Tissue Microdissection for Molecular Analysis of Disease States and Normal Development – Target Activated Microdissection (TAM)

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:

• Increased dissection rate by orders of magnitude
• Increased dissection precision to the subcellular level
• Removed requirement for operator target selection, permitting process standardization
• Eliminated targeting difficulties due to poor image quality of histology sections
• Maintained spatial relationship of tissue morphology, allowing better image documentationStephen Hewitt, MD, PhD 

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.