Diagnostic Nanotechnologies


Diagnostic Nanotechnologies

Dhanya K. Chandrasekharan, Dani Mathew M., Elizabeth P. Thomas

The application of nanotechnology in clinical diagnostic purposes can be defined as nanodiagnostics. Since most of the biological molecules as well as cell organelles fall within the nano scale, nanotechnology can assure to meet the rigorous demands being put forth by the clinical laboratory in terms of sensitivity, earlier and faster detection of diseases and cost-effectiveness. Nanotechnology Based Diagnostics or Nanodiagnostics is also termed as “molecular imaging” and it is an evolutionary leap in diagnostic imaging. Nanodiagnostics assays are utilized in immunoassays, DNA diagnostics, imaging, etc for the detection of tumors and infectious diseases.

Nanodiagnostics, Nanoparticles, Theranostics, Nanotechnology, Cancer

Published online 2/10/2024, 18 pages

Citation: Dhanya K. Chandrasekharan, Dani Mathew M., Elizabeth P. Thomas, Diagnostic Nanotechnologies, Materials Research Foundations, Vol. 160, pp 145-162, 2024

DOI: https://doi.org/10.21741/9781644902974-6

Part of the book on Nanoparticles in Healthcare

[1] Jain K K. Nanotechnology in clinical laboratory diagnostics. Clin Chim Acta 358 (2005) [37–54]. https://doi.org/10.1016/j.cccn.2005.03.014
[2] Jain K K. Nanodiagnostics: application of nanotechnology in molecular diagnostics. Expert Rev Mol Diagn 3 (2003) [153–161]. https://doi.org/10.1586/14737159.3.2.153
[3] West J L, Halas N J. Engineered nanomaterials for biophotonics applications: improving sensing, imaging, and therapeutics. Annu Rev Biomed Eng 5 (2003) [285–292]. https://doi.org/10.1146/annurev.bioeng.5.011303.120723
[4] Hassan M.E. Azzazy, Mai M.H. Mansour, and Steven C. Kazmierczak, Nanodiagnostics: A New Frontier for Clinical Laboratory Medicine, Clinical Chemistry 52 (2006) [1238–1246]. https://doi.org/10.1373/clinchem.2006.066654
[5] Groneberg D A; Giersig M, Welte T, Pison U, Nanoparticle-Based Diagnosis and Therapy, Current Drug Targets 7 (2006) [643-648]. https://doi.org/10.2174/138945006777435245
[6] Elghanian R, Storhoff J J, Mucic R C, Letsinger R L, Mirkin C A. Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. Science 277 (1997) [1078–1081]. DOI: 10.1126/science.277.5329.1078
[7] Liu J and Lu Y. A colorimetric lead biosensor using DNAzyme-directed assembly of gold nanoparticles. J. Am. Chem. Soc. 125 (2003) [6642–6643]. https://doi.org/10.1021/ja034775u
[8] Alivisatos P. The use of nanocrystals in biological detection. Nat Biotechnol 22 (2004) [47–52]. https://doi.org/10.1038/nbt927
[9] Rosi N L, Mirkin C A. Nanostructures in biodiagnostics. Chem Rev 105 (2005) [1547–1562]. https://doi.org/10.1021/cr030067f
[10] Dwaine F. Emerich and Christopher G. T, The pinpoint promise of nanoparticle-based drug delivery and molecular diagnosis, Biomolecular Engineering 23 (2006) [171-184]. https://doi.org/10.1016/j.bioeng.2006.05.026
[11] Link S, and El-Sayed M, Spectral properties and relaxation dynamics of surface plasmon electronic oscillations in gold and silver nanodots and nanorods. J. Phys. Chem. B 103, (1999) [8410-8426]. https://doi.org/10.1021/jp9917648
[12] Kelly K L, Coronado E, Zhao L.L, and Schatz G C, The optical properties of metal nanoparticles: the influence of size, shape, and dielectric environment. J. Phys. Chem. B 107 (2003) [668-677]. https://doi.org/10.1021/jp026731y
[13] Jensen T R, Schatz G C, and Van Duyne R P, Nanosphere lithography: surface plasmon resonance spectrum of a periodic array of silver nanoparticles by ultraviolet-visible extinction spectroscopy and electrodynamic modeling. J. Phys. Chem. B 103 (1999) [2394-2401]. https://doi.org/10.1021/jp984406y
[14] Jiang X, Jiang J, Jin Y, Wang E, and Dong S, Effect of colloidal gold size on the conformational changes of adsorbed cytochrome c: probing by circular dichroism, UV-visible, and infrared spectroscopy. Biomacromolecules, (2005) [46-53]. https://doi.org/10.1021/bm049744l
[15] Azzazy HME, Mansour MMH, In vitro diagnostic prospects of nanoparticles, Clinica Chimica Acta 403 (2009) [1-8]. https://doi.org/10.1016/j.cca.2009.01.016
[16] Brigger I, Dubernet C, Couvreur P, Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 54 (2002) [631-651]. https://doi.org/10.1016/j.addr.2012.09.006
[17] Cuenca AG, Jiang H, Hochwald SN, Delano M, Cance WG, Grobmyer SR: Emerging implications of nanotechnology on cancer diagnostics and therapeutics. Cancer 107 (2006) [459-466]. https://doi.org/10.1002/cncr.22035
[18] 113. Zhang Z, Yang X, Zhang Y, Zeng B, Wang S, Zhu T, Roden RB, Chen Y, Yang R: Delivery of telomerase reverse transcriptase small interfering RNA in complex with positively charged single walled carbon nanotubes suppresses tumor growth. Clin Cancer Res 12 (2006) [4933-4939]. https://doi.org/10.1158/1078-0432.CCR-05-2831
[19] Bhattacharya R, Senbanerjee S, Lin Z, Mir S, Hamik A, Wang P, Mukherjee P, Mukhopadhyay D, Jain MK: Inhibition of vascular permeability factor/vascular endothelial growth factor mediated angiogenesis by the Kruppel-like factor KLF2. J Biol Chem 280 (2005) [28848-28851]. https://doi.org/10.1074/jbc.C500200200
[20] Mukherjee P, Bhattacharya R, Wang P, Wang L, Basu S, Nagy JA, Atala A, Mukhopadhyay D, Soker S: Antiangiogenic properties of gold nanoparticles. Clin Cancer Res 11 (2005) [3530-3534]. https://doi.org/10.1158/1078-0432.CCR-04-2482
[21] O’Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL: Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett 209 (2004) [171-176]. https://doi.org/10.1016/j.canlet.2004.02.004
[22] Paciotti GF, Myer L, Weinreich D, Goia D, Pavel N, McLaughlin RE, Tamarkin L: Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery. Drug Deliv 11 (2004) [169-183]. https://doi.org/10.1080/10717540490433895
[23] Kam NW, Liu Z, Dai H: Carbon nanotubes as intracellular transporters for proteins and DNA: an investigation of the uptake mechanism and pathway. Angew Chem Int Ed Engl 45 (2006) [577-581]. https://doi.org/10.1002/anie.200503389
[24] Chan W C, Nie S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281 (1998) [2016–2018]. DOI: 10.1126/science.281.5385.2016
[25] Wu X, Liu H, Liu J, Haley K N, Treadway J A, Larson J P, et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol 21 (2003) [41–46]. https://doi.org/10.1038/nbt764
[26] Azzazy H M E, Mansour M M H. and Kazmierczak S C, Nanodiagnostics: A New Frontier for Clinical Laboratory Medicine, Clinical Chemistry 52 (2006) [1238–1246]. https://doi.org/10.1373/clinchem.2006.066654
[27] Michalet X, Pinaud F F, Bentolila L A, Tsay J M, Doose S, Li J J, et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307 (2005) [538–44]. DOI: 10.1126/science.1104274
[28] Bruchez M, Moronne M, Gin P, Weiss S and Alivisatos AP, Semiconductor nanocrystals as fluorescent biological labels, Science 281 (1998) [2013–2015]. DOI: 10.1126/science.281.5385.2013
[29] Fortina P, Kricka L J, Surrey S, Grodzinski P. Nanobiotechnology: the promise and reality of new approaches to molecular recognition. Trends Biotechnol 23 (2005) [168–173]. https://doi.org/10.1016/j.tibtech.2005.02.007
[30] 41.Han M, Gao X, Su J Z, Nie S. Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat Biotechnol 19 (2001) [631–635]. https://doi.org/10.1038/90228
[31] Larson D R, Zipfel W R, Williams R M, Clark S W, Bruchez M P, Wise F W, et al. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300 (2003) [1434–1436]. DOI: 10.1126/science.1083780
[32] Crut A, Geron-Landre B, Bonnet I, Bonneau S, Desbiolles P, Escude C. Detection of single DNA molecules by multicolor quantum-dot end-labeling. Nucleic Acids Res 33 (2005) e98. https://doi.org/10.1093/nar/gni097
[33] Dubertret B 1, Skourides P, Norris D J, Noireaux V, Brivanlou A H, Libchaber A. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298 (2022) [1759-1762]. DOI: 10.1126/science.1077194
[34] Harma H, Soukka T, Lovgren T. Europium nanoparticles and time-resolved fluorescence for ultrasensitive detection of prostate- specific antigen. Clin Chem 47 (2001) [561–8]. https://doi.org/10.1093/clinchem/47.3.561
[35] Jin T, Fujii F, Sakata H, Tamura M, Kinjo M. Amphiphilic p-sulfonatocalix[4]arene-coated CdSe/ZnS quantum dots for the optical detection of the neurotransmitter acetylcholine. Chem Commun (Camb) (2005) [4300–4302]. https://doi.org/10.1039/B506608E
[36] Akerman M E, Chan W C, Laakkonen P, Bhatia S N, Ruoslahti E. Nanocrystal targeting in vivo. Proc Natl Acad Sci U S A 99 (2002) [12617–12621].
[37] Yeh H C, Ho Y P, Shih I, Wang T H. Homogeneous point mutation detection by quantum dot-mediated two-color fluorescence coincidence analysis. Nucleic Acids Res 34 (2006) e35. https://doi.org/10.1093/nar/gkl021
[38] Schmitt J, Decher G, Dressick W J, Brandow S L, Geer R E, Shashidar R, Calvert J M, AdV. Mater. 9 (1997) [61-65]. https://doi.org/10.1002/adma.19970090114
[39] Mauriz E. Clinical Applications of Visual Plasmonic Colorimetric Sensing. Sensors (Basel) 20. (2020) [6214]. https://doi.org/10.3390/s20216214
[40] de la Fuente A J M, Barrientos A G, Rojas T C, Rojo J, Canada J, Fernamdez A and Penades S, Angew. Chem., Int. Ed., 40 (2001) [2258–2260].
[41] Tsai C, Yu T and Chen C T, Gold nanoparticle-based competitive colorimetric assay for detection of protein–protein interactions Chem. Commun. (2005) [4273–4275]. DOI: 10.1039/B507237A
[42] Storhoff J J, Lazarides A A, Mucic R C, Mirkin Chad A, Letsinger R L and Schatz G C What Controls the Optical Properties of DNA-Linked Gold Nanoparticle Assemblies? J. Am. Chem. Soc. 122 (2000) [4640-4650]. https://doi.org/10.1021/ja993825l
[43] Liu, J and Lu Y. Stimuli-responsive disassembly of nanoparticle aggregates for light-up colorimetric sensing. J. Am. Chem. Soc. 127(2005) [12677–12683]. https://doi.org/10.1021/ja053567u
[44] Liu J and Lu Y Fast colorimetric sensing of adenosine and cocaine based on a general sensor design involving aptamers and nanoparticles. Angew. Chem. Int. Ed. Engl. 45 (2006) [90]. https://doi.org/10.1002/anie.200502589
[45] Huang C C, Huang Y F, Cao Z, Tan W, and Chang H T. Aptamer modified gold nanoparticles for colorimetric determination of platelet derived growth factors and their receptors. Anal. Chem. 77 (2005) [5735–5741]. https://doi.org/10.1021/ac050957q
[46] Guarise C, Pasquato L, Filippis V De, and Scrimin P, Gold nanoparticles-based protease assay, PNAS 103 (2006) [3978–3982]. https://doi.org/10.1073/pnas.0509372103
[47] Chah S, Hammond M R, and Zare R N, Gold Nanoparticles as a Colorimetric Sensor for Protein Conformational Changes, Chemistry & Biology12 (2005) [323-328]. DOI 10.1016/j.chembiol.2005.01.013
[48] Nath N and Chilkoti A, Interfacial phase transition of an environmentally responsive elastin biopolymer adsorbed on functionalized gold nanoparticles studied by colloidal surface plasmon resonance. J. Am. Chem. Soc. 123 (2001], [8197-8202]. https://doi.org/10.1021/ja015585r
[49] Mirkin C A, Letsinger R L, Mucic R C and Storhoff J J, A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382 (1996) [607-609].
[50] Goodrich G P, Helfrich M R, Overberg J J and Keating C D, Effect of macromolecular crowding on DNA:Au nanoparticle bioconjugate assembly. Langmuir 20 (2004) [10246-10251]. https://doi.org/10.1021/la048434l
[51] Maxwell D J, Taylor J R and Nie S, Self-assembled nanoparticle probes for recognition and detection of biomolecules. J. Am. Chem. Soc. 124 (2002) [9606-9612]. https://doi.org/10.1021/ja025814p
[52] Lu Y and Liu J, Accelerated color change of gold nanoparticles assembled by DNAzymes for simple and fast colorimetric Pb2+ detection. J. Am. Chem. Soc. 126 (2004) [12298-12305]. https://doi.org/10.1021/ja046628h
[53] Daniel, M C, and Astruc D, Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem. Rev. 104 (2004) [293-346]. https://doi.org/10.1021/cr030698+
[54] Wang J, Nanoparticle-based electrochemical DNA detection, Analytica Chimica Acta 500 (2003) [247-257]. https://doi.org/10.1016/S0003-2670(03)00725-6
[55] Dykman LA and Khlebtsov NG, Gold Nanoparticles in Biology and Medicine: Recent Advances and Prospects. Acta Naturae 3 (2011) [34–55].
[56] Andrea C, Robert M, Wolfgang F, Elghanian R, Storhoff J J, Mucic R C, Letsinger R L, Mirkin C A. Expert Review of Molecular Diagnostics 2 (2002) [187-193]. https://doi.org/10.1586/14737159.2.2.187
[57] Freeman R G, Grabar K C, Allison K J, Bright R M, Davis J A, Guthrie A P, Hommer M B, Jackson M A, Smith P C, Walter D G, Natan M J. Science 267 (1995) [1629-1632]. DOI: 10.1126/science.267.5204.1629
[58] Sun L, Zhang Z, Wang S, Zhang J, Li H, Ren L, Weng J, Zhang Q. Effect of pH on the Interaction of Gold Nanoparticles with DNA and Application in the Detection of Human p53 Gene Mutation Nanoscale Res Lett 4 (2009) [216–220]. https://doi.org/10.1007/s11671-008-9228-z
[59] Kalogianni DP, Koraki T, Christopoulos TK, Ioannou PC, Nanoparticle-based DNA biosensor for visual detection of genetically modified organisms. Biosensors and Bioelectronics 21 (2006) [1069-1076]. https://doi.org/10.1016/j.bios.2005.04.016
[60] Baptista PV, Koziol-Montewka M, Paluch-Oles J, Doria G, Franco R, Gold-Nanoparticle-Probe–Based Assay for Rapid and Direct Detection of Mycobacterium tuberculosis DNA in Clinical Samples Clinical Chemistry 52 (2006). https://doi.org/10.1373/clinchem.2005.065391
[61] Georganopoulou D G, Chang L, Nam J M, Thaxton C S, Mufson E J, Klein W L, et al. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease. Proc Natl Acad Sci U S A 102 (2005) [2273–2276]. https://doi.org/10.1073/pnas.0409336102
[62] Huang X, Prashant K J , El-Sayed I H and El-Sayed M A, Special Focus: Nanoparticles for Cancer Diagnosis & Therapeutics – Review, Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostics and therapy, Nanomedicine 2 (2007) [681-693]. https://doi.org/10.2217/17435889.2.5.681
[63] El-Sayed I H, Huang X, and El-Sayed M A, Surface Plasmon Resonance Scattering and Absorption of anti-EGFR Antibody Conjugated Gold Nanoparticles in Cancer Diagnostics: Applications in Oral Cancer, Nano Lett. 5 (2005], [829–834]. https://doi.org/10.1021/nl050074e
[64] Huang X, El-Sayed I H, Qian W and El-Sayed M A, Cancer Cell Imaging and Photothermal Therapy in the Near-Infrared Region by Using Gold Nanorods, J. Am. Chem. Soc. 128 (2006) [2115–2120]. https://doi.org/10.1021/ja057254a
[65] Seol Y, Carpenter A E, Perkins T T, Gold nanoparticles: enhanced optical trapping and sensitivity coupled with significant heating, Optics Letters 31 (2006). https://doi.org/10.1364/OL.31.002429
[66] Raj C R, Okajima T and Ohsaka T, Gold nanoparticle arrays for the voltammetric sensing of dopamine, Journal of Electroanalytical Chemistry 543 (2003) [127-133]. https://doi.org/10.1016/S0022-0728(02)01481-X
[67] Simoniana A L, Good T A, Wang S S, and Wild J R Nanoparticle-based optical biosensors for the direct detection of organophosphate chemical warfare agents and pesticides, Analytica Chimica Acta 534 (2005) [69–77]. https://doi.org/10.1016/j.aca.2004.06.056
[68] Chen X, Tam U C, Czlapinski J L, Lee G S, Rabuka D, Zettl A and Bertozzi C R, Interfacing carbon nanotubes with living cells J. Am. Chem. Soc. 128 (2006) [6292–6293]. https://doi.org/10.1021/ja060276s
[69] Yu X, Munge B, Patel V, Jensen G, Bhirde A, Gong JD, Kim SN, Gillespie J, Gutkind JS, Papadimitrakopoulos F, Rusling JF, Carbon nanotube amplification strategies for highly sensitive immunodetection of cancer biomarkers J. Am. Chem. Soc. 128 (2006) [11199–11205]. https://doi.org/10.1021/ja062117e
[70] Josephson L, Tung C H, Moore A and Weissleder R. High-efficiency intracellular magnetic labeling with novel superparamagnetic-tat peptide conjugates, Bioconjugate Chem. 10 (1999) [186–191]. https://doi.org/10.1021/bc980125h
[71] Bulte JWM, Douglas T, Witwer B, Zhang SC, Strable E, Lewis BK, Zywicke H, Miller B, Van Gelderen P, Moskowitz BM, Duncan ID, Frank JA, Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells, Nat. Biotechnol. 19 (2001) [1141–1147]. https://doi.org/10.1038/nbt1201-1141
[72] Gref R, Minamitake Y, Peracchia M T, Trubetskoy V, Torchilin V and Langer R. Biodegradable long-circulating polymeric nanospheres Science 263 (1994) [1600-1603]. DOI: 10.1126/science.8128245
[73] Neuberger T, Schopf B, Hofmann H, Hofmann M and von Rechenberg B. Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system, Journal of Magnetism and Magnetic Materials 293 (2005) [483-496]. https://doi.org/10.1016/j.jmmm.2005.01.064
[74] Lee C, Jeong H, Kim S, Kim E, Kim D W, Lim S T, Jang K Y, Jeong Y Y, Nah J and Sohn M SPION-loaded chitosan–linoleic acid nanoparticles to target hepatocytes, International Journal of Pharmaceutics 371 (2009) [163-169]. https://doi.org/10.1016/j.ijpharm.2008.12.021
[75] Romanus E, Hückel M, Gro C, Prass S, Weitschies W, Brauer R and Weber P. Journal of Magnetism and Magnetic Materials 252 (2002) [387-389]. https://doi.org/10.1016/S0304-8853(02)00645-5
[76] Fortina P, Kricka L J, Graves D J, Park J, Hyslop T, Tam F, Halas N, Surrey S and Scott A. Waldman Applications of nanoparticles to diagnostics and therapeutics in colorectal cancer, Trends in Biotechnology 25 (2007) [145-152]. https://doi.org/10.1016/j.tibtech.2007.02.005
[77] Liu C H, Ren J Q, Yang J, Liu C, Mandeville J B, Rosen B R, Bhide P G, Yanagawa Y, Liu P K. DNA-Based MRI Probes for Specific Detection of Chronic Exposure to Amphetamine in Living Brains J. Neurosci 29 (2009) [10663-10670]. https://doi.org/10.1523/JNEUROSCI.2167-09.2009
[78] Berry CC, Possible exploitation of magnetic nanoparticle–cell interaction for biomedical applications J. Mater. Chem. 15 (2005) [543–547].
[79] Gould P. Nanoparticles probe biosystems, Materials today 7 (2004) [36-43]. DOI10.1016/S1369-7021(04)00082-3
[80] Nam J M, Thaxton C S, Mirkin C A. Nanoparticle-based bio-bar codes for the ultrasensitive detection of proteins. Science 301 (2003) [1884–1886]. DOI: 10.1126/science.1088755
[81] Nam J M, Stoeva S I, Mirkin C A. Bio-bar-code-based DNA detection with PCR-like sensitivity. J Am Chem Soc 126 (2004) [5932–5933]. https://doi.org/10.1021/ja049384+
[82] Taton T A, Mirkin C A, Letsinger R L. Scanometric DNA array detection with nanoparticle probes. Science 289 (2000) [1757–1760]. DOI: 10.1126/science.289.5485.1757
[83] Fradinger E A, Bitan G. En route to early diagnosis of Alzheimer’s disease: are we there yet? Trends Biotechnol 23 (2005) [531–533]. https://doi.org/10.1016/j.tibtech.2005.09.002
[84] Oh B K, Nam J, Lee S W, Mirkin C A. A fluorophore-based biobarcode amplification assay for proteins. Small 2 (2006) [103–108]. https://doi.org/10.1002/smll.200500260
[85] Haes A J and Van Duyne R P. A Nanoscale Optical Biosensor: Sensitivity and Selectivity of an Approach Based on the Localized Surface Plasmon Resonance Spectroscopy of Triangular Silver Nanoparticles, J. Am. Chem. Soc. 124 (2002) [10596–10604]. https://doi.org/10.1021/ja020393x
[86] Abraham A M, Kannangai R, Sridharan G, Nanotechnology: A new frontier in virus detection in clinical practice, Indian Journal of Medical Microbiology 26 (2008) [297-301]. https://doi.org/10.1016/S0255-0857(21)01804-1
[87] Valanne A, Huopalahti S, Soukka T, Vainionpaa R, Lovgren T and Harma H. A sensitive adenovirus immunoassay as a model for using nanoparticle label technology in virus diagnostics Journal of Clinical Virology 33 (2005) [217-223]. https://doi.org/10.1016/j.jcv.2004.11.007
[88] Tripp R A, Alvarez R, Anderson B, Jones L, Weeks C, Chen W. Bioconjugated nanoparticle detection of respiratory syncytial virus infection. Int J Nanomed 2 (2007) [117-124]. https://doi.org/10.2147/IJN.S2.1.117
[89] Tang S, Zhao J, Storhoff J J, Norris P J, Little R F, Yarchoan R, et al . Nanoparticle-Based biobarcode amplification assay (BCA) for sensitive and early detection of human immunodeficiency type 1 capsid (p24) antigen. J Acquir Immune Defic Syndr 46 (2007) [231-237]. DOI: 10.1097/QAI.0b013e31814a554b
[90] McKendry R, Zhang J, Arntz Y, Strunz T, Hegner M, Lang H P, et al. Multiple label-free bio detection and quantitative DNA-binding assays on a nanomechanical cantilever array. Proc Natl Acad Sci U S A 99 (2002) [9783–9788]. https://doi.org/10.1073/pnas.152330199
[91] Taylor J R, Fang M M and Nie S. Probing Specific Sequences on Single DNA Molecules with Bioconjugated Fluorescent Nanoparticles Anal. Chem. 72 (2000) [1979-1986]. https://doi.org/10.1021/ac9913311
[92] Ahrens E T, Flores R, Xu H, Morel P A. In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol. 23 (2005) [983–987]. https://doi.org/10.1038/nbt1121
[93] Neamtu J, Jitaru I, Malaeru T, Georgescu G, Kappel W and Alecu V V Synthesis and Properties of Magnetic Nanoparticles with Potential Applications in Cancer Diagnostic, NSTI Nanotechnology Conference & Trade Show 2005.
[94] Alivisatos P, Johnsson K P, Peng X, Wilson T E, Loweth C J, Bruchez M and Schultz P G, Organization of nanocrystal molecules using DNA, Nature (London) 382 (1996) [609–611]. https://doi.org/10.1038/382609a0
[95] Boal A K, Ilhan F, DeRouchey J E, Thurn-Albrecht T, Russell T P and Rotello V M, Self-assembly of nanoparticles into structured spherical and network aggregates, Nature (London) 404 (2000) [746– 748]. https://doi.org/10.1038/35008037
[96] Templeton A C, Wuelfing M P and Murray R W, Monolayer protected cluster molecules, Acc. Chem. Res. 33 (2000) [27–36]. https://doi.org/10.1021/ar9602664
[97] Mattoussi H, Mauro J M, Goldman E R, Anderson G P, Sundar V C, Mikulec F V and Bawendi M G, Self-assembly of CdSe- ZnS quantum dots bioconjugates using an engineered recombinant protein, J. Am. Chem. Soc. 122 (2000) [12142–12150]. https://doi.org/10.1021/ja002535y
[98] Mitchell P, Turning the spotlight on cellular imaging — Advances in imaging are enabling researchers to track more accurately the localization of macromolecules in cells, Nat. Biotechnol. 19 (2001) [1013– 1017]. https://doi.org/10.1038/nbt1101-1013
[99] Baptista, PV, Nanodiagnostics: Leaving the Research Lab to Enter the Clinics? Diagnosis 1 (2014) [305-309]. https://doi.org/10.1515/dx-2014-0055
[100] Alharbi KK, Al-sheikh YA, Role and implications of nanodiagnostics in the changing trends of clinical diagnosis, Saudi Journal of Biological Sciences 21 (2014) [109-117]. https://doi.org/10.1016/j.sjbs.2013.11.001
[101] Jackson, T, Patani, B. and Ekpa, D, Nanotechnology in Diagnosis: A Review. Advances in Nanoparticles 6 (2017) [93-102]. DOI: 10.4236/anp.2017.63008
[102] Lu, Z.R., Ye, F. and Vaidya, A, Polymer Platforms for Drug Delivery and Biomedical Imaging. Journal of Controlled Release 122 (2007) [269-277]. https://doi.org/10.1016/j.jconrel.2007.06.016
[103] Singh S, Hicham F, Singh B, Nanotechnology, Nanotechnology based drug delivery systems J. Occupat. Med. Toxcol. 2 (2007) [16]. https://doi.org/10.1186/1745-6673-2-16
[104] Lee S, Kwon I C, Kim K, Multifunctional Nanoparticles for Cancer Theragnosis X. Chen (Ed.], Nanoplatform-Based Molecular Imaging, John Wiley & Sons, Inc., Hoboken, NJ, USA (2011). https://doi.org/10.1002/9780470767047.ch22
[105] Moffatt S, Nanodiagnostics: a revolution in biomedical nanotechnology. MOJ Proteomics Bioinform.3 (2016) [34-36]. DOI: 10.15406/ mojpb.2016.03.00080