Integrating Magnetic and Optical Nanotechnology for Selective Capture and Multiplexed Analysis of Rare Tumor Cells Tushar Sathe, Ali Saheb and Shuming Nie Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta, USA snie@emory.edu Abstract— The molecular analysis of disseminated tumor cells from blood or lymph represents an important diagnostic tool as metastasis is the primary cause of patient mortality due to cancer. Isolating tumor cells from blood is technically challenging due to the miniscule ratio of tumor cells to normal cells. Although RT-PCR and flow-based methods have been used for molecular profiling of the captured cells, it requires cell destruction and the loss of morphological information. Here, we present a combined strategy to isolate tumor cells with magnetic nanoparticles, followed by multiple biomarker analysis using targeted Quantum Dots (QD) nanoparticles. The magnetic nanoparticles and QDs will allow efficient isolation and quantitative analysis of intact captured cells. Through this technology, patient monitoring and more effective and personalized therapy will be possible. Preliminary studies have demonstrated that the molecular profile of the cells is unaltered by the isolation procedure. Results from studies involving the isolation and profiling of cancer cells from human blood are presented. I. INTRODUCTION Metastasis involves the dissemination of tumor cells from a primary tumor to different organs of the body. The most efficient way for the cells to spread is through the blood and lymph circulatory systems. As the cells disseminate, most are detected as aberrant and destroyed by the immune system, however, a small fraction can evade the regulatory mechanisms and proliferate at a distant site. By capturing and scrutinizing these cells before they metastasize, one can obtain a real-time cellular biopsy of the tumor without using invasive needle biopsy techniques. Further, it should be possible to identify the location and determine aggressiveness of the tumor and prescribe individualized therapy for best possible outcome. Therefore, there is a need to detect, isolate, profile and enumerate these cells from bodily fluids such as blood. Here, we describe the integration of magnetic iron oxide and Quantum Dot (QD) optical nanoparticles for selectively isolating and analyzing multiple biomarkers expressed inside and on the cells. QDs are semiconductor inorganic nanocrystals, which exhibit unique fluorescent properties that can be tuned by changing material composition or size. Due to their superior photoluminescent properties compared to organic dye molecules, they have garnered much interest as biological probes and optical tags [1,2]. First, they are resistant to photobleaching and can be imaged for a prolonged period (up to several hours) [3-5]. Secondly, QDs have a broad excitation bandwidth and narrow symmetric emission spectra and a single UV light source can excite multiple color QDs. This is an important property as it allows for multiplexing and multicolor tissue and cell staining and profiling [6,7]. This allows for multiple biomolecules on a cell to be tagged and imaged with multiple color QDs. By integrating the signal from these dots, it is possible to obtain a spectral signature which can provide an estimate of the amount of the tagged biomolecule. Lastly, QDs have a large extinction coefficient (in the order of 100-1000 times more than fluorescent dyes) and as a result they are very bright[1,5]. Similarly, magnetic iron oxide nanoparticles have unique nano-scale properties not found in the bulk phase. As particle diameter is reduced to less than 30-40 nm, they exhibit superparamagnetism, and are strongly magnetized only in the presence of an external magnetic field. Due to this property, these particles are seeing application in a wide range of separation processes. Although, such nanoparticles have been used in the past for cell capture, advances in nanoparticle synthetic chemistry[8] have made it possible to synthesize a large batch of highly monodisperse magnetic nanoparticles [9,10]. The magnetic properties of the uniform nanoparticles can be tuned precisely and also enable more efficient biological tagging and separation. 6 1-4244-1262-5/07/$25.00 ©2007 IEEE IEEE SENSORS 2007 Conference