Colloids and Surfaces B: Biointerfaces 145 (2016) 21–29
Contents lists available at ScienceDirect
Colloids and Surfaces B: Biointerfaces
j o ur nal ho me pa ge: www.elsevier.com/locate/colsurfb
Functionalized poly(ethylene glycol) diacrylate microgels by
microfluidics: In situ peptide encapsulation for in serum selective
protein detection
Giorgia Celetti
a,d
, Concetta Di Natale
a,b
, Filippo Causa
a,b,c,∗
, Edmondo Battista
c
,
Paolo A. Netti
a,b,c
a
Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia (IIT), Largo Barsanti e Matteucci 53, 80125 Naples, Italy
b
Department of Chemical and Materials Engineering and Industrial Production, University of Naples ‘Federico II’, Piazzale Tecchio 80, 80125 Naples, Italy
c
Interdisciplinary Research Centre on Biomaterials (CRIB), University “Federico II”, Piazzale Tecchio 80, 80125 Naples, Italy
d
Department of Applied Science and Technology, Polytechnic of Turin, Corso Duca degli Abbruzzi, 24, 10129 Turin, Italy
a r t i c l e i n f o
Article history:
Received 8 January 2016
Received in revised form 18 April 2016
Accepted 19 April 2016
Available online 24 April 2016
Keywords:
Droplet-microfluidics
PEGDA-microgels
Peptide
Protein-binding
a b s t r a c t
Polymeric microparticles represent a robustly platform for the detection of clinically relevant analytes
in biological samples; they can be functionalized encapsulating a multiple types of biologics entities,
enhancing their applications as a new class of colloid materials. Microfluidic offers a versatile platform
for the synthesis of monodisperse and engineered microparticles. In this work, we report microfluidic
synthesis of novel polymeric microparticles endowed with specific peptide due to its superior specificity
for target binding in complex media. A peptide sequence was efficiently encapsulated into the polymeric
network and protein binding occurred with high affinity (K
D
0.1–0.4 M). Fluidic dynamics simulation
was performed to optimize the production conditions for monodisperse and stable functionalized micro-
gels. The results demonstrate the easy and fast realization, in a single step, of functionalized monodisperse
microgels using droplet-microfluidic technique, and how the inclusion of the peptide within polymeric
network improve both the affinity and the specificity of protein capture.
© 2016 Elsevier B.V. All rights reserved.
1. Introduction
In the recent years, hydrogels-based technologies has been
widely developed for a range of biotechnology applications includ-
ing diagnostic [1–3], drug delivery [4,5], and tissue engineering
[6,7]. Due to their biocompatible and highly tunable nature
they represent ideal candidates for biosensing applications. Their
microstructure and interfacial proprieties can also be rendered
responsive to various stimuli through chemical and physical cues
resulting in “smart” materials which can respond to their local
environment [1]. In particular, hydrogels can be engineer with
different biological entities such as nucleic acids or peptides for
capture and detection of proteins, DNA, mRNA and microRNA [8].
Hydrogels are typically prepared and processed as bulk materi-
als such as monolithic structures or supported films. However,
∗
Corresponding author at: Department of Chemical and Materials Engineering
and Industrial Production and Interdisciplinary Research Centre on Biomaterials
(CRIB), University “Federico II”, Piazzale Tecchio 80, 80125 Naples, Italy.
E-mail address: causa@unina.it (F. Causa).
emerging applications require miniaturization and tailoring of
hydrogel architecture at increasingly small length scales for deliv-
ery and transport purposes in microscopic environments. This
has spurred the development of various processes for the syn-
thesis of colloidal and microparticle hydrogels, or “microgels” [1].
Hydrogel microparticles have been suggested as diagnostic tools
for the rapid, multiplexed screening of biomolecules due to their
advantages in detection and quantification [9–11]. Compared to
traditional planar arrays, particle-based arrays offer easier probe-
set modification, more efficient mixing steps, and higher degrees
of reproducibility [12]. However appropriate methods for achiev-
ing the functionalization of large microparticles have not yet been
developed [13].
Among the various approaches for synthesizing hydrogel
microparticles, microfluidics represent one of the most promis-
ing methods for the production and the functionalization of
monodisperse microgels, including droplet microfluidics [14–16]
and flow lithography [14]. In particular, droplet microfluidics facil-
itates fabrication of spherical microparticles (i.e., microspheres) or
microparticles with complex chemical compositions, and poten-
tially enables higher throughput synthesis [17]. Prior reports have
http://dx.doi.org/10.1016/j.colsurfb.2016.04.036
0927-7765/© 2016 Elsevier B.V. All rights reserved.