Rapid detection and profiling of cancer cells in fine-needle aspirates.
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.
Lee
Hakho
H
Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA 02114, USA.
Yoon
Tae-Jong
TJ
Figueiredo
Jose-Luiz
JL
Swirski
Filip K
FK
Weissleder
Ralph
R
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
D018719:Erb-b2 Receptor Tyrosine Kinases