2337 lines
86 KiB
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2337 lines
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<meta name="description" content="An IDEAS project that improves target activated microdissection (TAM) to enhance molecular analysis of tissue." />
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<title>Tissue Microdissection for Molecular Analysis of Disease States and Normal Development – Target Activated Microdissection (TAM) | National Institute of Biomedical Imaging and Bioengineering</title>
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<article data-history-node-id="136396" about="/labs-at-nibib/ideas-lab/projects/tissue-microdissection-molecular-analysis-disease-states-normal-development-target-activated-microdissection-tam" class="ideas-projects node--ideas-projects node--type-ideas-projects">
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<h2 class="field--label">Collaborators</h2>
|
||
</div>
|
||
<div class="field--items grid-row flex-row">
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
||
|
||
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||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Stephen Hewitt, M.D., Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Laboratory of Pathology, Experimental Pathology Laboratory, NCI</div>
|
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||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
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<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Jeff Hanson</span></div>
|
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|
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|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Laboratory of Pathology, Experimental Pathology Laboratory, NCI</div>
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||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
||
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||
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||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Henry Eden, M.D., Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Biomedical Engineering & Physical Science Shared Resource Program, NIBIB</div>
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||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
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||
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||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Nicole Morgan, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Biomedical Engineering & Physical Science Shared Resource Program, NIBIB</div>
|
||
|
||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
||
|
||
|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Robert Bonner, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Section on Medical Biophysics, Program in Physical Biology, NICHD</div>
|
||
|
||
</div>
|
||
</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
||
|
||
|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Brandon Harvey, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Molecular Mechanisms of Cellular Stress and Inflammation, Integrative Neuroscience Research Branch, NIDA</div>
|
||
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|
||
</span>
|
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<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
|
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|
||
<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Benes Trus, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Mathematical & Statistical Computing Laboratory, Office of Intramural Research, CIT</div>
|
||
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|
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</span>
|
||
<span class="grid-col flex-auto"> <div class="paragraph paragraph--type--collaborators paragraph--view-mode--default">
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||
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<div class="field field--name-field-collaborator field--type-link field--label-hidden field__item"><span>Philip McQueen, Ph.D.</span></div>
|
||
|
||
|
||
<div class="field field--name-field-institution field--type-string field--label-hidden field__item">Mathematical & Statistical Computing Laboratory, Office of Intramural Research, CIT</div>
|
||
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|
||
<div class="ideas-project-section-title">
|
||
<h2>Project Brief</h2>
|
||
</div>
|
||
|
||
|
||
<div class="field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Laser Capture Microdissection (LCM) is a well-established technology used to isolate cells of interest from surrounding tissue cells on a microscope slide. As early co-inventors of LCM in the mid-90s, SPIS staff have continued to develop innovative tissue microdissection technologies, working with partners in NCI, NICHD, NIBIB, NIMH, NIDA, and industry. Although LCM is already commercially successful, the method requires a skilled operator to select the cells for capture, which leads to operator variability and limits overall throughput. In more recent years, SPIS and collaborators have developed Target Activated Microdissection (TAM) to address these limitations associated with some applications. TAM uses targeted molecular probes and light-absorbing tissue stains that generate localized heat under suitable illumination, bonding the desired cells to a thin thermoplastic placed in contact with the tissue. The initial TAM prototype used a scanned laser to illuminate the entire tissue section, in which the following performance enhancements were achieved:</p>
|
||
<ul>
|
||
<li>Increased dissection rate by orders of magnitude</li>
|
||
<li>Increased dissection precision to the subcellular level</li>
|
||
<li>Removed requirement for operator target selection, permitting process standardization</li>
|
||
<li>Eliminated targeting difficulties due to poor image quality of histology sections</li>
|
||
<li>Maintained spatial relationship of tissue morphology, allowing better image documentationStephen Hewitt, MD, PhD </li>
|
||
</ul>
|
||
<p>To further improve TAM performance, SPIS designed and produced a custom light source that delivers a brief, high-power, burst of light over the entire surface area of the tissue, reducing the time required to dissect tissue from a whole slide with subcellular precision to under a minute. During validation studies, SPIS introduced a variety of TAM instrumentation features, such as the ability to use multiple pulses in quick succession, the ability to alter the spectrum of light with filters, and the ability to save and reload settings for repeatable experiments. TAM developments have resulted in patents, licensing, and MTAs.</p>
|
||
|
||
<figure role="group" class="align-center">
|
||
<img alt="Overview of TAM Process" data-entity-type="file" data-entity-uuid="5a077d80-aafb-45f2-8fcf-53607b79fcb0" src="/sites/default/files/inline-images/TissueMicroDissection1.png" width="429" height="608" loading="lazy">
|
||
<figcaption>As an evolution of Laser Capture Microdissection, the Target Activated Microdissection (TAM) process facilitates microdissection use in clinical genomics, epigenomics, gene expression diagnostics, proteomics, and functional biomarker applications. The TAM process (I) begins with an immunolabeled or stained tissue section. A thin thermoplastic film is placed in direct contact with the tissue with the aid of a vacuum, and light is applied over the entire tissue section (II). The labeled tissue targets absorb the light and increase in temperature, causing adhesion to the film, which is then removed along with the labeled tissue targets (III).</figcaption>
|
||
</figure>
|
||
<p> </p>
|
||
|
||
<figure role="group" class="align-center">
|
||
<img alt="fTAM instrumentation 3D model and prototype" data-entity-type="file" data-entity-uuid="99e18689-819e-4e19-aa95-88220ece597a" src="/sites/default/files/inline-images/TissueMicroDissection2.png" width="741" height="565" loading="lazy">
|
||
<figcaption>Development of flashlamp Target Activated Microdissection (fTAM). The earliest prototypes of TAM technology leveraged existing Laser Capture Microdissection (LCM) instrumentation based on laser systems. While effective, these LCM systems did not fully realize the benefits of TAM due to their limited light spectrum (single wavelength lasers) and limited speeds (small diameter laser beams were raster scanned over the entire tissue sample). SPIS engineers designed and built a novel TAM light source based on a high-power flashlamp. This development utilized a wide range of SPIS capabilities including analog circuit design (for bulb charging, bulb flashing, and safety locks), microcontroller programming (for user interface, logging, and configuration), optics design (for filters, bulb placement, reflectors), 3D modeling (I and II), and a variety of fabrication techniques, including in-house printed circuit boards, laser cutting, 3D printed parts, and mechanical assembly (III and IV).</figcaption>
|
||
</figure>
|
||
<p> </p>
|
||
<div>
|
||
|
||
|
||
|
||
<div class="blazy blazy--nojs blazy--field blazy--field-media-oembed-video blazy--field-media-oembed-video--default field field--name-field-media-oembed-video field--type-string field--label-hidden field__item" data-blazy> <div data-b-token="b-caa6bf561f6" class="media media--blazy media--youtube media--bundle--remote-video media--video media--ratio media--ratio--169"> <iframe allowfullscreen src="/media/oembed?url=https%3A//youtu.be/IxBug82LkKI&max_width=0&max_height=0&hash=nJKNH1_OQvAr1re0lr6riIZYrAvKzcbooNluhUaS-T0&blazy=1" class="media__element" loading="lazy"></iframe>
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||
</div>
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||
</div>
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||
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||
</div>
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||
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<div class="field field--name-field-nibib-site-page-cards field--type-entity-reference-revisions field--label-hidden field__items">
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||
<div class="horz-card-item">
|
||
<a href="/labs-at-nibib/ideas-lab/publications" class="horz-card-text-link">
|
||
<h3 tab index="0" class="horz-heading--half-width horz-para-title">
|
||
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||
<div class="field field--name-field-card-title field--type-string field--label-hidden field__item">Publications</div>
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</h3>
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</a>
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</div>
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<!-- new and improved varient of accent border color -->
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<div class="height-3px width-full default-border-accent">
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||
</div>
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||
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||
|
||
<div class="field field--name-field-card-text field--type-text-long field--label-hidden field__item"><p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767164/">Proteomic analysis of nuclei dissected from fixed rat brain tissue using expression microdissection</a></p>
|
||
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794997/">Immunoguided Microdissection Techniques</a></p>
|
||
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795005/">Expression microdissection adapted to commercial laser dissection instruments</a></p>
|
||
<p>Expression Microdissection: A Novel Immuno-Based Dissection Technology for Cellular and Nuclear Procurement <em>(unavailable)</em></p>
|
||
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1420331/">Tumor-associated endothelial cells display GSTP1 and RARβ2 promoter methylation in human prostate cancer</a></p>
|
||
<p><a href="https://pubmed.ncbi.nlm.nih.gov/15538110/">Expression microdissection: operator-independent retrieval of cells for molecular profiling</a></p>
|
||
<p><a href="https://pubmed.ncbi.nlm.nih.gov/10023545/">Laser Capture Mircrodissection of Single Cells From Complex Tissues</a></p>
|
||
<p>An Instrument for Performing Laser Capture Microdissection of Single Cells <em>(unavailable)</em></p>
|
||
<p><a href="https://pubmed.ncbi.nlm.nih.gov/9411767/">Laser Capture Microdissection: Molecular Analysis of Tissue</a></p>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
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||
</div>
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<h3 tab index="0" class="horz-heading--half-width horz-para-title">
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<div class="field field--name-field-card-title field--type-string field--label-hidden field__item">Tech Transfer</div>
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</h3>
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</div>
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</div>
|
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<!-- new and improved varient of accent border color -->
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<div class="height-3px width-full default-border-accent">
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</div>
|
||
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||
|
||
<div class="field field--name-field-card-text field--type-text-long field--label-hidden field__item"><p>Patent licensing: XMD Diagnostics, LLC</p>
|
||
<p>MTAs with industry partners for internal use and commercialization</p>
|
||
<p>CRADA negotiations with industry partner for pre-licensing evaluation</p>
|
||
<p>Technology Dissemination: Expression Microdissection highlighted as a <a href="https://irp.nih.gov/catalyst/v19i6/new-methods">‘New Methods’ article</a> in the ‘NIH Catalyst’, a publication about NIH intramural research</p>
|
||
<p>International patent application: Device for Selectively Removing Cells from a Biological Sample</p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US8460744">Target activated microtransfer</a></p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US7709047">Method patent: Target activated microtransfer</a></p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US7695752">Device patent: Target activated microtransfer</a></p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US6897038">Method of laser capture microdissection from a sample utilizing short pulse length</a></p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US6743601">Non-contact Laser Capture Microdissection</a></p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US6783734">Convex geometry adhesive film system for laser capture microdissection</a></p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US6720191">Mechanical Handling Systems for Laser Capture Microdissection</a></p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US6420132">Precision laser capture microdissection utilizing short pulse length</a> </p>
|
||
<p>Patent: <a href="https://patents.google.com/patent/US6100051">Method utilizing convex geometry for laser capture microdissection</a> </p>
|
||
</div>
|
||
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