title: High resolution live cell Raman imaging using subcellular organelle-targeting SERS-sensitive gold nanoparticles with highly narrow intra-nanogap.
abstract: We report a method to achieve high speed and high resolution live cell Raman images using small spherical gold nanoparticles with highly narrow intra-nanogap structures responding to NIR excitation (785 nm) and high-speed confocal Raman microscopy. The three different Raman-active molecules placed in the narrow intra-nanogap showed a strong and uniform Raman intensity in solution even under transient exposure time (10 ms) and low input power of incident laser (200 μW), which lead to obtain high-resolution single cell image within 30 s without inducing significant cell damage. The high resolution Raman image showed the distributions of gold nanoparticles for their targeted sites such as cytoplasm, mitochondria, or nucleus. The high speed Raman-based live cell imaging allowed us to monitor rapidly changing cell morphologies during cell death induced by the addition of highly toxic KCN solution to cells. These results strongly suggest that the use of SERS-active nanoparticle can greatly improve the current temporal resolution and image quality of Raman-based cell images enough to obtain the detailed cell dynamics and/or the responses of cells to potential drug molecules.
authors: Laser Biomedical Research Center, G. R. Harrison Spectroscopy Laboratory, and ‡Department of Mechanical and Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors: Jeon Woong
authors: JW
authors: Kang
authors: Peter T C
authors: PT
authors: So
authors: Ramachandra R
authors: RR
authors: Dasari
authors: Dong-Kwon
authors: DK
authors: Lim
mesh_terms: D045744:Cell Line, Tumor; D003287:Contrast Media; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008853:Microscopy / Q000379:methods*; D009062:Mouth Neoplasms / Q000473:pathology / Q000648:ultrastructure*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013347:Subcellular Fractions / Q000648:ultrastructure*
chemical_list: D003287:Contrast Media; D006046:Gold
keywords: SERS; drug-screening; intra-nanogap gold nanoparticle; live cell Raman imaging
references: Biomed Opt Express. 2011 Sep 1;2(9):2484-92
references: 21991542
references: J Am Chem Soc. 2006 Dec 13;128(49):15580-1
references: 17147354
references: Nano Lett. 2006 Apr;6(4):662-8
references: 16608261
references: Nature. 1990 Sep 20;347(6290):301-3
references: 2205805
references: J Biomed Opt. 2009 Mar-Apr;14(2):024038
references: 19405766
references: Chem Rev. 2013 Aug 14;113(8):5766-81
references: 23697873
references: Nano Lett. 2013 Jun 12;13(6):2463-70
references: 23638825
references: ACS Nano. 2014 May 27;8(5):4883-92
references: 24708404
references: J Am Chem Soc. 2014 Oct 8;136(40):14052-9
references: 25198151
references: J Phys Chem Lett. 2014 Aug 7;5(15):2555-2561
references: 25126388
references: Nano Lett. 2012 Dec 12;12(12):6170-4
references: 23151070
references: Science. 2008 Dec 19;322(5909):1857-61
references: 19095943
references: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13511-6
references: 19666578
references: J Biomed Opt. 2008 Jul-Aug;13(4):044027
references: 19021354
references: Adv Mater. 2014 Aug 13;26(30):5124-8
references: 24866811
references: J Am Chem Soc. 2011 Apr 27;133(16):6102-5
references: 21443184
references: Nano Lett. 2006 Oct;6(10):2225-31
references: 17034088
references: Nat Protoc. 2013 Apr;8(4):677-92
references: 23471112
references: Appl Opt. 2002 Oct 1;41(28):6006-17
references: 12371563
references: J Am Chem Soc. 2011 Nov 9;133(44):17594-7
references: 21981727
references: Bioconjug Chem. 2011 Nov 16;22(11):2324-31
references: 22010874
references: J Am Chem Soc. 2010 Feb 10;132(5):1517-9
references: 20085324
references: Nat Nanotechnol. 2011 Jul;6(7):452-60
references: 21623360
references: Opt Lett. 2010 Dec 15;35(24):4096-8
references: 21165101