How to cite this WIREs title:
WIREs Nanomed Nanobiotechnol

Impact Factor: 7.689

Using nanoparticles to push the limits of detection

Advanced Review

Nathan J. Wittenberg, Christy L. Haynes

Published Online: Feb 17 2009

DOI: 10.1002/wnan.19

Full article on Wiley Online Library: HTML PDF

Can't access this content? Tell your librarian.

Abstract The size‐dependent chemical and physical properties of nanoparticles inspire the design of unique assays and the use of new detection schemes while also offering the opportunity to vastly improve the results achieved when using traditional signal transduction methods. Herein, the most commonly exploited nanoparticle amplification schemes are organized and reviewed on the basis of the detection methods used to monitor the nanoparticle property of interest. The topics covered include the improved signal photostability and brightness of semiconductor quantum dots, the increased extinction coefficient of noble metal nanoparticles, the advantages of having a magnetic label on individual target molecules to facilitate separation, the multiplexing that is enabled with ‘barcoded’ nanoparticles, and the greatly amplified signals that can be achieved on the basis of conductivity changes, generated current, or simply by adding a ‘massive’ nanoparticle onto a small molecule target. Common approaches emerge among different nanoparticle materials and detection schemes, and it is also clear that there is still significant opportunity to use nanoparticles in as‐yet‐unimagined ways to further improve assay and sensor limits of detection Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale

This WIREs title offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images

Figure showing the localization of PEG‐g‐PEI coated QDs with (a) longer and (b) shorter PEG chain lengths. (Reprinted, with permission, from Ref. 5. Copyright 2007 American Chemical Society.).

[ Normal View | Magnified View ]

(a) Schematic representation of the sandwich hybridization that occurs between two sets of probe DNA and target DNA, resulting in the aggregation of the nanoparticles. (b) AFM images of nanoparticle aggregates induced by the addition of target DNA at various concentrations; a: 10 nM (91.3 ± 6.6 nm), b: 1 nM (86.8 ± 3.9 nm), c: 100 pM (80.6 ± 3.1 nm), and d: 10 pM (75.0 ± 4.3 nm). The particle size increases with the concentration of target DNA. Scale bar: 1µm. (Reprinted, with permission, from Ref. 66. Copyright 2006 Springer.).

[ Normal View | Magnified View ]

(a) Schematic representation of SECM imaging of DNA hybridization on a microarray. The attachment of the streptavidin–gold nanoparticles and the silver precipitation at a spot where hybridization has occurred results in an SECM positive feedback. The gray circles represent biotin molecules, whereas the ovals and the empty circles are the streptavidin molecules and the gold nanoparticles, respectively. The silver particles deposited onto the streptavidin–gold nanoparticle conjugates are shown by the filled circles. (b) A SECM image of six spots of the same probe on a microarray surface. (Reprinted, with permission, from Ref. 53. Copyright 2001 American Chemical Society.).

[ Normal View | Magnified View ]

Scheme depicting the analytical procedure for using the Pt‐NPs in the analysis of (a) DNA and (b) thrombin. (Reprinted, with permission, from Ref. 51. Copyright 2005 American Chemical Society.).

[ Normal View | Magnified View ]

Multitarget electrical DNA detection protocol based on different inorganic colloid nanocrystal tracers. (a) Introduction of probe‐modified magnetic beads. (b) Hybridization with the DNA targets. (c) Second hybridization with the QD‐labeled probes. (d) Dissolution of QDs and electrochemical detection. (Reprinted, with permission, from Ref. 44. Copyright 2003 American Chemical Society.).

[ Normal View | Magnified View ]

Scheme showing concept behind electrical detection of DNA. (Reprinted, with permission, from Ref. 29. Copyright 2006 AAAS.).

[ Normal View | Magnified View ]

Reflectance (a) and fluorescence (b) images of striped nanobarcodes with five different patterns. On the basis of selective labeling, only three nanobarcode populations are visible in the fluorescence image. (Reprinted, with permission, from Ref. 19. Copyright 2003 Springer.).

[ Normal View | Magnified View ]

Fe₃O₄ nanoparticle size effects on magnetic behavior. (a) TEM images of nanoparticles, (b) and (c) size‐dependent T₂ characteristics, (d) T₂ values as a function of size, and (e) magnetization as a function of size. (Reprinted, with permission, from Ref. 14. Copyright 2005 American Chemical Society.).

[ Normal View | Magnified View ]

Scheme showing the stepwise extraction of different cell populations using magnetic nanoparticles. (Reprinted, with permission, from Ref. 12. Copyright 2007 American Chemical Society.).

[ Normal View | Magnified View ]

References

Henglein, A. Photochemistry of colloidal cadmium sulfide. 2. Effects of adsorbed methyl viologen and of colloidal platinum J Phys Chem 1982, 86(13): 2291–2293.
Rossetti, R, Nakahara, S, Brus, LE. Quantum size effects in the redox potentials, resonance Raman spectra, and electronic spectra of cadmium sulfide crystallites in aqueous solution J Chem Phys 1983, 79(2): 1086–1088.
Klostranec, JM, Chan, WCW. Quantum dots in biological and biomedical research: recent progress and present challenges Adv Mater 2006, 18(15): 1953–1964.
Michalet, X, Pinaud, FF, Bentolila, LA, Tsay, JM, Doose, S, et al. Quantum dots for live cells, in vivo imaging, and diagnostics Science 2005, 307(5709): 538–544.
Duan, H, Nie, S. Cell‐penetrating quantum dots based on multivalent and endosome‐disrupting surface coatings J Am Chem Soc 2007, 129(11): 3333–3338.
Fu, A, Gu, W, Boussert, B, Koski, K, Gerion, D, et al. Semiconductor quantum rods as single molecule fluorescent biological labels Nano Lett 2007, 7(1): 179–182.
Peng, J, Wang, K, Tan, W, He, X, He, C, et al. Identification of live liver cancer cells in a mixed cell system using galactose‐conjugated fluorescent nanoparticles Talanta 2007, 71(2): 833–840.
Wang, L, Yang, C, Tan, W. Dual‐luminophore‐doped silica nanoparticles for multiplexed signaling Nano Lett 2005, 5(1): 37–43.
Huhtinen, P, Vaarno, J, Soukka, T, Lovgren, T, Harma, H. Europium(III) nanoparticle‐label‐based assay for the detection of nucleic acids Nanotechnology 2004, 15(12): 1708–1715.
Valanne, A, Huopalahti, S, Vainionpaeae, R, Loevgren, T, Haermae, H. Rapid and sensitive HBsAg immunoassay based on fluorescent nanoparticle labels and time‐resolved detection J Virol Methods 2005, 129(1): 83–90.
Sathe, TR, Agrawal, A, Nie, S. Mesoporous silica beads embedded with semiconductor quantum dots and iron oxide nanocrystals: dual‐function microcarriers for optical encoding and magnetic separation Anal Chem 2006, 78(16): 5627–5632.
Smith, JE, Medley, CD, Tang, Z, Shangguan, D, Lofton, C, et al. Aptamer‐conjugated nanoparticles for the collection and detection of multiple cancer cells Anal Chem 2007, 79(8): 3075–3082.
Muller, RN, Roch, A, Colet, J‐M, Ouakssim, A, Gillis, P. Particulate magnetic contrast agents In: Merbach, AE, Toth, E., eds. The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging. New York: John Wiley %26 Sons; 2001, 417–435.
Jun, Y‐W, Huh, Y‐M, Choi, J‐S, Lee, J‐H, Song, H‐T, et al. Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging J Am Chem Soc 2005, 127(16): 5732–5733.
Brahler, M, Georgieva, R, Buske, N, Muller, A, Muller, S, et al. Magnetite‐loaded carrier erythrocytes as contrast agents for magnetic resonance imaging Nano Lett 2006, 6(11): 2505–2509.
Perez‐Luna, VH, Aslan, K, Betala, P. Colloidal gold In: Nalwa, HS. Encyclopedia of Nanoscience and Nanotechnology. New York: American Scientific Publishers; 2004, 27–49.
Haynes, CL, Haes, AJ, McFarland, AD, Van Duyne, RP. Nanoparticles with tunable localized surface plasmon resonances: Topics in fluorescence spectroscopy. Topics in Fluorescence Spectroscopy. Radiative Decay Engineering, New York: Springer; 2005, 8: 47–99.
Haes, AJ, Van Duyne, RP. A nanoscale optical blosensor: sensitivity and selectivity of an approach based on the localized surface plasmon resonance spectroscopy of triangular silver nanoparticles J Am Chem Soc 2002, 124(35): 10596–10604.
Keating, CD, Natan, MJ. Striped metal nanowires as building blocks and optical tags Adv Mater 2003, 15(5): 451–454.
Walton, ID, Norton, SM, Balasingham, A, He, L, Oviso, DF Jr, et al. Particles for multiplexed analysis in solution: detection and identification of striped metallic particles using optical microscopy Anal Chem 2002, 74(10): 2240–2247.
Huang, X, El‐Sayed, IH, Qian, W, El‐Sayed, MA. Cancer cell imaging and photothermal therapy in the near‐infrared region by using gold nanorods J Am Chem Soc 2006, 128(6): 2115–2120.
Mirkin, CA, Letsinger, RL, Mucic, RC, Storhoff, JJ. A DNA‐based method for rationally assembling nanoparticles into macroscopic materials Nature 1996, 382(6592): 607–609.
Elghanian, R, Storhoff, JJ, Mucic, RC, Letsinger, RL, Mirkin, CA. Selective colorimetric detection of polynucleotides based on the distance‐dependent optical properties of gold nanoparticles Science 1997, 277(5329): 1078–1080.
Nam, J‐M Park, S‐J, Mirkin, CA. Bio‐barcodes based on oligonucleotide‐modified nanoparticles J Am Chem Soc 2002, 124(15): 3820–3821.
Schatz, GC, Young, MA, Van Duyne, RP. Electromagnetic mechanism of SERS. Topics in Applied Physics. Surface‐enhanced Raman Scattering, Vol. 103; New York: Springer; 2006, 19–46.
Mulvaney, SP, Musick, MD, Keating, CD, Natan, MJ. Glass‐coated, analyte‐tagged nanoparticles: a new tagging system based on detection with surface‐enhanced raman scattering Langmuir 2003, 19(11): 4784–4790.
Cao, YC, Jin, R, Mirkin, CA. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection Science 2002, 297(5586): 1536–1540.
Stuart, DA, Yuen, JM, Shah, N, Lyandres, O, Yonzon, CR, et al. In vivo glucose measurement by surface‐enhanced raman spectroscopy Anal Chem 2006, 78(20): 7211–7215.
Park, SJ, Taton, TA, Mirkin, CA. Array‐based electrical detection of DNA with nanoparticle probes Science 2002, 295(5559): 1503–1506.
Li, J, Xue, M, Wang, H, Cheng, L, Gao, L, et al. Amplifying the electrical hybridization signals of DNA array by multilayer assembly of Au nanoparticle probes Analyst 2003, 128(7): 917–923.
Velev, OD, Kaler, EW. In situ assembly of colloidal particles into miniaturized biosensors Langmuir 1999, 15(11): 3693–3698.
Cheng, YT, Pun, CC, Tsai, CY, Chen, PH. An array‐based CMOS biochip for electrical detection of DNA with multilayer self‐assembly gold nanoparticles Sens Actuators B Chem 2005, 109(2): 249–255.
Cheng, YT, Tsai, CY, Chen, PH. Development of an integrated CMOS DNA detection biochip Sens Actuators B Chem 2007, 120(2): 758–765.
Chang, TL, Tsai, CY, Sun, CC, Chen, CC, Kuo, LS, et al. Ultrasensitive electrical detection of protein using nanogap electrodes and nanoparticle‐based DNA amplification Biosens Bioelectron 2007, 22(12): 3139–3145.
Nam, JM, Thaxton, CS, Mirkin, CA. Nanoparticle‐based bio‐bar codes for the ultrasensitive detection of proteins Science 2003, 301(5641): 1884–1886.
Urban, M, Moller, R, Fritzsche, W. A paralleled readout system for an electrical DNA‐hybridization assay based on a microstructured electrode array Rev Sci Instrum 2003, 74(2): 1077–1081.
Dequaire, M, Degrand, C, Limoges, B. An electrochemical metalloimmunoassay based on a colloidal gold label Anal Chem 2000, 72(22): 5521–5528.
Authier, L, Grossiord, C, Brossier, P, Limoges, B. Gold nanoparticle‐based quantitative electrochemical detection of amplified human cytomegalovirus DNA using disposable microband electrodes Anal Chem 2001, 73(18): 4450–4456.
Wang, J, Polsky, R, Xu, DK. Silver‐enhanced colloidal gold electrochemical stripping detection of DNA hybridization Langmuir 2001, 17(19): 5739–5741.
Wang, J. Stripping Analysis: Principles, Instrumentation and Applications. Deerfield Beach: VCH Publishers 1985.
Rochelet‐Dequaire, M, Limoges, B, Brossier, P. Subfemtomolar electrochemical detection of target DNA by catalytic enlargement of the hybridized gold nanoparticle labels Analyst 2006, 131(8): 923–929.
Kawde, AN, Wang, J. Amplified electrical transduction of DNA hybridization based on polymeric beads loaded with multiple gold nanoparticle tags Electroanalysis 2004, 16(1–2): 101–107.
Wang, J, Polsky, R, Merkoci, A, Turner, KL. “Electroactive beads” for ultrasensitive DNA detection Langmuir 2003, 19(4): 989–991.
Wang, J, Liu, G, Merkoci, A. Electrochemical coding technology for simultaneous detection of multiple DNA targets J Am Chem Soc 2003, 125(11): 3214–3215.
Hansen, JA, Mukhopadhyay, R, Hansen, JO, Gothelf, KV. Femtomolar electrochemical detection of DNA targets using metal sulfide nanoparticles J Am Chem Soc 2006, 128(12): 3860–3861.
Liu, G, Wang, J, Kim, J, Jan, MR, Collins, GE. Electrochemical coding for multiplexed immunoassays of proteins Anal Chem 2004, 76(23): 7126–7130.
Hansen, JA, Wang, J, Kawde, AN, Xiang, Y, Gothelf, KV, et al. Quantum‐dot/aptamer‐based ultrasensitive multi‐analyte electrochemical biosensor J Am Chem Soc 2006, 128(7): 2228–2229.
Chumbimuni‐Torres, KY, Dai, Z, Rubinova, N, Xiang, Y, Pretsch, E, et al. Potentiometric biosensing of proteins with ultrasensitive ion‐selective microelectrodes and nanoparticle labels J Am Chem Soc 2006, 128(42):): 13676–13677.
Thurer, R, Vigassy, T, Hirayama, M, Wang, J, Bakker, E, et al. Potentiometric immunoassay with quantum dot labels Anal Chem 2007, 79(13): 5107–5110.
Pumera, M, Castaneda, MT, Pividori, MI, Eritja, R, Merkoci, A, et al. Magnetically trigged direct electrochemical detection of DNA hybridization using Au‐67 quantum dot as electrical tracer Langmuir 2005, 21(21): 9625–9629.
Polsky, R, Gill, R, Kaganovsky, L, Willner, I. Nucleic acid‐functionalized Pt nanoparticles: catalytic labels for the amplified electrochemical detection of biomolecules Anal Chem 2006, 78(7): 2268–2271.
Bard, A, Mirkin, M. Scanning Electrochemical Microscopy. New York: Marcel Dekker; 2001.
Wang, J, Song, FY, Zhou, FM. Silver‐enhanced imaging of DNA hybridization at DNA microarrays with scanning electrochemical microscopy Langmuir 2002, 18(17): 6653–6658.
Zhou, XC, O`Shea, SJ, Li, SFY. Amplified microgravimetric gene sensor using Au nanoparticle modified oligonucleotides Chem Commun 2000, 11: 953–954.
Henne, WA, Doorneweerd, DD, Lee, J, Low, PS, Savran, C. Detection of folate binding protein with enhanced sensitivity using a functionalized quartz crystal microbalance sensor Anal Chem 2006, 78(14): 4880–4884.
Zhao, HQ, Lin, L, Li, JR, Tang, JA, Duan, MX, et al. DNA biosensor with high sensitivity amplified by gold nanoparticles J Nanopart Res 2001, 3(4): 321–323.
Liu, T, Tang, J, Zhao, HQ, Deng, YP, Jiang, L. Particle size effect of the DNA sensor amplified with gold nanoparticles Langmuir 2002, 18(14): 5624–5626.
Nie, LB, Yang, Y, Li, S, He, NY. Enhanced DNA detection based on the amplification of gold nanoparticles using quartz crystal microbalance Nanotechnology 2007, 18(30): 305501.
Chu, X, Zhao, ZL, Shen, GL, Yu, RQ. Quartz crystal microbalance immunoassay with dendritic amplification using colloidal gold immunocomplex Sens Actuators B Chem 2006, 114(2): 696–704.
Weizmann, Y, Patolsky, F, Willner, I. Amplified detection of DNA and analysis of single‐base mismatches by the catalyzed deposition of gold on Au‐nanoparticles Analyst 2001, 126(9): 1502–1504.
Pang, L, Li, J, Jiang, J, Shen, G, Yu, R. DNA point mutation detection based on DNA ligase reaction and nano‐Au amplification: a piezoelectric approach Anal Biochem 2006, 358(1): 99–103.
Mao, XL, Yang, LJ, Su, XL, Li, YB. A nanoparticle amplification based quartz crystal microbalance DNA sensor for detection of Escherichia coli O157 : H7 Biosens Bioelectron 2006, 21(7): 1178–1185.
Ma, ZF, Wu, JL, Zhou, TH, Chen, ZH, Dong, YG, et al. Detection of human lung carcinoma cell using quartz crystal microbalance amplified by enlarging Au nanoparticles in vitro New J Chem 2002, 26(12): 1795–1798.
Su, M, Li, SU, Dravid, VP. Microcantilever resonance‐based DNA detection with nanoparticle probes Appl Phys Lett 2003, 82(20): 3562–3564.
Shekhawat, G, Tark, SH, Dravid, VP. MOSFET‐Embedded microcantilevers for measuring deflection in biomolecular sensors Science 2006, 311(5767): 1592–1595.
Bui, MP, Baek, TJ, Seong, GH. Gold nanoparticle aggregation‐based highly sensitive DNA detection using atomic force microscopy Anal Bioanal Chem 2007, 388(5–6): 1185–1190.

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts