robotic sprayer was first developed by the Massachusetts Institute of Technology, which licensed the technology to Lab Connections. This company, focused on automated sample preparation, used the technology for a non-MALDI application.

LEAP acquired Lab Connections last month, and last week the company formalized a partnership with Protein Discovery to develop the nozzle technology into a robotic MALDI matrix sprayer.

Protein Discovery, based in Knoxville, Tenn., provides a tissue imaging mass spectrometry service to pharmaceutical and clinical research customers. The company will be developing and testing the new MALDI matrix sprayer. Once the product is fully developed, LEAP will market and distribute it, Johnson said.

"They're doing the science, and we're going to do the distribution," he said.

The new sprayer will probably be released at the American Society of Mass Spectrometry conference scheduled to take place May 28 through June 1 in Seattle, said Johnson.

Aside from the new MALDI matrix sprayer, LEAP has another product designed to robotically spot MALDI matrix onto tissue samples. The product, called TMiD, was released at last year's ASMS conference, and competes with Shimadzu's and Labcyte's robotic spotters. It costs $75,000 to $80,000, according to Johnson.

"The thing that's different about TMiD and those other two spotters [by Shimadzu and Labcyte] is that we have a camera on ours that allows you to take an image of the tissue and to select where you want to place the spots," said Johnson.

Reyzer said she is not familiar with LEAP's TMiD robotic spotter. Her lab uses robotic spotters from LEAP's competitors: one spotter from Shimadzu, and another from Labcyte.

"The key is to have very small drops, very high placement accuracy, and also to contact the tissue for long enough," said Reyzer. "Our two spotters deposit picoliter volume droplets, but you need to do multiple passes on the spots. With multiple repetitions, we usually get spots on the order of 200 microns in diameter... The smaller the spot, the smaller region you can image at a high resolution."

LEAP's TMiD instrument deposits spots that are about 200 to 500 microns in diameter, said Johnson.

Though researchers in Caprioli's lab have been doing MALDI imaging for over five years, the technology is still very much of an up-and-coming area, said Johnson.

"I'm surprised more people don't know about it," he said. "We're still in the educational phase."

A main advantage of imaging mass spec over other, more traditional proteomics techniques is that it allows scientists to visualize where things are localized, said Reyzer.

"With roughly one experiment, you can get localizations of literally hundreds of thousands of proteins," she said. "It's very much a hypothesis-generating type of experiment, rather than a hypothesis-driven experiment. You're saying, for example, 'What are the different biochemistries of proteins in these certain areas?' rather than, 'I think the protein is going to be expressed here.' It generates a lot of new avenues for research."

In addition, the technique requires very little sample, and very little sample preparation, Reyzer added.

Advantages of imaging mass spec over immunohistochemistry staining include the ability to obtain images without antibodies, the ability to generate thousands of protein/peptide mass spectra-based images from one experiment, and the ability to generate a picture without knowing what protein or peptide to look for.

"We often validate imaging mass spec by using an immunohistochemistry stain," said Reyzer. "It's very much a complementary technique. You can use it in conjunction with all the other techniques out there."

— Tien-Shun Lee ([email protected])

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