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In situ kinetics study of the formation of organic nanoparticles by fluorescence lifetime imaging microscopy (FLIM) along a microfluidic device

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Abstract

In this study, a three-dimensional hydrodynamic focusing microfluidic method is presented that allows full control of the nano-precipitation process of adamantyl mesityl BODIPY (4,4-difluoro-3,5-di-(adamantyl)-8-mesityl-4-bora-3a,4a-diaza-s-indacene) (Adambodipy). The precipitation is achieved by combining a central Adambodipy organic flow with a mixture of water and a cationic surfactant, creating a non-solvent precipitation method. The flow and mixing were simulated using COMSOL Multiphysics® 3.4. A good agreement between theory and experiment was obtained for the flow velocity, concentration fields and the subsequent precipitation kinetics. Fluorescence lifetime imaging was used to visualize the precipitation domains following the changes in fluorescence lifetime. The lifetime decreases from 6.1 ns for the molecules down to 0.9 ns for nanoparticles. A principal components analysis of the successive fluorescence decay curves showed that the process could be adequately modeled using three components, which can be attributed to monomers (single molecule), clusters (nuclei) and nanoparticles.

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Abbreviations

BODIPY:

4,4-Difluoro-4-bora-3a, 4a-diaza-s-indacene

CTACl:

Hexadecyltrimethylammonium chloride

DLS:

Dynamic light scattering

E/EtOH:

Ethanol

FLIM:

Fluorescence lifetime imaging

FONs:

Fluorescent organic nanoparticles

ID:

Inner diameter of the channel

MEMS:

Microelectromechanical systems

MFD:

Micro-fluidic-device

NPs:

Nanoparticles

OD:

Outside diameter

PDMS:

Polydimethylsiloxane

ROI:

Region of interest

THF:

Tetrahydrofuran

ϕ :

Quantum yield

\(\nabla\) :

Del operator

\(\nabla c\) :

Concentration gradient

μ :

Viscosity

ρ :

Fluid density

a :

Particle size, radius

a 0 :

Diffusion length of exciton

d Q :

Density of quenching sites

D ij :

Maxwell–Stefan binary diffusion coefficient

f :

Molar volume fraction of EtOH in the mixture

J :

Jouyban–Acree factor

k F :

Fluorescence rate

k Q :

Quenching rate

M :

Total average molar mass of the mixture (kg/mol)

N :

Avogadro’s number

n 0 :

Refractive index

n(a):

Number of quenching sites

P :

Pressure

ΔP :

Pressure drop

Q (C, S) :

Volumetric flow rate (C = center, S = side)

S :

Supersaturation

U :

Local velocity of the fluid

V :

Molar volume

w :

Mass fraction

W :

Water

x i :

Mole fraction of species i

References

  • Abraham FF (1974) Homogeneous nucleation theory. Academic Press, New York

    Google Scholar 

  • Baba K, Kasai H, Okada S, Oikawa H, Nakanishi H (2003) Fabrication of organic nanocrystals using microwave irradiation and their optical properties. Opt Mater 21(1–3):591–594. doi:10.1016/S0925-3467(02)00206-9

    Article  Google Scholar 

  • Badre S, Monnier V, Meallet-Renault R, Dumas-Verdes C, Schmidt EY, Mikhaleva AI, Laurent G, Levi G, Ibanez A, Trofimov BA, Pansu RB (2006) Fluorescence of molecular micro and nanocrystals prepared with Bodipy derivatives. J Photochem Photobiol A 183(3):238–246. doi:10.1016/j.jphotochem.2006.07.002

    Article  Google Scholar 

  • Boreham A, Kim TY, Spahn V, Stein C, Mundhenk L, Gruber AD, Haag R, Welker P, Licha K, Alexiev U (2011) Exploiting fluorescence lifetime plasticity in FLIM: target molecule localization in cells and tissues. ACS Med Chem Lett 2(10):724–728. doi:10.1021/Ml200092m

    Article  Google Scholar 

  • Calleja V, Ameer-Beg SM, Vojnovic B, Woscholski R, Downward J, Larijani B (2003) Monitoring conformational changes of proteins in cells by fluorescence lifetime imaging microscopy. Biochem J 372(1):33–40. doi:10.1042/BJ20030358

    Article  Google Scholar 

  • Chung HR, Kwon E, Kawa H, Kasai H, Nakanishi H (2006) Effect of solvent on organic nanocrystal growth using the reprecipitation method. J Cryst Growth 294(2):459–463. doi:10.1016/j.jcrysgro.2006.07.010

    Article  Google Scholar 

  • Darken LS (1948) Diffusion, mobility and their interrelation through free energy in binary metallic systems. T Am I Min Met Eng 175:184–201. doi:10.1007/s11661-010-0177-7

    Google Scholar 

  • Génot V, Desportes S, Croushore C, Lefèvre J-P, Pansu RB, Delaire JA, von Rohr PR (2010) Synthesis of organic nanoparticles in a 3D flow focusing microreactor. Chem Eng J 161(1–2):234–239. doi:10.1016/j.cej.2010.04.029

    Article  Google Scholar 

  • Guevara-Carrion G, Nieto-Draghi C, Vrabec J, Hasse H (2008) Prediction of transport properties by molecular simulation: methanol and ethanol and their mixture. J Phys Chem B 112(51):16664–16674. doi:10.1021/jp805584d

    Article  Google Scholar 

  • Harrison DJ, Fluri K, Seiler K, Fan ZH, Effenhauser CS, Manz A (1993) Micromachining a miniaturized capillary electrophoresis-based chemical-analysis system on a chip. Science 261(5123):895–897. doi:10.1126/science.261.5123.895

    Article  Google Scholar 

  • Hessel V, Lowe H, Schonfeld F (2005) Micromixers—a review on passive and active mixing principles. Chem Eng Sci 60(8–9):2479–2501. doi:10.1016/J.Ces.2004.11.033

    Article  Google Scholar 

  • Hibara A, Nonaka M, Tokeshi M, Kitamori T (2003) Spectroscopic analysis of liquid/liquid interfaces in multiphase microflows. J Am Chem Soc 125(49):14954–14955. doi:10.1021/ja037308l

    Article  Google Scholar 

  • Holz M, Heil SR, Sacco A (2000) Temperature-dependent self-diffusion coefficients of water and six selected molecular liquids for calibration in accurate H-1 NMR PFG measurements. Phys Chem Chem Phys 2(20):4740–4742. doi:10.1039/B005319H

    Article  Google Scholar 

  • Jouyban A, Acree WE (2006) In silico prediction of drug solubility in water–ethanol mixtures using Jouyban–Acree model. J Pharm Pharm Sci 9(2):262–269. doi:10.1691/ph.2007.1.6057

    Google Scholar 

  • Kakuta M, Hinsmann P, Manz A, Lendl B (2003a) Time-resolved Fourier transform infrared spectrometry using a microfabricated continuous flow mixer: application to protein conformation study using the example of ubiquitin. Lab Chip 3(2):82–85. doi:10.1039/B302295a

    Article  Google Scholar 

  • Kakuta M, Jayawickrama DA, Wolters AM, Manz A, Sweedler JV (2003b) Micromixer-based time-resolved NMR: applications to ubiquitin protein conformation. Anal Chem 75(4):956–960. doi:10.1021/ac026076q

    Article  Google Scholar 

  • Kamholz AE, Schilling EA, Yager P (2001) Optical measurement of transverse molecular diffusion in a microchannel. Biophys J 80(4):1967–1972. doi:10.1016/S0006-3495(01)76166-8

    Article  Google Scholar 

  • Khattab IS, Bandarkar F, Fakhree MAA, Jouyban A (2012) Density, viscosity, and surface tension of water plus ethanol mixtures from 293 to 323 K. Korean J Chem Eng 29(6):812–817. doi:10.1007/s10953-014-0257-1

    Article  Google Scholar 

  • Knight JB, Vishwanath A, Brody JP, Austin RH (1998) Hydrodynamic focusing on a silicon chip: mixing nanoliters in microseconds. Phys Rev Lett 80(17):3863–3866. doi:10.1103/PhysRevLett.80.3863

    Article  Google Scholar 

  • Kuhn HFH-D, Waldeck DH (2009) Principles of physical chemistry, vol 14. Wiley, Hoboken

    Google Scholar 

  • Li XY, Liu HJ, Sun XX, Bi GQ, Zhang GQ (2013) Highly fluorescent dye-aggregate-enhanced energy-transfer nanoparticles for neuronal cell imaging. Adv Opt Mater 1(8):549–553. doi:10.1002/adom.201300173

    Article  Google Scholar 

  • Liao Y-Y, Génot V, Meallet-Renault R, Vu TT, Audibert JF, Lemaistre JP, Clavier G, Retailleau P, Pansu RB (2013) Spectroscopy of BODIPY in solid phase: crystal and nanoparticles. Phys Chem Chem Phys 15(9):3186–3195. doi:10.1039/c2cp43289g

    Article  Google Scholar 

  • Lin HJ, Herman P, Lakowicz JR (2003) Fluorescence lifetime-resolved pH imaging of living cells. Cytometry A 52(2):77–89. doi:10.1002/cyto.a.10028

    Article  Google Scholar 

  • Meallet-Renault R, Herault A, Vachon JJ, Pansu RB, Amigoni-Gerbier S, Larpent C (2006) Fluorescent nanoparticles as selective Cu(II) sensors. Photochem Photobiol Sci 5(3):300–310. doi:10.1039/B513215K

    Article  Google Scholar 

  • Nielsen AE (1964) Kinetics of precipitation. Pergamon Press, New York

    Google Scholar 

  • Ofuji M, Lovinger AJ, Kloc C, Siegrist T, Maliakal AJ, Katz HE (2005) Organic semiconductor designed for lamination transfer between polymer films. Chem Mater 17(23):5748–5753. doi:10.1021/Cm0516w

    Article  Google Scholar 

  • Roth CM, Heinlein PI, Heilemann M, Herten DP (2007) Imaging diffusion in living cells using time-correlated single-photon counting. Anal Chem 79(19):7340–7345. doi:10.1021/Ac071039q

    Article  Google Scholar 

  • Spitz JA, Yasukuni R, Sandeau N, Takano M, Vachon JJ, Meallet-Renault R, Pansu RB (2008) Scanning-less wide-field single-photon counting device for fluorescence intensity, lifetime and time-resolved anisotropy imaging microscopy. J Micros-Oxford 229(1):104–114. doi:10.1111/j.1365-2818.2007.01873.x

    Article  MathSciNet  Google Scholar 

  • Su YF, Kim H, Kovenklioglu S, Lee WY (2007) Continuous nanoparticle production by microfluidic-based emulsion, mixing and crystallization. J Solid State Chem 180(9):2625–2629. doi:10.1016/j.jssc.2007.06.033

    Article  Google Scholar 

  • Teixeira R, Andrade SM, Serra VV, Paulo PMR, Sanchez-Coronilla A, Neves MGPMS, Cavaleiro JAS, Costa SMB (2012) Reorganization of self-assembled dipeptide porphyrin J-aggregates in water–ethanol mixtures. J Phys Chem B 116(8):2396–2404. doi:10.1021/jp2115719

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank the EDSP (École Doctorale Sciences Pratiques) of ENS (École Normale Supérieure) of Cachan for funding the Ph.D. thesis of Y–Y.L.

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Author notes

  1. Yuanyuan Liao

    Present address: UMR 5182 du CNRS, ENS-Lyon, 46 Allee d’Italie, 69364, Lyon Cedex 07, France

Authors and Affiliations

  1. Laboratoire PPSM, UMR 8531 du CNRS, ENS-Cachan, 61 av. Pdt Wilson, 94230, Cachan, France

    Yuanyuan Liao, Valérie Génot, Jean-Frédéric Audibert & Robert B. Pansu

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  1. Yuanyuan Liao
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  2. Valérie Génot
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  3. Jean-Frédéric Audibert
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  4. Robert B. Pansu
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Correspondence to Yuanyuan Liao.

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Liao, Y., Génot, V., Audibert, JF. et al. In situ kinetics study of the formation of organic nanoparticles by fluorescence lifetime imaging microscopy (FLIM) along a microfluidic device. Microfluid Nanofluid 20, 59 (2016). https://doi.org/10.1007/s10404-016-1721-6

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