Potential Contribution in Biomedical Engineering

Microarray Analysis for Early Detection

The advent of microfluidic technology and microarray technology can potentially revolutionize the point of care diagnostics.  By applying these diagnostic tools for the early and rapid detection of thyroid cancer can potentially improve the prognosis of the disease.  As with all cancers, malignancies within the thyroid are caused by aberrant expressions of genes involved in cellular proliferation, contact inhibition, and metabolism of extracellular matrix.  Specifically, in thyroid cancer the MAPK pathway have been shown to be linked to the tumorigenesis process.  Molecules within this pathway such as RET and BRAF, are upregulated in ~80% of patients diagnosed with thyroid cancer and who’ve been exposed to high levels of radiation [3, 10].  High incidences of this phenomenon have been linked to the Chernobyl nuclear disaster in Eastern Europe [3].  These characteristic genetic mutations can potentially be used for the rapid detection of thyroid cancer.  By linking the synthesizing fluorescently labeled antibodies with epitopes specific for the proteins of interest, it may potentially be used for the detection of cancer cells.  Although rare, distant metastasis of thyroid cancer may be screened by isolation of the rare cell population which are circulating within the blood stream.  Thus by targeting these genetic marker, the early detection of cancer may be possible. Methods involving fluorescent enhancement can further be used to amplify the signal of the fluorophore.  In a report by Fu et. al. it was shown that fluorescent signal can be enhanced through the use of surface plasmon effects [19].

Figure 6: Microfeatures for fluorescent enhancement. SEM images of biaxial a) and uniaxial b) wrinkles. c) Fluorescent signal on glass substrate as compared to gold features. Fluorescent lifetime measurements d) of gold versus glass substrate shows enhancement on microstructures [19].

Figure 7: Nanofeatures and fluorescent enhancement.  Through heat-induced shrinkage a) of gold plated polyolefin, nanofeatures are created b).  Using microcontact printing, fluorescent signals from microarrays printing are enhanced through protein concentration  [20].

In a recent publication by Nguyen et. al. it was shown that the fluorescent signal of primary polycolonal antibodies can be concentration upon microarray polymer to detect low concentrations of fluorescent signal [20].  Theoretically, this method can be used in whole cell lysates to amplify the signal of protein concentrations.  This method can then be applied to the detection of aberrant protein expression in malignant cells such as those of the MAPK pathway.  Thus by combining the technology of microfluidics with protein arrays, it is possible to amplify biological signals, making the detection of rare cell populations and their corresponding protein expression a possibility of the near future.