GOLD NANOPARTICLE-LADEN MICROGELS WITH SELECTIVE
PERMEABILITY FOR SERS APPLICATIONS
Dong Jae Kim1, Tae Yoon Jeon1, Youn-Kyoung Baek2, Sung-Gyu Park1, Dong-Ho Kim2
and Shin-Hyun Kim1*
1
Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science
and Technology (KAIST), Daejeon, Republic of Korea and
2
Advanced Functional Thin Films Department, Korea Institute of Materials Science (KIMS),
Changwon, Republic of Korea
ABSTRACT
We design semipermeable microgels containing gold nanoparticles to directly detect small molecules
in a biological fluid using surface-enhanced Raman scattering. The unifom gold nanoparticle-laden
microgels are formed by capillary microfluidic device. The microgels define a molecular size cut-off and
molecules which size are below cut-off value are permitted. In biological fluid, selective permeation of
small targeting molecules prevent large adhesive proteins from adsorbing on surfaces of gold
nanoparticles. This property enables the direct detection of analytes without pre-treatment of samples for
removing large proteins.
KEYWORDS: Surface enhanced raman, Hydrogel, Microfluidics
INTRODUCTION
Metal nanoparticles or nanostructures enable the strong localization of electromagnetic field on their
surface and provide enhancement of Raman signal for molecules adsorbed on the surface; this is referred
to as surface-enhanced Raman scattering (SERS). Therefore, SERS is promising for detecting unknown
molecules including bioactive chemicals. However, when biological fluids are subjected to SERS
analysis, pre-treatment is prerequisite to exclude large adhesive molecules; otherwise, metal surface is
covered by the adhesive molecules, significantly reducing Raman signal of target molecules. This usually
entails complex dialysis procedure[1], centrifugation[2] and significant dilution or loss of targeting
molecules.
EXPERIMENTAL
Using a capillary microfluidic device, aqueous solution of gel precursors containing gold nanoparticles
is uniformly emulsified in a continuous oil phase as shown in Figure 1. Subsequent UV irradiation
crosslinks the precursors to form microgels, immobilizing the gold nanoparticles in the matrix. The
microgels are then transferred from oil to water.
Figure 1: Schematic image of a capillary microfluidic device
RESULTS AND DISCUSSION
The microgels which are homogeneously crosslinked possess uniform mesh and provide size-selective
permeability. The cut-off value of permeation is determined by crosslinking density which is experimentally
controllable by adjusting precursor concentration as shown in Figure 2.
978-0-9798064-8-3/µTAS 2015/$20©15CBMS-0001
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19th International Conference on Miniaturized
Systems for Chemistry and Life Sciences
October 25-29, 2015, Gyeongju, KOREA
Figure 2: Confocal microscope images of microgels dispersed in fluorescein isothiocyanate(FITC)-dextran. Microgels, prepared from 10 wt% poly(ethylene glycol)diacrylate(PEGDA), have cut-off value between 40k(9 nm) and
70k(12nm). When the PEGDA concentration is adjusted to 30 wt%, cut-off value is between 20k(7 nm) and 40k(9 nm).
Microgels, prepared from 70 wt% PEGDA, have cut-off value between 10k(5 nm) and 20k(7 nm). (scale bar, 50 μm)
Therefore, gold nanoparticle-laden microgels allow diffusion of smaller molecules than mesh size,
while excluding larger molecules. This enables selective exclusion of large adhesive protein molecules and
SERS analysis of small molecules without sample pretreatment. To demonstrate this, we first evaluate
SERS activity of gold nanoparticle-laden microgel using rhodamine 6G (R6G) as analyte molecule. For this,
the microgels are dispersed in aqueous solution of R6G and Raman spectrum is measured. In addition, we
completely dry the microgel and measure the spectrum; drying causes the microgel shrunken.
As shown in Figure 3, Raman intensity in wet micogel is highly improved than surrounding because
gold nanoparticles in microgel enable the strong localization of electromagnetic field on their surface. The
dried microparticles exhibit higher intensity due to improved concentration of gold nanoparticles.
Figure 3: Raman spectra of 0.1 mM rhodamine 6G measured with dried microgel, wet microgel, and surrounding
To show selective exclusion, we disperse microgels in aqueous mixture of R6G and bovine serum
albumin (BSA); BSA has Stokes diameter of approximately 7 nm and is widely used for surface passivation
due to their nonspecific adhesive property. The microgels show Raman intensity comparable with that
measured from microgels dispersed in the aqueous solution of R6G only at the same concentration as shown
in Figure 4, indicating negligible binding of BSA on gold surface. By contrast, gold nanoparticles directly
dispersed in the binary mixture show remarkable reduction of Raman intensity in comparison with that
measured from gold nanoparticles dispersed in the aqueous solution of R6G only. This is because BSA is
adsorbed on the surface of gold, which interrupts access of R6G on the surface.
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Figure 4: Direct detection of small target molecules in protein solution. (a) Schematic of Au NP suspension dispersed in aqueous solution of 1mM rhodamine 6G(R6G) and 1mM bovine serum albumin(BSA). (b)Raman spectra
measured from Au NPs directly dispersed in aqueous solution of 1 mM R6G and 1 mM BSA and aqueous solution of
0.1 mM R6G. (c) Schematic of semipermeable microgels which allow diffusion of small target molecules, while excluding large adhersive proteins. (d)Raman spectra measured from wet microgels dispersed in aqueous solution of
1 mM R6G and 1 mM BSA and aqueous solution of 1 mM R6G.
CONCLUSION
In this work, we produced monodisperse gold nanoparticle-loaded microgels in a microfluidic device.
The microgels provide molecular size cut-off permeation into gel, thereby enabling the selective infusion
of molecules smaller than mesh size. Mesh size are controlled by adjusting precursor concentration. Raman spectra of small target molecules can be directly obtained from mixtures containing large proteins,
while avoiding any interruption of intensity. This microgel platform is applicable for a wide range of invitro and in-vivo detection of bioactive molecules.
ACKNOWLEDGEMENTS
This work was supported by the Fundamental Research Program (PNK 4150) of the Korean Institute
of Materials Science (KIMS) and the Midcareer Researcher Program (2014R1A2A2A01005813) through
the National Research Foundation (NRF) grant funded by the Ministry of Science, ICT and Future Planning (MSIP).
REFERENCES
[1] A. Kim, S. J. Barcelo, R. S. Williams, & Z. Li, “Melamine Sensing in Milk Products by Using Surface Enhanced Raman Scattering,” Anal. Chem., 84, 9303−9309, 2012.
[2] H.Torul, H.Ciftci, F.C.Dudak, Y.Adiguzel, H.Kulah, I.H.Boyaci,&U.Tagmer, “Glucose determination based on a two component self-assembled monolayer functionalized surface-enhanced Raman
spectroscopy (SERS) probe,” Analytical Methods., 6, 5097-5104, 2014.
CONTACT
* Shin-Hyun Kim; phone: +82-42-350-3911; [email protected]
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