The long-term goal of the proposed research is to develop a novel sensor device platform that is capable of detecting and molecularly profiling circulating tumor cells (CTCs) in clinical samples. CTCs are rare cancer cells that have escaped from a primary tumor site and entered the blood stream. They have been identified in the peripheral blood of most patients with metastatic disease as well as in patients with localized cancers, but at exceedingly low levels (approximately 1-100 cells per ml of blood). It is our hypothesis that these peripheral cells can be used for molecular analysis, which could non-invasively provide valuable information for use in prognosis evaluation, anticancer-drug development, and ultimately, personalized cancer therapy based on CTCs. To date, the technology required to molecularly characterize these cells is lacking because existing clinical technologies are too insensitive. In prior research, our lab developed a prototype micro- NMR (p-NMR) sensor chip that has been used to detect cancer cells that are specifically tagged with superparamagnetic nanoparticles. This technique has been termed diagnostic magnetic resonance (DMR), In this proposal 1 seek to significantly advance DMR technology so that it may be applied in clinical use for molecular detection and profiling of CTCs. To achieve this goal, DMR detection sensitivity and specificity will be dramatically increased through the following aims:
Aim 1. Extensively optimize the procedures used to tag tumor cells with magnetic nanoparticles targeted to intracellular and extracellular molecular biomarkers, and Aim 2. Develop an integrated microfluidics component that isolates CTCs from other cells in the blood based on size and delivers them directly to the p-NMR sensor. This work represents a multidisciplinary effort that calls on components from the fields of nanotechnology, molecular targeting, magnetic resonance imaging/sensing, and microfluidics to develop a novel device platform capable of interrogating clinical CTC samples, which could enable real-time molecular analysis of tumor samples and facilitate rational treatment decisions in an era where molecularly targeted therapies are emerging. The proposed research has broad applications for studying human cancer cells that are obtained from blood samples, Information could thus be obtained non-invasively to evaluate patient prognosis, devise treatment strategies, and monitor therapeutic response.
|Haun, Jered B; Devaraj, Neal K; Marinelli, Brett S et al. (2011) Probing intracellular biomarkers and mediators of cell activation using nanosensors and bioorthogonal chemistry. ACS Nano 5:3204-13|
|Haun, Jered B; Castro, Cesar M; Wang, Rui et al. (2011) Micro-NMR for rapid molecular analysis of human tumor samples. Sci Transl Med 3:71ra16|