Isabelle Kraus

Polyacrylamid/silver composite particles produced via microfluidic photopolymerization for single particle-based SERS microsensorics.

A micro-continuous-flow process was applied for the preparation of swellable polyacrylamide particles incorporating silver nanoparticles. These sensor particles are formed from a mixture of a colloidal solution of silver nanoparticles and monomer by a droplet-based procedure with in situ photoinitiation of polymerization and a subsequent silver enforcement in batch. The obtained polymer composite particles show a strong SERS effect. Characteristic Raman signals of aqueous solutions of adenine could be detected down to 0.1 μM by the use of single sensor particles. The chosen example demonstrates that the composite particles are suitable for quantitative microanalytical procedures with a high dynamic range (3 orders of magnitude for adenine).

Microfluidic conceived drug loaded Janus particles in side-by-side capillaries device

A side-by-side capillaries microfluidic device was developed to fabricate drug loaded poly(acrylamide)/poly(methyl acrylate) Janus particles in the range of 59-240 μm by UV-assisted free radical polymerization. This system was characterized in terms of continuous and dispersed phases flow rates (Qc/Qd), monomer composition of the two compartments, surfactant nature and concentration, outlet tube diameter and UV intensity. These factors were adequately controlled to get different particle shapes ranging from core-shell to bi-compartmental particles. For the latter, a low surfactant concentration (0.75 wt.%) was necessary when the two dispersed phases were pumped at equal flow rate, while at high surfactant concentration, dispersed phases flow rates have to be changed. FTIR analysis suggested complete polymerization of monomers and cytotoxicity test showed these particles were biocompatible having LD 50 of 9 mg/mL. Both ketoprofen and sodium fluorescein were released in sustained release manner at pH 6.8 by following a diffusion type release mechanism. Drug release was faster for bigger particles and found to result from the irregular distribution of the two phases and indentation on bigger particles as revealed by SEM analysis. In comparison, sodium fluorescein release was slower which was attributed to low encapsulation but could be modified by decreasing crosslinker concentration.

Multiscale materials from microcontinuous-flow synthesis: ZnO and Au nanoparticle-filled uniform and homogeneous polymer microbeads

Tri(propylene glycol) diacrylate (TPGDA) was found to be an excellent monomer for the stabilization and dispersion of inorganic nanoparticles. Uniform nano-Au/poly(TPGDA) and nano-ZnO/poly(TPGDA) composite microbeads were synthesized in situ using a designed axisymmetric capillary-based flow-focusing microfluidic device without any additional surfactant or coupling agent. Using the designed mixing-enhanced microfluidic device, homogeneous nano-inorganic/polymer composites with a high content of nanoparticles were obtained. Morphologies of the composites were characterized by SEM, TEM, surface microscopy, dark-field microscopy and internal fluorescence.

Engineering Polymer Microparticles by Droplet Microfluidics

Capillary-based flow-focusing and co-flow microsystems were developed to produce sphere-like polymer micro-particles of adjustable sizes in the range of 50 to 600 μm with a narrow size distribution (CV < 5%) and different morphologies (core–shell, janus, and capsules). Rod-like particles whose length was conveniently adjusted between 400 μm and few millimeters were also produced using the same microsystems. Influence of operating conditions (flow rate of the different fluid, microsystem characteristic dimensions, and design) as well as material parameters (viscosity of the different fluids and surface tension) was investigated. Empirical relationships were thus derived from experimental data to predict the microparticle’s overall size, shell thickness, or rods length. Besides morphology, microparticles with various compositions were synthesized and their potential applications highlighted: drug-loaded microparticles for new drug delivery strategies, composed inorganic–organic multiscale microparticles for sensorics, and liquid crystalline elastomer microparticles showing an anisotropic reversible shape change upon temperature for thermal actuators or artificial muscles.

Microfluidic conceived Trojan microcarriers for oral delivery of nanoparticles.

In this study, we report on a novel method for the synthesis of poly(acrylamide) Trojan microparticles containing ketoprofen loaded poly(ethyl acrylate) or poly(methyl acrylate) nanoparticles. To develop these composite particles, a polymerizable nanoemulsion was used as a template. This nanoemulsion was obtained in an elongational-flow micromixer (μRMX) which was linked to a capillary-based microfluidic device for its emulsification into micron range droplets. Downstream, the microdroplets were hardened into Trojan particles in the size range of 213-308 μm by UV initiated free radical polymerization. The nanoemulsion size varied from 98 -132 nm upon changes in surfactant concentration and number of operating cycles in μRMX. SEM and confocal microscopy confirmed the Trojan morphology. Under SEM it was observed that the polymerization reduced the size of the nanoemulsion down to 20-32 nm for poly(ethyl acrylate) and 10-15 nm for poly(methyl acrylate) nanoparticles. This shrinkage was confirmed by cryo-TEM studies. We further showed that Trojan microparticles released embedded nanoparticles on contact with suitable media as confirmed by transmission electron microscopy. In a USP phosphate buffer solution of pH 6.8, Trojan microparticles containing poly(ethyl acrylate) nanoparticles released 35% of encapsulated ketoprofen over 24h. The low release of the drug was attributed to the overall low concentration of nanoparticles and attachment of some of nanoparticles to the poly(acrylamide) matrix. Thus, this novel method has shown possibility to develop Trojan particles convieniently with potential to deliver nanoparticles in the gastrointestinal tract.

Continuous-Microflow Synthesis and Morphological Characterization of Multiscale Composite Materials Based on Polymer Microparticles and Inorganic Nanoparticles

This paper presents a new route to the synthesis of uniform and size-controlled inorganic/organic composite microparticles by means of microreaction technology. Au-nanoparticles in the range of 3 to 14 nm are synthesized by reduction of tetrachloroauric acid, while ZnO-nanoparticles (200–2000 nm) are synthesized in a continuous-flow twostep process using microtube arrangements for microsegmented flow. Both inorganic nanoparticles have a wellcontrolled size and narrow size distribution. Upon surface modification, the nanoparticles are then mixed on one hand with an acrylate-based monomer and, on the other hand, with an aqueous solution of acrylamide. Both solutions were then emulsified into uniform core-shell droplets by means of a capillary-based microfluidic device. Droplet’s shell was hardened through UV-induced polymerization, whereas the core led to a hydrogel upon thermal-induced polymerization. Core-shell polymer microparticles (200–300 μm) with inorganic nanoparticles selectively incorporated into the core and the shell are thus obtained as proven by extensive morphological characterizations using electronic and optical microscopies.