Originally Published MDDI September 2005
|Parafin blocks are cut to a desired thickness and reassembled. The stacks are then sectioned into a third dimension to be placed on a slide.|
A technology that analyzes tissue samples by the thousands may not only be able to spot disease-indicating biomarkers, but also to move diagnostics into the world of automated image analysis. Researchers at Georgetown University's Lombardi Comprehensive Cancer Center (Washington, DC) say these developments could offer clearer insight into cancer and other illnesses.
Cutting Edge Matrix Assembly (CEMA) technology makes micro-arrays of tissues or other solid samples for viewing on a slide. CEMA builds arrays by repeatedly sectioning sample plates of tissue, which are then bonded. The stacks are then transversely cut and bonded edge-to-edge. The arrays are thinly sliced for analysis.
The high-throughput technology currently uses standard lab equipment and cheap reagents. However, researchers are developing semiautomated equipment to simplify building CEMA arrays. Such systems should assemble samples more efficiently.
“CEMA tissue arrays will help drive the field of automated image analysis, a field that is currently very much in its infancy,” says Hallgeir Rui, MD, PhD, associate professor in the department of oncology at Georgetown.
The team is working to improve current equipment to handle deeper array blocks that are, for example, 6–10 cm deep. Since the sectioning machines are designed to produce thin sample sections, adjustments to the blades and the angles could help. The front-end gear will include automated stacking and bonding equipment that can handle larger-scale samples and align them into more-precise stacks. On the back end, automated readers must be able to recognize and correctly identify thousands of samples.
“One way to envision CEMA arraying is to see it as a slice-and-dice approach, in contrast to the conventional coring method,” says Rui. The coring method uses a circular arrangement of less than 1000 tissue samples on each slide. CEMA provides square or rectangular spacing, which enables more samples to fit on a slide. The team so far has squeezed almost 12,000 liver and kidney tissue pieces on a 3 ¥ 1-in. glass slide.
The more samples available for analysis, the better the chances for uncovering new diagnostic markers. The researchers say CEMA could provide a more precise diagnosis of a disease and its outcome. Treatment could eventually be adapted on a patient-by-patient basis.
Tissue samples suitable for examination include those from aging studies or toxicology experiments. The method also may be able to assess the toxic effects of drugs and chemicals on healthy tissue. Currently, CEMA can produce arrays with thin-walled or multilayered tissues such as the intestines, bladder, and other vessels, which can't be displayed using other methods.
The National Institutes of Health funded the study. Details of the new technology are in the July issue of Nature Methods.
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