title: Rapid detection and profiling of cancer cells in fine-needle aspirates.
abstract: There is a growing need for fast, highly sensitive and quantitative technologies to detect and profile unaltered cells in biological samples. Technologies in current clinical use are often time consuming, expensive, or require considerable sample sizes. Here, we report a diagnostic magnetic resonance (DMR) sensor that combines a miniaturized NMR probe with targeted magnetic nanoparticles for detection and molecular profiling of cancer cells. The sensor measures the transverse relaxation rate of water molecules in biological samples in which target cells of interest are labeled with magnetic nanoparticles. We achieved remarkable sensitivity improvements over our prior DMR prototypes by synthesizing new nanoparticles with higher transverse relaxivity and by optimizing assay protocols. We detected as few as 2 cancer cells in 1-microL sample volumes of unprocessed fine-needle aspirates of tumors and profiled the expression of several cellular markers in <15 min.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.forename: Tae-Jong
authors.initials: TJ
authors.lastname: Yoon
authors.forename: Jose-Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D000818:Animals; D044963:Biopsy, Fine-Needle; D015374:Biosensing Techniques; D015153:Blotting, Western; D002452:Cell Count; D045744:Cell Line, Tumor; D003581:Cytodiagnosis / Q000295:instrumentation / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods*; D008280:Magnetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D046210:Microfluidic Analytical Techniques; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases