MALDI MS Tissue Imaging and Profiling

Softer ionization. Thicker, wetter slices.

A poster on MassTech's web site presents work by researchers from MassTech and from NIH on an atmospheric pressure MALDI imaging mass spectrometer.

"...it is a softer ionization technique compared with vacuum MALDI and it can be used for thicker tissue slices without drying. AP-MALDI also enables the use of volatile matrices such as DHA (2,6-dihydroxyacetophenone). AP-MALDI-source coupled with ion-trap, QTOF or FT-ICR instruments provides MS/MS possibility for tissue imaging." 

 

Download Atmospheric Pressure MALDI Imaging Mass Spectrometry poster (168KB pdf)

Automated, Histology Directed Tissue Profiling

Molecular and Cellular Proteomics has published "A Novel Histology Directed Strategy for MALDI-MS Tissue Profiling that Improves Thoughput and Cellular Specificity in Human Breast Cancer,"  by Dale Cornett, et al. Considering clinical applications of imaging mass spectrometry, the authors

• note the need for cell-type specific profiling
• note the need for high sample throughput
• make a case for spotting vs. spraying
• describe the automated workflow, including their methods for co-registering histological features, matrix spotting sites, and MS data collection points
• compare cell type specific data from the histology-directed strategy vs. LCM

Cornett DS, Mobley JA, Dias EC, Andersson M, Arteaga CL, Sanders ME, Caprioli RM. A novel histology directed strategy for MALDI-MS tissue profiling that improves throughput and cellular specificity in human breast cancer. Molecular and Cellular Proteomics (2006) 10.1074/mcp.M600119-MCP200. Download full text and figures (2.1 MB pdf)

Sponsor Appreciation

Site sponsor and imaging mass spec service provider Protein Discovery has been busy. First, they have provided tissueimaging.org with artwork for their new corporate logo. Here's a handy guide to help you grok the change:

Old logo:

New logo:

So much better.

Second, they've put together a whole new web site, featuring descriptions of their imaging mass spectrometry services, their new PPS Silent™ Surfactant, and their upcoming MALDIplex™ M5 Sample Prep Station. I'm sure they wouldn't mind if you visited.

Third, CEO Chuck Witkowski describes Protein Discovery's ASMS debut as "a success on all fronts." Protein Discovery brought both imaging and non-imaging mass spec sample prep information and products to the conference. Their poster with LEAP Technologies on the new matrix sprayer for tissue imaging sample prep drew a cluster of interested imaging mass spectrometrists, and the company's information booth in the posters/exhibits area was quite overwhelmed Wednesday evening and Thursday morning following Wednesday afternoon's imaging sessions. More information is available on their web site; for a copy of the matrix sprayer poster, contact Jeremy Norris.

Fourth, on Tuesday  during the conference, a press release crossed the wire announcing  a cooperative imaging mass spec marketing agreement between Protein Discovery and Bruker. It was summarized thusly by GenomeWeb:

"Bruker Daltonics and Protein Discovery will co-market MALDI molecular imaging mass spectrometry products for protein biomarker discovery, the companies said today.

Protein Discovery holds a license from Vanderbilt University to provide imaging mass spectrometry services to customers in the research, pharmaceutical and diagnostics industries. Bruker, meantime, markets the MALDI Molecular Imager for this technique for research use only with Professor Richard Caprioli at Vanderbilt.

Protein Discovery's imaging mass spectrometry service laboratory is currently outfitted with Bruker instrumentation.

MALDI molecular imaging mass spectrometry reads cell type-specific protein and peptide mass spectra directly from sliced tissues. The imaging resolution of the technique enables differential mass spectrometry analysis of adjacent tissue types within a single tissue slice, such as cancerous versus non-cancerous regions."

Also at ASMS, it was the editor's privilege to meet many of the imaging mass spectrometrists mentioned previously on this site, including Richard Caprioli, and Swiss Alps snowboarder Markus Stoeckli, who advised us to "Keep posting interesting content. Keep it going."

Biomarker Discovery by Tissue Profiling at ASMS 2005

At ASMS 2005, Jingzhong Guo, et al., of York University (Toronto), Mount Sinai Hospital (Toronto), LEAP Technologies, and Toronto General Hospital, presented the poster "Discovery of Biomarkers for Endometrial Carcinoma by Direct Profiling of Proteins in Tissue Sections Using Selective MALDI-Spotting and MALDI MS." The presenters combined a nano-scale MALDI spotter (LEAP Technologies) with a Qstar XL MALDI-Qq-TOF mass spectrometer (Applied Biosystems) to discover up-regulated endometrial carcinoma markers.

"The challenge is to acquire protein profiles from a user-defined group of cells (e.g. cancer)."

"The protein profiles of tissue sections are similar to those from Laser Capture Microdissected tissue samples. This suggests that the selective MALDI-spotting technology is successful."

ASMS 2005 poster "Discovery of Biomarkers for Endometrial Carcinoma by Direct Profiling of Proteins in Tissue Sections Using Selective MALDI-Spotting and MALDI MS" (via LEAP Technologies' TMiD product page).

MALDI Imaging Poster at ABRF 2006

Last February's ABRF 2006 meeting featured the poster "Characterization of Human Gastric Cancer by MALDI Imaging" presented by Sören-Oliver Deininger and Martin Schürenberg of Bruker Daltonik GmbH, and Matthias Evert of Technical University of Munich, and Christoph Röcken of Berlin's Charité University Hospital.

"MALDI imaging is an emerging technology withthe potential to find biomarkers directly on tissues and measure the spatial distribution of biomarkers across the tissue (1). Here we used MALDI imaging for the analysis of human gastric cancer samples and evaluated the effect of different sample preparation methods."

"Spray preparation allows the highest spatial resolution, but dried droplet preparation (either by manual or robotic spotting) shows higher reproducibility and better spectra quality."

ABRF 2006 poster P138-T "Characterization of Human Gastric Cancer by MALDI Imaging" (via LEAP Technologies' TMiD product page).

Matrix Sprayer Development Partnership

Sensing a market, instrumentation manufacturers are getting increasingly involved in imaging mass spectrometry. In a joint press release issued this morning, Protein Discovery, Inc., provider of imaging mass spectrometry services, and LEAP Technologies announced a sample prep device development partnership.

"The partnership will focus on developing and commercializing a novel MALDI matrix sprayer for tissue imaging mass spectrometry."

Protein Discovery, Inc. Announces Development Partnership with LEAP Technologies, Inc. for Tissue Imaging Mass Spectrometry

Click on "Instrumentation" below or at left for more information on imaging mass spec instrumentation and installations.

Tissue Profiling Depth: How Low Can You Go?

About 40 microns, more or less, depending on tissue type. In their article "Investigation of the profiling depth in matrix-assisted laser desorption/ionization imaging mass spectrometry," authors Crossman, McHugh, Hsieh, Korfmacher, and Chen examined the tissue profiling depth of imaging mass spectrometry.

"MALDI matrix solution was found to be able to gain access to the tissue interior and extract analyte molecues to the tissue surface."

Crossman L, McHugh NA, Hsieh Y, Korfmacher WA and Chen J. Investigation of the profiling depth in matrix-assisted laser desportion/ionization imaging mass spectrometry. Rapid Commun Mass Spectrom. 2006; 20(2):284-90  (link goes to HubMed entry)

Technology Intro, Medical Applications

Worth the trouble of tracking it down for its list of references alone, the 2004 AJP article "Proteomics in Diagnostic Pathology: Profiling and Imaging Proteins Directly in Tissue Sections by Pierre Chaurand, et al., provides an excellent introduction to those methods, including a drive-by tour of MALDI-MS for those who might be new to the neighborhood. The authors outline potential pathology lab applications for mass spectrometry and check the capabilities of sample analysis methods against gold-standard immunohistochemistry, microscopy, and PCR-based methods for differential tumor identification, subclassification, and staging, and describe other potential uses for the demonstrated sensitivity and specificity.

Chaurand, P, Sanders, M., Jensen, R., and R. Caprioli in the American Journal of Pathology

Though this article is offered for sale, at present you can spare yourself a trip to the library, or the bank, by hitting the "FullText" link for the article on HubMed.

Matrix Application with Acoustic Drop Ejection

Matrix solutions are acidic, volatile, and nearly saturated -- a perfect storm for nozzle trouble. LabCyte, Inc. and Richard Caprioli have been investigating the adaptation of LabCyte's nozzle-free Acoustic Drop Ejection (ADE) technology to spotting matrix droplets on tissues.

  ADE for sample prep is mentioned in documents on LabCyte's web site and in US Patent 6,707,038, which lists Richard Ellson, Mitchell Mutz, and Richard Caprioli as co-inventors on "Method and System Using Acoustic Ejection for Selective Fluid Deposition on a Nonuniform Sample Surface."

Interview with Richard Ellson by Nina Bell
LabCyte poster with images shown above (900KB pdf download)
US Patent 6707038
LabCyte, Inc.
Caprioli lab at Vanderbilt

Imaging Mass Spectrometry: A new technology

"Imaging mass spectrometry: A new technology for the analysis of protein expression in mammalian tissues" from Nature Medicine presents tissue imaging technologies, methodologies, and protein expression applications as of 2001.

"Frozen sections are mounted on a metal plate, coated with an UV-absorbing matrix and placed in the mass spectrometer. A pulsed UV laser desorbs and ionizes analytes from the tissue and their m/z values are determined using a time-of-flight analyzer."

The paper is illustrated with MS images of mouse brain sections and of human glioblastoma tissues grown in mouse.

Stoeckli, Chaurand, Hallahan, and Caprioli in Nature Medicine (full text and link to pdf)
Mass Spectrometry Research Center at the Vanderbilt Medical Center