| Despite significant developments in imaging modalities and therapeutics, cancer mortality rates remain unchanged. Detecting cancer before it has spread to other organs improves patient outcome dramatically. Therefore, greater emphasis must be placed on developing novel technology for early cancer detection and disease monitoring. Nanometer-sized materials have unique optoelectronic and magnetic properties that are not available from their bulk phase. Since they are in the same mesoscopic size regime as biological molecules, they can be used to target and quantify individual molecules in a cell or in solution. In particular, semiconductor quantum dots (QD) are a new class of fluorophores that are bright, photostable, and can be simultaneously excited to emit different wavelengths of light. Magnetic iron oxide nanoparticles are another class of unique nanomaterials that exhibit superparamagnetism and are strongly magnetized only in the presence of a magnetic field. In this dissertation, we describe the integration of semiconductor QDs and magnetic iron oxide nanoparticles and potential applications for (i) early detection of cancer biomarkers through routine screening, and (ii) disease monitoring through the capture and analysis of rare circulating tumor cells. First, we describe the development of integrated magneto-optical beads that can be optically encoded and magnetically separable for isolating low amounts of biomolecules from solution. Second, we demonstrate improved detection sensitivity by combining immunomagnetic beads and highly luminescent nanoparticles in a sandwich assay. Next, we describe integration of magnetic and QD nanotechnology for the selective capture and molecular profiling of rare cells. We demonstrate the ability to spectroscopically determine relative molecular levels of markers to identify invasive cells. As disease monitoring requires the analysis of patient blood samples, we have also studied nanoparticle-cell interactions using QDs to determine nanoparticle behavior in whole blood as a function of surface coatings. We observed that anionic nanoparticles with carboxylic acid groups (-COOH) were strongly associated with leukocytes, but interestingly this association was cell specific. Hydroxyl-modified QDs (QD-OH) suppressed binding and uptake by leukocytes as efficiently as PEG-modified QDs. The integration of nanotechnologies represents a new and exciting approach that has the potential to push the limits of detection sensitivity and permit isolation and profiling of multiple biomarkers from large sample volumes. |
