Tuning of Hydrogel Architectures by Ionotropic Gelation in Microfluidics: Beyond Batch Processing to Multimodal Diagnostics (original) (raw)
Related papers
Molecules
Poly(ethylene glycol) diacrylate (PEGDA) microgels with tuneable size and porosity find applications as extracellular matrix mimics for tissue-engineering scaffolds, biosensors, and drug carriers. Monodispersed PEGDA microgels were produced by modular droplet microfluidics using the dispersed phase with 49–99 wt% PEGDA, 1 wt% Darocur 2959, and 0–50 wt% water, while the continuous phase was 3.5 wt% silicone-based surfactant dissolved in silicone oil. Pure PEGDA droplets were fully cured within 60 s at the UV light intensity of 75 mW/cm2. The droplets with higher water content required more time for curing. Due to oxygen inhibition, the polymerisation started in the droplet centre and advanced towards the edge, leading to a temporary solid core/liquid shell morphology, confirmed by tracking the Brownian motion of fluorescent latex nanoparticles within a droplet. A volumetric shrinkage during polymerisation was 1–4% for pure PEGDA droplets and 20–32% for the droplets containing 10–40 w...
Scientific Reports, 2022
Droplet microfluidic has been established to synthesize and functionalize micro/nanoparticles for drug delivery and screening, biosensing, cell/tissue engineering, lab-on-a-chip, and organ-on-achip have attracted much attention in chemical and biomedical engineering. Chitosan (CS) has been suggested for different biomedical applications due to its unique characteristics, such as antibacterial bioactivities, immune-enhancing influences, and anticancer bioactivities. The simulation results exhibited an alternative for attaining visions in this complex method. In this regard, the role of the flow rate ratio on the CS droplet features, including the generation rate and droplet size, were thoroughly described. Based on the results, an appropriate protocol was advanced for controlling the CS droplet properties for comparing their properties, such as the rate and size of the CS droplets in the microchip. Also, a level set (LS) laminar two-phase flow system was utilized to study the CS dropletbreaking process in the Flow Focused-based microchip. The outcomes demonstrated that different sizes and geometries of CS droplets could be established via varying the several parameters that validated addressing the different challenges for several purposes like drug delivery (the droplets with smaller sizes), tissue engineering, and cell encapsulation (the droplets with larger sizes), lab-on-achip, organ-on-a-chip, biosensing and bioimaging (the droplets with different sizes). An experimental study was added to confirm the simulation results. A drug delivery application was established to verify the claim. Monodisperse micro/nanoparticles with the same morphology and size have attracted much attention in labon-a-chip 1,2 , aptasensors 3,4 , biosensors 5-7 , drug delivery 8-10 , tissue engineering 10 , catalysis 11 , and electro/optic devices 12. Many attempts have been established to generate uniform micro/nano-particles with on-demand and required morphologies, shapes, and sizes by conventional approaches, including dispersion polymerization 13 , emulsion polymerization 14 , precipitation polymerization 15 , layer-by-layer assemblies 16 , and shirasu porous glass (SPG) membrane emulsification 17. However, the typical emulsion droplet approaches are irrepressible. The generated droplets (particularly the non-spherical) are divergent in shape and size 18. Due to the interfacial tensions between the two phases, the conventional techniques to produce droplets shrink into spheres, making it hard to provide suitable shaped micro/nanoparticles (with high quality) 9,19. Furthermore, typical techniques are costly, inflexible, time-consuming, and complex. Thus, superior approaches are required to generate monodisperse micro/nano-particles with on-demand morphology, shape, and size. Microfluidics and nanofluidics are the sciences and technologies of the systems with integrated channels in micro-scaled and nano-scaled sizes (10 to 100 µm and nm), in which minimal amounts of fluids (generally 1 L to 10 −9 L) may flow in desired fabrication manipulated and controlled systematically 19. Droplet microfluidics has attracted much attention in material fabrication and biomedical devices 20. Droplet microfluidics, including passive hydrodynamic pressure 21 and active external actuation 22 techniques, are promising for generating monodisperse micro/nanoparticles. The critical difference is the external forces required for the active method, including
Scientific Reports, 2020
The combination of different imaging modalities can allow obtaining simultaneously morphological and functional information providing a more accurate diagnosis. This advancement can be reached through the use of multimodal tracers, and nanotechnology-based solutions allow the simultaneous delivery of different diagnostic compounds moving a step towards their safe administration for multimodal imaging acquisition. Among different processes, nanoprecipitation is a consolidate method for the production of nanoparticles and its implementation in microfluidics can further improve the control over final product features accelerating its potential clinical translation. A Hydrodynamic Flow Focusing (HFF) approach is proposed to produce through a ONE-STEP process Multimodal Pegylated crosslinked Hyaluronic Acid NanoParticles (PEG-cHANPs). A monodisperse population of NPs with an average size of 140 nm is produced and Gd-DTPA and ATTO488 compounds are co-encapsulated, simultaneously. The results showed that the obtained multimodal nanoparticle could work as MRI/Optical imaging probe. Furthermore, under the Hydrodenticity effect, a boosting of the T1 values with respect to free Gd-DTPA is preserved. Multimodal Imaging is a promising approach that allows the combination of different imaging techniques, overcoming limitations proper of every single modality 1,2. For example, recently, Magnetic Resonance Imaging (MRI) and Optical imaging (OI) have been used in combination to obtain the excellent sensitivity of the OI with the high spatial resolution of the MRI 3-5. Image acquisition can occur at different times (asynchronously) requiring post-processing analyses performed through digital image manipulation techniques; however, the best consistency both in time and space is achieved when images are simultaneously acquired (synchronously) 6. Despite the great advantages in the Hardware developments, probes able to support simultaneous acquisitions are still missing. Indeed, in current clinical practice, a cocktail of diagnostic compounds is injected with extremely high risk for the patient. In this scenario, the possibility to efficiently co-deliver through a single vector, different diagnostic compounds for different imaging modalities represents a key point. This challenge can be adequately tackled by applying nanotechnologies to the medical field 7-9. Indeed, nanosystems can be used as vectors of active agents and their composition, size, shape, and surface chemistry can be finely modulated to obtain the simultaneous delivery of multiple diagnostic compounds with a significant impact on an early and accurate diagnosis 10-12. Nanovectors can provide simultaneous visualization of the diseased site through different innovative imaging techniques, enhanced-circulation time for the diagnostic compounds, controlled release kinetics, and superior dose scheduling for improved patient compliance 13. However, when systemically injected, nanoparticles are immediately sequestered by macrophages
Chitosan Microgels and Nanoparticles via Electrofluidodynamic Techniques for Biomedical Applications
Gels, 2016
Electrofluidodynamics techniques (EFDTs) are emerging methodologies based on liquid atomization induced by electrical forces to obtain a fine suspension of particles from hundreds of micrometers down to nanometer size. As a function of the characteristic size, these particles are interesting for a wide variety of applications, due to the high scalability of chemical and physical properties in comparison to the bulk form. Here, we propose the optimization of EFDT techniques to design chitosan systems in the form of microgels or nanoparticles for several biomedical applications. Different microscopy techniques (Optical, SEM, TEM) have been used to investigate the morphology of chitosan systems at multiple size scale. The proposed study confirms the high versatility and feasibility of EFDTs for creating micro and nano-sized carriers for cells and drug species.
Single-step design of hydrogel-based microfluidic assays for rapid diagnostics
Lab on a Chip, 2014
For the first time we demonstrate a microfluidic platform for the preparation of biosensing hydrogels by in-situ polymerization of polyethyleneglycol diacrylate (PEG-DA) in a single step. Capillary pressure barriers enable the precise formation of gel microstructures for fast molecule diffusion. Parallel arrangement of these finger structures allows for macroscopic and standard equipment readout methods. The analyte automatically fills the space inbetween the gel fingers by the hydrophilic nature of the gel. Introducing the functional structures in the chip fabrication allows for rapid assay customization by making surface treatment, gel curing mask alignment and washing steps obsolete. Simple handling and functionality are illustrated by assays for matrix metalloproteinase, an important factor in chronic wound healing. Assays for total protein concentration and cell counts are presented, demonstrating the possibilities for a wide range of fast and simple diagnostics.
Novel microgels fabricated on microfluidic devices
4th Micro and Nano Flows Conference (MNF 14), London (UK), 7 - 10 September, 2014
Microgels are micrometer sized particles consisting of a polymer network that show potential for the delivery of both hydrophilic and hydrophobic drugs. Microfluidic devices provide an excellent format for the generation of monodispersed droplets due to the precise manipulation of fluids and flow rates within the microchannels. Microfluidic droplet generation chips were therefore designed using T-junction and flow focusing geometries in glass. For microgel synthesis, monomers, crosslinker and initiator were added to the dispersed phase and water was used as the continuous phase. Controlled formation of monodisperse droplets was achieved with both geometries and droplets were collected off-chip for photopolymerisation. Three types of microgel were formed using this setup: poly(ethylene glycol) diacrylate, poly(propylene glycol) diacrylate, and tetrahydropyran acrylate-ethylene glycol dimethacrylate (THPA-EGDMA) microgels. THPA is a novel material for microgels that can be turned from hydrophobic to amphiphilic by hydrolysation. THPA-EGDMA microgels in particular demonstrated a strong response to pH changes due to the build-up of electrostatic force under high pH, showing potential for the encapsulation and release of drugs.
Microfluidics and hydrogel: A powerful combination
Reactive and Functional Polymers, 2019
Microfluidics is a very useful and promising technology that allowed engineering a huge variety of developments in several fields, such as biology, biomedical engineering, biotechnology, biochemistry, medicine and tissue engineering, among others. Moreover, when microfluidic is combined with hydrogel, the possibilities seem to be limitless. However, it is not found in the bibliography any report that shows the wide range of developments and application fields of this combination. In this review, the bibliography is explored by looking for these new systems that, combining microfluidics and hydrogels, substantially contribute to the state of the art. Seven large application fields are identified-from 649 papers reviewed: 1) cell culture (out of the scope of this review), 2) biosensors, 3) gradient generator microdevices (GGMD), 4) active elements of hydrogel embedded into microfluidic devices, 5) separation devices, 6) models and 7) other uses. Most of these fields are presented and discussed in detail, the great benefits of the combination are highlighted and perspectives on future directions are exposed.
Microscale hydrogels for medicine and biology: synthesis, characteristics and applications
Journal of Mechanics of Materials and Structures, 2007
Microscale hydrogels with dimensions of 200 µm or less are powerful tools for various biomedical applications such as tissue engineering, drug delivery, and biosensors, due to their size, biocompatibility, and their controllable biological, chemical, and mechanical properties. In this review, we provide a broad overview of the approaches used to synthesize and characterize microgels, as well as their applications. We discuss the various methods used to fabricate microgels, such as emulsification, micromolding, microfluidics, and photolithography. Furthermore, we discuss the effects of porosity and crosslinking density on the mechanical and biological properties of hydrogels. In addition, we give specific examples of the use of hydrogels, such as scaffolds and cell encapsulation for tissue engineering, controlled release materials for drug delivery, and environmentally sensitive sensors for microdevices. Finally, we will discuss the future applications of this technology.
Facile fabrication processes for hydrogel-based microfluidic devices made of natural biopolymers
Biomicrofluidics, 2014
We present facile strategies for the fabrication of two types of microfluidic devices made of hydrogels using the natural biopolymers, alginate, and gelatin as substrates. The processes presented include the molding-based preparation of hydrogel plates and their chemical bonding. To prepare calcium-alginate hydrogel microdevices, we suppressed the volume shrinkage of the alginate solution during gelation using propylene glycol alginate in the precursor solution along with sodium alginate. In addition, a chemical bonding method was developed using a polyelectrolyte membrane of poly-L-lysine as the electrostatic glue. To prepare gelatin-based microdevices, we used microbial transglutaminase to bond hydrogel plates chemically and to cross-link and stabilize the hydrogel matrix. As an application, mammalian cells (fibroblasts and vascular endothelial cells) were cultivated on the microchannel surface to form three-dimensional capillary-embedding tissue models for biological research and tissue engineering. V
Microfluidics-based fabrication of cell-laden microgels
Biomicrofluidics, 2020
Microfluidic principles have been extensively utilized as powerful tools to fabricate controlled monodisperse cell-laden hydrogel microdroplets for various biological applications, especially tissue engineering. In this review, we report recent advances in microfluidic-based droplet fabrication and provide our rationale to justify the superiority of microfluidics-based techniques over other microtechnology methods in achieving the encapsulation of cells within hydrogels. The three main components of such a system—hydrogels, cells, and device configurations—are examined thoroughly. First, the characteristics of various types of hydrogels including natural and synthetic types, especially concerning cell encapsulation, are examined. This is followed by the elucidation of the reasoning behind choosing specific cells for encapsulation. Next, in addition to a detailed discussion of their respective droplet formation mechanisms, various device configurations including T-junctions, flow-foc...