Nano-bio Hybrid Materials for a New Generation of High-throughput Diagnostic Systems

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Nano-bio Hybrid Materials for a New Generation of High-throughput Diagnostic Systems

Igor Nabiev

To cite this version:

Igor Nabiev. Nano-bio Hybrid Materials for a New Generation of High-throughput Diagnostic Systems.

Physics Procedia, Elsevier, 2015, 73, pp.95-99. �10.1016/j.phpro.2015.09.127�. �hal-03112346�

Physics Procedia 73 ( 2015 ) 95 – 99

1875-3892 © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Peer-review under responsibility of the National Research Nuclear University MEPhI (Moscow Engineering Physics Institute) doi: 10.1016/j.phpro.2015.09.127

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© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Peer-review under responsibility of the National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)

96 Igor Nabiev / Physics Procedia 73 ( 2015 ) 95 – 99 the recently p

the range of (2014)).

Fig. 1. The B4 ( nanoparticles as capture/recognit

2. Experi When QD DNA oligon bioconjugatio groups (Bila biomolecules in vivo imag modification of -SH group

In the sec incorporated protein with domain, for b depend on b interaction ef to the possib

As a third biotinylated p molecule can F(ab')2 doma oriented conj of capture mo

An altern tagged with manner, with (2014)). Suc sdAbs on the biomarker-ex analysis of th quality than bright multip The sdAb–Q FRET-based

proposed B4 f their applica

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imental part Ds are used for nucleotide or on may be ach an et al. (201 s and is the m ging. In contr ns are often re ps, sulfhydryl cond procedu charged dom a positively binding to the both the chem

fficiency. The le interference d procedure, proteins, nota nnot be easily ains facing in jugates of full olecules with ative approac nanoparticles h all binding h nanoprobes e surface of ea xpressing cell hick tissues no

that obtained photon nanopr QD nanoprobe detection plat

principle for ations (Mahmo

gnosis) approach bels, (2) the best s nd (4) the best con

r molecular or aptamer, ant hieved by cro 15)). The firs most commonl

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ely charged pr reptavidin–bio ted Abs. It sho and may lead moud et al. ( d nanocrystals

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ach to making ps are known tion via these fixed outward n between QD application of main is used lectrostatic int e ambient tem de in this way

roteins.

otin interactio ould be noted d, e.g., to pro (2011) have p s of different the surface of etically modif acid residue f the nanopart

eter below 12 ellent specifici The higher d al Abs and lea mmunohistoch imination of C ous implicatio

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nic diagnostic pro particle transfer to ognition molecul

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ase, the orient D-labelled Ab optimized pro mpositions ens

s after their co omain antibod n their C-term (Sukhanova e four homogen ivity in the qu

f sdAbs enab opsy labeling nostics. Additi ressing tumor throughput m

robes (Fig. 1) et al. (2012);

udes the selection ase, (3) the best

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yed to couple t e first proced arboxylic acid valent linkag or in vitro cell sence of oxyg to the specifi pecific Ab frag molecules or

pling with Ab o the QD, and nding energies

ze can strong or ex vivo cel –streptavidin c ntation of the b Abs with the t ocedure for p suring a high onjugation (Fi dies (sdAbs), minus, in a hi et al. (2012);

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may increase Hafian et al.

n of (1) the best gether.

them with the dure, efficient or sulfhydryl ge of QDs to l labeling and gen, chemical ic localization gments.

proteins with bs, an adaptor d a protein G s considerably gly affect the l labeling due coupling with bound capture target-specific preparation of concentration ig. 2).

which can be ighly oriented Hafian et al.

nted copies of tection of rare histochemical or even better conjugates are normal tissue.

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l for conjugation (BSs) remain inta Ds with Ab fragm

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(2006); Stsia maging and q dimensional g h array locati the use of su er planar array of microbead probe. Each of the probe m can, in turn d can move in say. Hence, w ding schemes.

ng or removin ng kinetics an

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with various operties. How hores. Organic detection in th fluorophore is

of antibodies (Ab act, which ensure ments (3) yields na Adapted fr

v (2008)) and s apura et al. (2 quantifying of rids of probe ion acting as uspension of ys in terms of ds in separate set of microb molecules a , be identifie n any direction

whereas plan . In contrast to ng microbead d facilitated s atistical scrutin ls, dye-tagged of fluorophor hotobleaching ignal. As the

capture mole wever, the use c dyes are sen he presence of

characterized

bs) and nanoparti es the highest affi anoprobes with im from Mahmoud et

suspension (a 2004); Brazhn f entities ava

molecules (A s a probe for optically enc f the way they batches using beads contains attached to th d in the sam n, the type of nar arrays rely

o planar array ds with some

separation ste iny of the data d fluorescent res within the g, quenching

fluorophores ecules, such e of microbea nsitive to pho f background f d by its specifi

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t al. (2011).

lso referred to nik et al. (201 ilable in crud Abs, oligonuc

r a known ta coded polyme y are produced g a variety of

s an individua heir surface. T

e way as the f code used in y strictly on ys, microbead or other pro ep. When man a is possible, w beads (Fig. 3 e microbeads agents, and c are inside the as Abs, and t ads tagged wit otobleaching,

fluorescence.

ic optimal wav

ots, QDs). In the gate. Ab reductio nality of ligand-sp

o as particle-b 15) are the tw de biological leotides, cand arget molecul eric microbea d and used. In proven chemi al optical cod The probes b molecules b multiplexed a positional en assays are flex bes. The mic ny microbead which ensures ) have a sign Additionally changes in pH e beads, surfac

the conjugatio th organic dy and they are Moreover, the velength of ex

conjugates obtain on is made with re pecific recognitio

based) arrays ( wo common a

probes. The didate drugs,

le. The suspe ads. The mic ndeed, probe m

istries under t de (color com being identifie bound to 2D p assays is fixed ncoding, susp exible and allo crobead array ds are used fo

high-quality nificantly brig y, the bead m H and ionic s ce groups on on step does yes suffers fro often not brig eir fluorescen xcitation, whic

ned using this educing agents

n and binding.

(Sukhanova et approaches to planar array etc.) onto flat ension arrays robeads have molecules can the conditions mbination) that ed, the target planar arrays.

d and remains ension arrays ow for an easy provides the or each target

results.

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98 Igor Nabiev / Physics Procedia 73 ( 2015 ) 95 – 99 multiplexing

extremely hi and have ide without over

Fig. 3. QD-en QDs with red spectrum, can shows the distri

Fig. 4. Stabilit

It is worth with unique p without any d

4. Conclu The B4 pr diagnostic na with nanopa nanotoxicity serum album tissues. Thes considered in

Acknowledg This stud Education an

g potential. Th gh brightness eally symmetr rlapping of sig

ncoded beads prep d fluorescence are n penetrate into th

ibution of fluores green line s

ty of QD-encoded

h mentioning parameters. O detectable var

usion rinciple of de anophotonic la articles or wi issues and pr mins (Fleury e se issues shou n a future.

gements dy was suppo nd Science of

he use of QDs s and photosta ric fluorescent gnals from diff

pared by incubatio e located on the s he microbeads. Th scence intensity o

hows this distribu

d beads during th

that the appl Optical propert riation of fluor

velopment of abels with uni ith optically rocesses of int et al. (1997a);

uld be addres

orted by the the Russian F

for tagging m ability, QDs o

t spectra, thus ferent labels (

on of nanoparticl surface of the bea he image on the l of the larger QDs ution for the smal

heir storage for 1 y beads is de

lication of the ties of such be rescence inten

f water-soluble ique optical p

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; Fleury et al.

ssed in full if

Federal Targ ederation (gra

microbeads pe f different co s providing u (Sukhanova et

les of different co ads, whereas the s left shows confoc (with red fluores aller QDs with flu

year in an aqueou etected using flow

e B4-principle eads were pro nsity of beads

e nanoprobes properties base ultiplexed mic nanoparticles w

. (1997b)), up f the applicati

get Program ant no. 14.578

ermits overcom lors can be ex unique possibi

t al. (2007); B

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us solution at +4°

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as detected w

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green region of th

°C. No detectable

velopment of mpletely stable with flow cytom

ay to engineer oriented conju e special atte m proteins (Sh on of the nano particles to in

and Develop ntract no. RFM

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(2015)).

ads. It can be seen n the green region

is conclusion. He m the surface of t the spectrum.

e variation of PL

the diagnosti e at their stora metry (Fig. 4)

ring of a new ugates of captu

ention should hemetov et al.

oparticles in t nvasive diagno

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dition to their on wavelength h microbeads,

n that the larger n of the optical

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References

Bilan, R., Fleury, F., Nabiev, I., Sukhanova, A., 2015. Quantum Dot Surface Chemistry and Functionalization for Cell Targeting and Imaging.

Bioconjugate Chemistry 26, 609-624.

Brazhnik, K., Sokolova, Z., Baryshnikova, M., Bilan, R., Efimov, A., Nabiev, I., Sukhanova, A., 2015, Quantum Dot-Based Lab-on-a-Bead System for Multiplexed Detection of Free and Total Prostate-Specific Antigens in Clinical Human Serum Samples. Nanomedicine: NBM, DOI:

10.1016/j.nano.2015.03.003.

Fleury, F., Kudelina, I., Nabiev, I., 1997a. Interactions of Lactone, Carboxylate and Self-Aggregated Forms of Camptothecin with Human and Bovine Serum Albumins. FEBS Letters 406, 151-156.

Fleury, F., Ianoul, A., Berjot, M., Feofanov, A., Alix, A.J., Nabiev, I., 1997b. Camptothecin-Binding Site in Human Serum Albumin and Protein Transformations Induced by Drug Binding. FEBS Letters 411, 215-220.

Gao, X., Cui, Y., Levenson, R.M., Chung, L.W.K., Nie, S., 2004. In vivo Cancer Targeting and Imaging with Semiconductor Quantum Dots. Nature Biotechnology 22, 969-976.

Hafian, H., Sukhanova, A., Turini, M., Chames, P., Baty, D., Pluot, M., Cohen, J.H.M., Nabiev, I., Millot, J.M., 2014. Multiphoton Imaging of Tumor Biomarkers with Conjugates of Single-Domain Antibodies and Quantum Dots. Nanomedicine: NBM 10, 1701-1709.

Joumaa, N., Lansalot, M., Théretz, A., Elaissari, A., Sukhanova, A., Artemyev, M., Nabiev, I., Cohen, J.H.M., 2006. Synthesis of Quantum Dot- Tagged Submicrometer Polystyrene Particles by Miniemulsion Polymerization. Langmuir 22, 1810-1816.

Mahmoud, W., Sukhanova, A., Oleinikov, V., Rakovich, Yu., Donegan, J.F., Pluot, M., Cohen, J.H.M., Volkov, Yu., Nabiev, I., 2010. Emerging Applications of Fluorescent Nanocrystals Quantum Dots for Micrometastases Detection. Proteomics 10, 700-716.

Mahmud, W., Rousserie, G., Reveil, B., Tabary, T., Millot, J.M., Artemyev, M., Oleinikov, V., Cohen, J.H.M., Nabiev, I., Sukhanova, A. 2011.

Advanced Procedures for Labeling of Antibodies with Quantum Dots. Analytical Biochemistry 416, 180-185.

Montenegro, J.M., Grazu, V., Sukhanova, A., Agarwal, S., de la Fuente, J.M., Nabiev, I., Greiner, A., Parak, W.J., 2013. Controlled Antibody/(Bio-) Conjugation of Inorganic Nanoparticles for Targeted Delivery. Advanced Drug Delivery Reviewes 65, 677-688.

Nabiev, I., Williams, Y., Kelleher, D., Moore, R., Gun'ko, Y., Byrne, S., Rakovich, Yu., Donegan, J.F., Sukhanova, A., Conroy, J., Cottell, D., Gaponik, N., Rogach, A., Volkov, Y., 2007. Nonfunctionalized Nanocrystals Can Exploit a Cell's Active Transport Machinery Delivering Them To Specific Nuclear and Cytoplasmic Compartments. Nano Letters 7, 3452-3461.

Rousserie, G., Sukhanova, A., Even, K., Fleury, F., Chames, P., Baty, D., Oleinikov, V., Pluot, M., Cohen, J.H.M., Nabiev, I., 2010. Semiconductor Quantum Dots for Multiplexed Bio-Detection on Solid-State Microarrays. Critical Reviews Oncology Hematology 74, 1-15.

Samokhvalov, P., Artemyev, M., Nabiev, I., 2013. Basic Principles and Current Trends in Colloidal Synthesis of Highly Luminescent Semiconductor Nanocrystals. Chemistry – A European Journal, 19, 1534-1546.

Shemetov, A.A., Nabiev, I., Sukhanova, A., 2012. Molecular Interaction of Proteins and Peptides with Nanoparticles. ACS NANO 6, 4585-4602.

Stsiapura, V., Sukhanova, A., Artemyev, M., Pluot, M., Cohen, J.H.M., Baranov, A., Oleinikov, V., Nabiev, I., 2004. Functionalized Nanocrystal- Tagged Fluorescent Polymer Beads: Synthesis, Physicochemical Characterization, and Immunolabeling Application. Analytical Biochemistry 334, 257-265.

Sukhanova, A., Venteo, L., Devy, J., Artemyev, M., Oleinikov, V., Pluot, M., Nabiev, I., 2002. Highly Stable Fluorescent Nanocrystals as a Novel Class of Labels for Immunohistochemical Analysis of Paraffin-Embedded Tissue Sections. Laboratory Investigations 82, 1259-1262.

Sukhanova, A., Devy, J., Venteo, L., Kaplan, H., Artemyev, M., Oleinikov, V., Klinov, D., Pluot, M., Cohen, J.H.M., Nabiev, I., 2004. Biocompatible Fluorescent Nanocrystals for Immunolabeling of Membrane Proteins and Cells. Analytical Biochemistry 324, 60-67.

Sukhanova, A., Susha, A., Bek, A., Mayilo, S., Rogach, A., Feldmann, J., Oleinikov, V., Reveil, B., Donvito, B., Cohen, J.H.M., Nabiev, I., 2007.

Nanocrystal-Encoded Fluorescent Microbeads for Proteomics: Antibody Profiling and Diagnostics of Autoimmune Diseases. Nano Letters 7, 2322-2327.

Sukhanova, A., Nabiev, I., 2008. Fluorescent Nanocrystal-Encoded Microbeads for Multiplexed Cancer Imaging and Diagnosis. Critical Reviews Oncology Hematology 68, 39-59.

Sukhanova, A., Even-Desruleaux, K., Kisserli, A., Tabary, T., Reveil, B., Millot, J.M., Chames, P., Baty, D., Artemyev, M., Oleinikov, V., Pluot, M.,

Cohen, J.H.M., Nabiev, I., 2012. Oriented Conjugates of Single-Domain Antibodies and Quantum Dots: Toward a New Generation of Ultrasmall

Diagnostic Nanoprobes. Nanomedecine: NBM 8, 516-525.