title: Rapid identification by surface-enhanced Raman spectroscopy of cancer cells at low concentrations flowing in a microfluidic channel.
abstract: Reliable identification and collection of cells from bodily fluids is of growing interest for monitoring patient response to therapy and for early detection of disease or its recurrence. We describe a detection platform that combines microfluidics with surface-enhanced Raman spectroscopy (SERS) for the identification of individual mammalian cells continuously flowing in a microfluidics channel. A mixture of cancerous and noncancerous prostate cells was incubated with SERS biotags (SBTs) developed and synthesized by us, then injected into a flow-focused microfluidic channel, which forces the cells into a single file. The spectrally rich SBTs are based on a silver nanoparticle dimer core labeled with a Raman-active small reporter molecule paired with an affinity biomolecule, providing a unique barcode whose presence in a composite SERS spectrum can be deconvoluted. Individual cancer cells passing through the focused laser beam were correctly identified among a proportionally larger number of other cells by their Raman signatures. We examine two deconvolution strategies: principal component analysis and classical least-squares. The deconvolution strategies are used to unmix the overall spectrum to determine the relative contributions between two SBT barcodes, where one SBT barcode indicates neuropilin-1 overexpression, while a second SBT barcode is more universal and indicates unspecific binding to a cell's membrane. Highly reliable results were obtained for all of the cell mixture ratios tested, the lowest being 1 in 100 cells.
authors.forename: Alessia
authors.initials: A
authors.lastname: Pallaoro
authors.forename: Mehran R
authors.initials: MR
authors.lastname: Hoonejani
authors.affiliation: §Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Braun
authors.forename: Carl D
authors.initials: CD
authors.lastname: Meinhart
authors.forename: Martin
authors.initials: M
authors.lastname: Moskovits
mesh_terms: D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation* / Q000379:methods*; D002470:Cell Survival; D006801:Humans; D057446:Hydrodynamics; D056656:Lab-On-A-Chip Devices; D016018:Least-Squares Analysis; D025341:Principal Component Analysis; D013059:Spectrum Analysis, Raman; D013499:Surface Properties; D013997:Time Factors
keywords: SERS; cancer diagnostics; chemometrics; microfluidics; multiplexed