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Synthetic Microfluidic Paper : high surface and high porosity polymer micropillar arrays
Abstract
We introduce Synthetic Microfluidic Paper, a novel porous material for microfluidic applications that consists of an OSTE polymer that is photostructured in a well-controlled geometry of slanted and interlocked micropillars. We demonstrate the distinct benefits of Synthetic Microfluidic Paper over other porous microfluidic materials, such as nitrocellulose, traditional paper and straight micropillar arrays: in contrast to straight micropillar arrays, the geometry of Synthetic Microfluidic Paper was miniaturized without suffering capillary collapse during manufacturing and fluidic operation, resulting in a six-fold increased internal surface area and a three-fold increased porous fraction. Compared to commercial nitrocellulose materials for capillary assays, Synthetic Microfluidic Paper shows a wider range of capillary pumping speed and four times lower device-to-device variation. Compared to the surfaces of the other porous microfluidic materials that are modified by adsorption, Synthetic Microfluidic Paper contains free thiol groups and has been shown to be suitable for covalent surface chemistry, demonstrated here for increasing the material hydrophilicity. These results illustrate the potential of Synthetic Microfluidic Paper as a porous microfluidic material with improved performance characteristics, especially for bioassay applications such as diagnostic tests.
... High aspect ratio (HAR) micropillars are slender microstructures whose heights (vertical lengths) are considerably higher than their other dimensions, giving rise to their high surface area to volume ratio. The micro texturing of surfaces using high-aspect-ratio (HAR) micropillars enables their applications in dry adhesives [7], elastomeric smart windows [8], micro contact printing [9,10], microfluidics [11][12][13], actuators [14], airflow sensors [15], contact sensors [16], and anti-wetting surfaces [17,18]. However, an increase in their aspect ratio makes them susceptible to deformation under capillary forces, limiting their practical applications [19,20]. ...
... In order to determine how the elastic module of micropillars affects their stability, deflection vs. elastic modulus (E) for various force distributions was plotted ( Figure 4a). As expected, the graph's trend is consistent with the previously collected experimental data [11,25]. Deflection values decreased exponentially with increasing elastic modulus, meaning that higher values of elastic modulus yield less deflection. ...
... In order to determine how the elastic module of micropillars affects their stability, deflection vs. elastic modulus ( ) for various force distributions was plotted ( Figure 4a). As expected, the graph's trend is consistent with the previously collected experimental data [11,25]. Deflection values decreased exponentially with increasing elastic modulus, meaning that higher values of elastic modulus yield less deflection. ...
High-aspect-ratio (HAR) micropillar arrays offer a wide range of applications in micro-contact printing, switchable transparent optical windows, superhydrophobic surfaces, mechanical sensors, and actuators, due to their properties such as large surface area and excellent mechanical compliance. However, owing to their high aspect ratio, these microstructures are prone to lateral deflection by elastocapillary forces in liquid environments, which is known as top-gathering, limiting their manufacturing processes and applications. Here, the impact of symmetry on evaporation triggered top-gathering of micropillars was studied numerically. The initiation of the micropillar deflection due to capillary forces under varying force distributions was simulated using a COMSOL Multiphysics simulation package. The simulation was carried out for the configurations of two, four, and an array of micropillars. For the four micropillar configuration, a new equation was suggested for calculating the micropillar deflection due to elastocapillary forces, using force distributions around the micropillars. The suggested equation was verified by comparison with the experimental observations. The effect of droplet evaporation on deflection/top-gathering of micropillars was also investigated. It was found that initiation of deflection is due to asymmetry at the rim of the droplet, generating domino-like deflection of the other micropillars. This study provides a new equation/criterion for estimating deflection of the micropillars, suggesting array designs that are resistant to such deflections when interacting with liquids.
... Another promising application of SPPW-printed microstructures is the field of microfluidic generation and droplet manipulation, which may be useful for medical diagnostic assays, biosensing surfaces, and cell culture 123,124 . Hansson et al. demonstrated a platform for the fabrication of synthetic microfluidic paper with well-controlled arrays of interlocked micropillars, formed by SPPW through a photomask 124 . ...
... These results illustrate the potential of synthetic microfluidic structures as high area/volume biosensing surfaces, providing improved performance compared to conventional porous microfluidic materials. Yasuga and colleagues reported emergent 3D fluid lattices by the occurrence of fluid trap geometries in every lattice unit cell of SPPW-printed interconnected solid scaffolds, which can be used for self-digitization, generation, transport, and merging of microdroplets inside 3D architectures 123 . A 3D solid scaffold produced using SPPW was filled with two immiscible fluids, which spontaneously self-organized as discrete fluidic particles (in blue) in a continuous phase to yield a 3D tri-material periodic structure (Fig. 10c, left). ...
... b Artificial axons printed through (DLPbased) SPPW printing 13 . c 3D fluidic particle arrays inside polymer micropillar scaffolds (Left) and bright field images (Middle) and confocal images (Left) of a core-shell microcapsule that contains yeast cells 123 Fig. 11 a, b One-step artificial axon fabrication through hybrid SPPW using digital and physical photomasks 122 ; a Artificial axons fabricated by self-propagated photopolymerization, facilitated by digital mask projection. Estimated range of Young 's elastic modulus E span four orders of magnitude (0.1 -100 kPa). ...
Photocrosslinkable polymers have been exploited to attain impressive advantages in printing freestanding, micrometer-scale, mechanically compliant features. However, a more integrated understanding of both the polymer photochemistry and the microfabrication processes could enable new strategic design avenues, unlocking far-reaching applications of the light-based modality of additive manufacturing. One promising approach for achieving high-aspect-ratio structures is to leverage the phenomenon of light self-trapping during the photopolymerization process. In this review, we discuss the design of materials that facilitate this optical behavior, the computational modeling and practical processing considerations to achieve high aspect-ratio structures, and the range of applications that can benefit from architectures fabricated using light self-trapping—especially those demanding free-standing structures and materials of stiffnesses relevant in biological applications. Coupled interactions exist among material attributes, including polymer composition, and processing parameters such as light intensity. We identify strong opportunities for predictive design of both the material and the process. Overall, this perspective describes the wide range of existing polymers and additive manufacturing approaches, and highlights various future directions to enable constructs with new complexities and functionalities through the development of next-generation photocrosslinkable materials and micromanufacturing methods.
... We fabricated periodic micropillar scaffolds with a primitive tetragonal lattice using multidirectional lithography of off-stoichiometric thiol-ene (OSTE; for details see ref. 19 FLUID3EAMS spontaneously forms structures with 3D microscale periodicity in three structural elements: a continuous microscaffold solid (grey), dispersed fluid particles of a primary fluid (blue) and a continuous secondary fluid that fills the remaining void (orange or colourless). Magenta indicates the interface between two fluids. ...
... Three-dimensional micropillar array fabrication. We define scaffold geometries S and S′ as follows: S scaffolds are the primitive tetragonal lattice scaffolds 19 (Extended Data Fig. 1) and S′ scaffolds are the body-centred tetragonal lattice scaffolds 20 . Using a previously reported method 19 , we formed 3D micropillar scaffolds S and S′ in OSTE by quadridirectional photostructuring through a film photomask (JD Photo-Tools and Tokyo Process Service; Supplementary Fig. 1). ...
... We define scaffold geometries S and S′ as follows: S scaffolds are the primitive tetragonal lattice scaffolds 19 (Extended Data Fig. 1) and S′ scaffolds are the body-centred tetragonal lattice scaffolds 20 . Using a previously reported method 19 , we formed 3D micropillar scaffolds S and S′ in OSTE by quadridirectional photostructuring through a film photomask (JD Photo-Tools and Tokyo Process Service; Supplementary Fig. 1). In addition, we fabricated scaffold S using a commercially available 3D printer (Micro, MicroSLA). ...
Structures that are periodic on a microscale in three dimensions are abundant in nature, for example, in the cellular arrays that make up living tissue. Such structures can also be engineered, appearing in smart materials1,2,3,4, photonic crystals⁵, chemical reactors⁶, and medical⁷ and biomimetic⁸ technologies. Here we report that fluid–fluid interfacial energy drives three-dimensional (3D) structure emergence in a micropillar scaffold. This finding offers a rapid and scalable way of transforming a simple pillar scaffold into an intricate 3D structure that is periodic on a microscale, comprising a solid microscaffold, a dispersed fluid and a continuous fluid. Structures generated with this technique exhibit a set of unique features, including a stationary internal liquid–liquid interface. Using this approach, we create structures with an internal liquid surface in a regime of interest for liquid–liquid catalysis. We also synthesize soft composites in solid, liquid and gas combinations that have previously not been shown, including actuator materials with temperature-tunable microscale pores. We further demonstrate the potential of this method for constructing 3D materials that mimic tissue with an unprecedented level of control, and for microencapsulating human cells at densities that address an unresolved challenge in cell therapy.
... However, the cotton fibers that compose the filter papers are randomly intertwined, which may lead to volume variation. Microfabrication can offer structures composed of regular micro-patterns, such as micropillar arrays [17], microchannels [18], and synthetic microfluidic paper (SMP) [19], which are potential in the use for precise sampling. In particular, the SMP which is three-dimensional, regularly ordered microstructures of a photosensitive polymer pumps and maintains liquid volumes with excellent accuracy and repeatability. ...
... Filter paper used for sampling was Whatman No. 4 (GE Healthcare Japan, Japan). The sampling strip was based on SMP [19]. The SMP was made of off-stoichiometry thiolene (OSTE, OSTEMER 220 Litho, Mercene Labs AB, Sweden). ...
... The thiol-ene reaction triggered by UV exposure induces covalent bonds between the two monomers, resulting in a transparent OSTE polymer [24]. The OSTE contains unreacted thiol groups on the polymer surfaces, which allows surface modification based on polymer-chain grafting [19]. ...
Non-invasive diagnosis on biological liquid samples, such as urine, sweat, saliva, and tears, may allow patients to evaluate their health by themselves. To obtain accurate diagnostic results, target liquid must be precisely sampled. Conventionally, urine sampling using filter paper can be given as an example sampling, but differences in the paper structure can cause variations in sampling volume. This paper describes precise liquid sampling using synthetic microfluidic papers, which are composed of obliquely combined micropillars. Sampling volume accuracy was investigated using different designs and collection methods to determine the optimal design and sample collecting method. The optimized protocol was followed to accurately measure potassium concentration using synthetic microfluidic paper and a commercially available densitometer, which verified the usefulness of the synthetic microfluidic papers for precision sampling.
... Capillarity is a useful phenomenon for microfluidics because the capillary flow of a liquid functions as a pressure source for microfluidic devices, resulting in a pumpless microfluidic system, which can be referred to as capillary or open microfluidics [19][20][21]. One typical phenomenon of capillary flow is that a narrow glass capillary draws water as soon as the capillary comes into contact with liquid water. ...
... The OSTE polymer surface, including thiol groups, can be modified by rapid photografting onto hydrophilic/hydrophobic surfaces [43] or protein-immobilized surfaces [44]. Hansson et al. fabricated a micropillar scaffold based on OSTE for the first time, which was called "synthetic (microfluidic) paper" [19]. Fig. 5(b) shows the synthetic paper composed of slanted and mutually interconnected straight micropillars. ...
Herein, I review our recent work toward developing methods for generating three-dimensional (3D) droplet arrays driven by capillarity. Microdroplet array-based systems are useful for bioassays and bioengineering because they require only small amounts of samples and reagents and provide the high throughput. Various methods have been developed for preparing droplet arrays, among which methods based on capillarity have attracted considerable attention owing to their simplicity. I and collaborators have developed such methods based on capillary flow, including a method for preparing droplet arrays via oil–water replacement. We recently proposed our own concept of “fluid–fluid interfacial energy driven 3D structure emergence in a micropillar scaffold (FLUID3EAMS)” and its application. FLUID3EAMS allows a 3D droplet (or hydrogel bead) array to be generated in a micropillar scaffold by passing a fluid–fluid interface through the scaffold. This approach is useful for applications requiring ordered or arrayed microdroplets in biosensors, biophysics, biology, and tissue engineering. This review is an extended version of the article “FLUID3EAMS: Fluid–Fluid Interfacial Energy Driven 3D Structure Emergence in a Micropillar Scaffold and Development in Bioengineering” published in Seibutsu Butsuri (vol. 62, p. 110–113, 2022).
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... In Paper I, 'fluid-fluid interfacial energy driven 3D structure emergence in a micropillar scaffold' (FLUID3EAMS) is demonstrated as a novel microfluidic compartmentalization method [80]. First, micropillar scaffolds are fabricated with a tetragonal lattice, using the multidi-12 CHAPTER 3. NEW TOOLS FOR MICROFLUIDIC COMPARTMENTALIZATION rectional photolitography of off-stochiometric thiol-ene (OSTE), previously reported [81]. Thereafter, the scaffolds are sequentially filled with two immiscible fluids in a direction along the lattice symmetry axis. ...
... Another potent tool used for smart material fabrication is additive and subtractive manufacturing. 3D printing [96,97], multilayer assembly [98], multidirectional photolithography [81,99], micromachining [100], and laser patterning [101,102] are examples of different additive and subtractive manufacturing techniques commonly used in smart material or structure synthesis. Methods such as 3D printing, micromachining, and laser patterning have a trade-off between their volumetric manufacturing rate and spatial resolution. ...
The organisation of fluids in small compartments is ubiquitous in nature, such as in the cellular composition of all life. This work explores several engineering avenues where microscale fluid compartmentalization can bring novel material properties or novel functionality in life sciences or medicine.
Here, we introduce four unique compartmentalization methods: 1) 3D fluid self-organisation in microscaffolds (FLUID3EAMS), 2) 2D microcapillary arrays on a dipstick (Digital Dipstick), 3) a sliding microfluidic platform with cross-flow (Slip-X-Chip), and 4) compartmentalization by cutting of soft solid matter (Solidify & Cut). These methods were used in a wide range of applications.
Within the area of smart materials, we applied FLUID3EAMS to synthesize materials with temperature-tuneable permeability and surface energy and to establish, in a well-controlled fashion, tissue-like materials in the form of 3D droplet interface bilayer networks. Solidify & Cut was used to form soft composites with a new type of magnetic behaviour, rotation-induced ferromagnetism, that allows easy reprogramming of the magnetization of magnetopolymers.
Within the area of medical diagnostics, we applied Digital Dipstick to perform rapid digital bacterial culture in a dipstick format and obtained clinically relevant diagnostic results on samples from patients with a urinary tract infection. Furthermore, Slip-X-Chip enables particle concentration and washing as new functions in sliding microfluidic platforms, which significantly expands their potential application area.
Finally, within the area of cell therapy, we explored the microencapsulation of high concentrations of therapeutic cells and presented a novel technique to fabricate core-shell microcapsules by exploiting the superior material properties of spider silk membranes.
... Here, we investigate "synthetic paper" (Hansson et al., 2016), a micropillar scaffold made of off-stoichiometric thiol-ene (OSTE) (Carlborg et al., 2011), as a substrate for fluorescence-based sensors. The porosity of synthetic paper is lithographically defined and therefore very well controlled. ...
... Here, we introduce "synthetic paper" (Hansson et al., 2016), made of off-stoichiometric thiol-ene (OSTE) (Carlborg et al., 2011), as a substrate for fluorescence-based sensors. The porosity of synthetic paper is lithographically defined and therefore very well controlled. ...
The fluorescence-based detection of biological complexes on solid substrates is widely used in microarrays and lateral flow tests. Here, we investigate thiol-ene micropillar scaffold sheets (“synthetic paper”) as the solid substrate in such assays. Compared to state-of-the-art glass and nitrocellulose substrates, assays on synthetic paper provide a stronger fluorescence signal, similar or better reproducibility, lower limit of detection (LOD), and the possibility of working with lower immunoreagent concentrations. Using synthetic paper, we detected the antibiotic enrofloxacin in whole milk with a LOD of 1.64 nM, which is on par or better than the values obtained with other common tests, and much lower than the maximum level allowed by European Union regulations. The significance of these results lays in that they indicate that synthetically-derived microstructured substrate materials have the potential to improve the performance of diagnostic assays.
... Synthetic paper is a porous synthetic substrate with a low internal surface area designed for use in capillary-driven lateral flow tests. 18 Mercene Labs AB, the company that commercializes synthetic paper, estimates a unit production cost of synthetic paper being 2−4 times that of conventional blood filter paper (personal communication). Besides the uncomplicated and potentially low-cost fabrication of synthetic paper, our choice for this substrate material is motivated by its photolitographically controlled geometry and that the material can be fabricated as a porous sheet, which could potentially allow for easy integration by layering, a method commonly employed in lateral flow test fabrication. ...
... We fabricated plasma extractors from synthetic paper using multidirectional photostructuring in off-stoichiometric thiol− ene (OSTE) in a process previously reported. 18 The extractors consist of a square sample loading pad (side length 16.8 mm, thickness t = 300 μm) that is connected to a rectangular plasma channel (width 2 mm, length 30 mm, thickness t = 100 μm) (Figure 1). The micropillars had a circular cross-section with diameter d = 50 μm and interspacing p = 100 μm. ...
The separation of plasma from whole blood is the first step in many diagnostic tests. Point-of-care tests often rely on integrated plasma filters, but protein retention in such filters limits their performance. Here, we investigate plasma separation on interlocked micropillar scaffolds ("synthetic paper") by the local agglutination of blood cells coupled with the capillary separation of the plasma. We separated clinically relevant volumes of plasma with high efficiency in a separation time on par with that of state of the art techniques. We investigated different covalent and non-covalent surface treatments (PEGMA, HEMA, BSA, O2 plasma) on our blood filter and their effect on protein recovery, and identified O2 plasma treatment and 7.9 μg/cm² agglutination antibody as most suitable treatments. Using these treatments, we recovered at least 82% of the blood plasma proteins, more than with state-of-the-art filters. The simplicity of our device and the performance of our approach could enable better point-of-care tests.
... 12 However, irregular porous structures at the micron scale lead to scattering and nonuniform distribution of nanoparticles on its surface, thus, affecting optical signal detection. 13,14 Therefore, a paper with a micropillar scaffold has been synthesized from off-stoichiometry-thiol-ene (OSTE) by lithography to prepare ordered microstructures, improving the detection performance. 15 Compared with state-of-the-art glass and nitrocellulose substrates, the synthetic paper exhibits a stronger fluorescence and lower limit of detection (LOD) in detecting enrofloxacin in milk. ...
Blood biomarker detection can conveniently and non-invasively realize early diagnosis in asymptomatic people with Alzheimer's disease (AD). However, disease biomarkers have extremely low abundance; therefore, ultrahigh sensitive detection techniques are required, which are still a challenge. This research proposes a nanostructured lateral flow immunoassay strip combined with Au@SiO2 surface-enhanced Raman scattering (SERS) nanotags (nanostructured SERS-LFIA) for rapid and low-cost detection and to improve the sensitivity, replacing the conventional test line (T line) with inverse opal nitrocellulose. The nanostructured SERS-LFIA is used to detect AD biomarkers as a possible application in early diagnosis. Two AD biomarkers, Aβ42 and Aβ40, encoded by SERS nanotags are simultaneously detected on the same nanostructured T line, with a limit of detection (LOD) of 15.3 and 16.8 fg mL⁻¹, respectively, about 10 times lower than that of SERS-LFIA. The nanostructured SERS-LFIA has great potential in the non-invasive detection of AD biomarkers and early diagnosis.
... To address these challenges, there has been a recent trend in using synthetic microfluidic paper composed of polymers. This innovative material offers several advantages over traditional paper, including improved consistency, more favorable surface chemistry, predictable pore size, and greater control over physical properties (Hansson et al., 2016;Zhou et al., 2021). ...
Microfluidics is an interdisciplinary field that encompasses both science and engineering, which aims to design and fabricate devices capable of manipulating extremely low volumes of fluids on a microscale level. The central objective of microfluidics is to provide high precision and accuracy while using minimal reagents and equipment. The benefits of this approach include greater control over experimental conditions, faster analysis, and improved experimental reproducibility. Microfluidic devices, also known as labs-on-a-chip (LOCs), have emerged as potential instruments for optimizing operations and decreasing costs in various of industries, including pharmaceutical, medical, food, and cosmetics. However, the high price of conventional prototypes for LOCs devices, generated in clean room facilities, has increased the demand for inexpensive alternatives. Polymers, paper, and hydrogels are some of the materials that can be utilized to create the inexpensive microfluidic devices covered in this article. In addition, we highlighted different manufacturing techniques, such as soft lithography, laser plotting, and 3D printing, that are suitable for creating LOCs. The selection of materials and fabrication techniques will depend on the specific requirements and applications of each individual LOC. This article aims to provide a comprehensive overview of the numerous alternatives for the development of low-cost LOCs to service industries such as pharmaceuticals, chemicals, food, and biomedicine.
... Purple food dye is from Lianyungang Xinai Food Technology Company (Lianyungang, China). OSTE is prepared according to a previous report [12]. ...
Microneedles have been used in various applications in biomedical engineering, including drug delivery, biosensing and vaccine delivery. Here, we develop a novel protocol to fabricate silk fibroin/off-stoichiometry thiol-ene (OSTE) microneedle patches. Silk fibroin, as a natural biomaterial, has been proved to be suitable as a drug carrier. At first, silk fibroin solution with drug (insulin in this work) is deposited on a microneedle mold and fully dried. Needle tips made by silk fibroin are formed on the base made by photocurable polymer OSTE using replica molding. The length of needle tips can be adjusted by modifying the concentration of silk fibroin. Such composite structures can make sure the whole silk tip penetrate and dissolve in the skin, with the potential to increase the delivery efficiency.
... In order to achieve the capillary driven flow, the modified surfaces are desired to be superhydrophilic, on which the contact angle of a water droplet is less than 5 • [18]. Integrated micropillar arrays via photolithography can introduce the superhydrophilic surface because the fabricated micropillar arrays increased the surface area and porosity [19,20]. Alternatively, ultrafast laser ablation under ambient environment is proven to be useful in surface modification [21]. ...
Developing a surface modification technique that can be applied to a variety of thermoplastic polymers is of great practical importance. Laser surface treatment is one of effective ways to modify the surface property that can be used for various biomedical applications. In this research, we employed a controllable laser ablation technique on a polymethylmethacrylate (PMMA) surface that can improve the surface wetting property. The ablated hierarchical micro- and nano-structures and surfactant coating of dioctyl sulfosuccinate sodium salt induced controllable capillary driven flows. Morphology and wetting properties of laser ablated PMMA surface have been investigated from the perspective of possible applications in lateral flow assay. We also carried out an experimental investigation on controlling the flow rate and dynamics of capillary driven flow influenced by the ablated surface, channel width, aspect ratio, laser pulse step size, and viscosity of test fluids. While the capillary driven flow was found to follow the modified Lucas-Washburn dynamics, we also observed that the distance of advancing front contact line scaled by the hydraulic radius was inversely proportional to capillary number.
... After we prepared the PMMA mold, we poured PDMS on the PMMA and cured PDMS. After that, we removed the PDMS negative from the PMMA mold and used it as a mold to make an OSTE replica [34], of which the details can be found in Appendix A.1. The curing of the polymer was performed by flood ultraviolet (UV) irradiation (UV radiation lamp, Asiga, Australia). ...
Plasma separation is of high interest for lateral flow tests using whole blood as sample liquids. Here, we built a passive microfluidic device for plasma separation with high performance. This device was made by blood filtration membrane and off-stoichiometry thiol–ene (OSTE) pillar forest. OSTE pillar forest was fabricated by double replica moldings of a laser-cut polymethylmethacrylate (PMMA) mold, which has a uniform microstructure. This device utilized a filtration membrane to separate plasma from whole blood samples and used hydrophilic OSTE pillar forest as the capillary pump to propel the plasma. The device can be used to separate blood plasma with high purity for later use in lateral flow tests. The device can process 45 μL of whole blood in 72 s and achieves a plasma separation yield as high as 60.0%. The protein recovery rate of separated plasma is 85.5%, which is on par with state-of-the-art technologies. This device can be further developed into lateral flow tests for biomarker detection in whole blood.
... In addition, nitrocellulose has strong autofluorescence, and thereafter big signal to noise ratio when applying fluorescent assays on it. Synthetic paper is a novel lateral flow test substrate, fabricated by multi-directional lithography of OSTE [21][22][23]. Synthetic paper is transparent, and has low autofluorescence and uniform microstructure. In addition, there are free thiol groups on the surface of synthetic paper, which can facilitate efficient bonding of immunoreagents. ...
Controlling capillary flow rate of sample liquid is of high interest for lateral flow tests, since the flow rate can affect the dissolution and mixing of the immunoreagents and the efficiency of immunoreactions. Here we develop a facile method to adjust the capillary flow rate on lateral flow test substrates by using tape to cover the surface of substrates. We test this method on the traditional lateral flow test substrate—nitrocellulose and a novel lateral flow test substrate—synthetic paper, which is a porous media made by interlocked off-stoichiometry thiol-ene (OSTE) micropillars. We found that after the surface was covered by tape, the average flow rate decreased to 61% of the original flow rate on nitrocellulose, while the average flow rate increased to at least 320% of the original flow rate on synthetic paper. More interesting, besides the increase of flow rate, the volume capacity of synthetic paper also increases after covered by tape. Furthermore, we investigated the influence of length and position of tape on the capillary flow rate for nitrocellulose. A longer tape will lead to a smaller flow rate. The influence of tape of same length on the flow rate is bigger when the tape is placed closer to the loading pad. These results can help in the flow rate control on lateral flow test substrates, and potentially improve the performance of lateral flow tests.
... In addition to silicon and glass, poly(methyl methacrylate) (PMMA) and polystyrene (PS) were among the first materials to be utilized for microfluidics; albeit, polymers only gained popularity following the introduction of the elastomeric material poly(dimethylsiloxane) (PDMS). George Whitesides and his group at Harvard pioneered the concept of replica molding PDMS [107,108], by pouring the liquid PDMS monomers over structured silicon wafers and curing the polymer to be used as microfluidic devices. Hot embossing for PMMA structuring was also introduced in the 1990s [109], though a silicon master mold was still utilized for this purpose. ...
Despite the recent advancements in the field of microfluidics, the potential of rapid development is often limited due to the inherent challenges posed by the materials used for microfluidic device fabrication. For drug delivery applications, there is a need to identify an optimal material that is cost-effective, compatible with ‘soft-lithography,’ easily replica molded, and resistant to harsh solvents. The family of thiol-ene polymers hold promise as an inexpensive and easy-to-produce alternative. This material shows good chemical compatibility with most organic solvents but falls short for chlorinated solvents which are often used for pharmaceutical applications. Thus, the research presented in this thesis aimed to develop a solvent compatible thiol-ene platform for rapid and cost-effective fabrication of microfluidic chips with a focus on drug delivery applications. This work initially shows the rendering of thiol-ene polymers chloroform compatible in order to open new prototyping avenues for drug delivery purposes. The approach is simple and effective, resulting in a 50-fold increase in chloroform compatibility, allowing for the operation of microfluidic chips in chloroform for several days without any discernible deformation. Next, this thesis shows the novel preparation of small (1-2 μm), monodispersed polylactic acid (PLA) microspheres, utilizing chlorinated solvents for their synthesis. This work presents a simple microfluidic chip design achievable in all microfluidic fabrication labs and relies on flow manipulations to shear of droplets well under the often-regarded minimum size limits. The prepared particles show high monodispersity and significant loading with magnetite nanoparticles; hence, hold promise for magnetically targeted drug delivery. In addition to droplet production, thiol-enes are suited for the bulk precipitation of uniform nanoparticles. The final work presented here focuses on siRNA loading within the lipid-polymer hybrid nanoparticles. This work shows exquisite size control, ranging from 70-300 nm, uniform sizes, and high siRNA encapsulation efficiency. The results obtained during this study presents a facile method to produce cost-effective and solvent compatible thiol-ene microfluidic chips highly suitable for numerous applications. With extensive experimental evidence, the fabricated thiol-ene microfluidic chips are shown to be very efficient for the production of pharmaceutical delivery vehicles of all sizes, ranging from the nano- to the micro-scale.
... 41 Nanoimprinting of thiol-ene has been reported, 42,43 but limited stiffness has resulted in the collapse of HAR micropillars. 44 In contrast, off-stoichiometric thiol−ene-epoxy (OSTE+) 45 features a dual UV/thermal polymerization system that offers robust mechanical properties and durability, a prolonged delay in gelation, the capability of layer bonding, 46 and direct biofunctionalization. 47 The low level of homopolymerization and nearly full reagent conversion during the second curing step lead to a fully polymerized material with no or little leaching, suited for cell applications. 48 Here, we investigate the OSTE+ system for UV nanoimprint lithography and specifically for the structuring of HAR and multilayer nanotopographies. ...
High-aspect-ratio and hierarchically nanostructured
surfaces are common in nature. Synthetic variants are of interest for
their specific chemical, mechanic, electric, photonic, or biologic
properties but are cumbersome in fabrication or suffer from structural
collapse. Here, we replicated and directly biofunctionalized robust,
large-area, and high-aspect-ratio nanostructures by nanoimprint
lithography of an off-stoichiometric thiol−ene-epoxy polymer. We
structured in a single-step process dense arrays of pillars with a
diameter as low as 100 nm and an aspect ratio of 7.2; holes with a
diameter of 70 nm and an aspect ratio of >20; and complex
hierarchically layered structures, all with minimal collapse and
defectivity. We show that the nanopillar arrays alter mechanosensing
of human hepatic cells and provide precise spatial control of cell
attachment. We speculate that our results can enable the widespread use of high-aspect-ratio nanotopograhy applications in
mechanics, optics, and biomedicine.
KEYWORDS: nanoimprint lithography, high aspect ratio, thiol−ene-epoxy, cells, biomechanics, cell attachment, protein patterning,
nanoscale
... Lateral flow tests [142], otherwise called lateral flow immunochromatographic assessments, are straightforward and simple paperbased devices which are gadget-planned to recognize the presence of an objective analyte in a fluid sample without requiring any specific and exorbitant hardware. Lateral flow assays depend on a progression of capillary beds, for example, bits of permeable paper [143], microstructured polymer [144,145], or sintered polymer. Each of these pads has the ability to spontaneously migrate liquid samples (e.g., saliva, blood, urine). ...
A novel coronavirus of zoonotic origin (SARS-CoV-2) has recently been recognized in patients with acute respiratory disease. COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coronaviruses. The drastic increase in the number of coronavirus and its genome sequence have given us an unprecedented opportunity to perform bioinformatics and genomics analysis on this class of viruses. Clinical tests like PCR and ELISA for rapid detection of this virus are urgently needed for early identification of infected patients. However, these techniques are expensive and not readily available for point-of-care (POC) applications. Currently, lack of any rapid, available, and reliable POC detection method gives rise to the progression of COVID-19 as a horrible global problem. To solve the negative features of clinical investigation, we provide a brief introduction of the general features of coronaviruses and describe various amplification assays, sensing, biosensing, immunosensing, and aptasensing for the determination of various groups of coronaviruses applied as a template for the detection of SARS-CoV-2. All sensing and biosensing techniques developed for the determination of various classes of coronaviruses are useful to recognize the newly immerged coronavirus, i.e., SARS-CoV-2. Also, the introduction of sensing and biosensing methods sheds light on the way of designing a proper screening system to detect the virus at the early stage of infection to tranquilize the speed and vastity of spreading. Among other approaches investigated among molecular approaches and PCR or recognition of viral diseases, LAMP-based methods and LFAs are of great importance for their numerous benefits, which can be helpful to design a universal platform for detection of future emerging pathogenic viruses.
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
Stimuli-responsive surfaces are of practical importance for applications ranging from enhanced mixing of reagents in lab-on-a-chip systems until probing cellular traction forces. Non-destructive reversible bending of cilia-inspired magnetic pillars can be used for controlled transportation of non-magnetic objects and bio-inspired sensing. Magnetic actuation of micropillars suspended in liquids allows controlled mixing, propelling, and stirring of fluids as well as droplet manipulation, which are important for various applications including generation of cell spheroids and droplet coalescence in microfluidic systems. In order to expand their practical applications, fabrication processes capable of rapid prototyping have to be developed. Inspired by biological cilia and their functionalities, actuating hairy surfaces are herein fabricated and implemented to manipulate both microbeads and droplets. The artificial cilia are based on microscale magnetic pillar arrays made of flexible polydimethylsiloxane functionalized with magnetic microparticles. The arrays are fabricated by a new method using patterned molds that relies on cryogenic separation to produce transparent cilia-inspired arrays without requiring manual interference to clean the templates during the process. Magnetic actuation of the pillar arrays is demonstrated in isopropanol and silicone oil. Filling with oil yields magnetically responsive slippery lubricated surfaces allowing directional motion of droplets by repetitive bending and recovery of the flexible magnetic pillars. The achieved structures allow manipulation of microbeads and droplets which is uncommon even at the sub-mm scale; directional motion is demonstrated for 250 μm–550 μm sized droplets. Droplet transportation is facilitated by extremely low hysteresis and a high degree of omnidirectional bending of the pillar array.
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
... Given the array pitch value of 30 μm and the low Young's modulus of PDMS, it is necessary to keep the pillars immersed in isopropanol or oil during application to avoid capillary force induced collapse of the pillars [ Fig. S6(b)]. [33][34][35] The magnetic pillars can be recovered from the collapsed state to the functioning state by sonication. ...
Stimuli-responsive surfaces are of practical importance for applications ranging from enhanced mixing of reagents in lab-on-a-chip systems until probing cellular traction forces. Non-destructive reversible bending of cilia-inspired magnetic pillars can be used for controlled transportation of non-magnetic objects and bio-inspired sensing. Magnetic actuation of micropillars suspended in liquids allows controlled mixing, propelling, and stirring of fluids as well as droplet manipulation, which are important for various applications including generation of cell spheroids and droplet coalescence in microfluidic systems. In order to expand their practical applications, fabrication processes capable of rapid prototyping have to be developed. Inspired by biological cilia and their functionalities, actuating hairy surfaces are herein fabricated and implemented to manipulate both microbeads and droplets. The artificial cilia are based on microscale magnetic pillar arrays made of flexible polydimethylsiloxane functionalized with magnetic microparticles. The arrays are fabricated by a new method using patterned molds that relies on cryogenic separation to produce transparent cilia-inspired arrays without requiring manual interference to clean the templates during the process. Magnetic actuation of the pillar arrays is demonstrated in isopropanol and silicone oil. Filling with oil yields magnetically responsive slippery lubricated surfaces allowing directional motion of droplets by repetitive bending and recovery of the flexible magnetic pillars. The achieved structures allow manipulation of microbeads and droplets which is uncommon even at the sub-mm scale; directional motion is demonstrated for 250 μm–550 μm sized droplets. Droplet transportation is facilitated by extremely low hysteresis and a high degree of omnidirectional bending of the pillar array.
... The innovation includes the conveyance of liquids (e.g., pee) through pieces of permeable paper, fine beds, sintered polymers or microstructured polymers. 65 The system involves different parts and steps. An example cushion goes about as a wipe and retains the liquids. ...
The innovative immunomodulation technologies are excellent tools to synthesis the novel antibodies. The conventional methods are potentially replaced by more précised techniques to obtain the desired antibodies. Particularly the hybridoma technique used to produce the antibodies against targeted antigens. The pathogenic microorganisms, autoimmune agents and other malignant entities can be controlled by using these innovative immunomodules. Moreover, the abundant powerful toxic substances can be handled with such monoclonal antibodies. These analytical acculturated or chimeric murine antibodies have a couple of imperatives and complexities. In order to vanquish these problems, late advancements in inherited building procedures and phage indicate framework have conceded the making of exceedingly recombinant antibodies that are specific. Moreover, highly specified recombinant antibodies are produced by the recent advancements in genetic engineering procedures and phage display procedure. The antibodies chase for novel remedial medications outfitted with upgraded immune protective capacities such as drawing in invulnerable effector capacities, viable advancement of combination proteins, productive tumor tissue infiltration and high-partiality antibodies coordinated against targets. Propelled neutralizer building systems have broad practices in the fields of diagnostics, biotechnology, immunology, and helpful prescriptions. Notwithstanding, there is restricted information with respect to dynamic neutralizer advancement approaches. Consequently, our ability to comprehend the customary polyclonal and monoclonal antibodies and advanced immunizer designing strategies has widened the clinical use imaginative counter acting agents.
... Their presence facilitates spotting of oligonucleotide probes owing to their capacity to induce wicking, which enables self-alignment and uniform distribution of probe liquid across the structured areaa trait these templates share with "synthetic microfluidic paper" substrates. 29,31 Thus, far, "synthetic microfluidic paper" has been produced through photopolymerization where compartments of slanted and interlocked micropillars provide high surface area and capillarity to induce wicking. For any of these structures, the possibility of arranging multiple probes in close proximity is key to obtaining test strips with enhanced analytical capability. ...
We describe the use of periodic micropillar arrays, produced from cyclic olefin copolymer using high-fidelity microfabrication, as templates for colorimetric DNA detection. The assay involves PCR-amplified gene markers for E. coli O157 (rfbO157, eae, vt1 and vt2) incorporating a detectable digoxigenin label, which is revealed through an immunoenzymatic process following hybridization with target-specific oligonucleotide capture probes. The capacity of micropillar arrays to induce wicking is used to distribute and confine capture probes with spatial control, making it possible to achieve a uniform signal while allowing multiple, independent probes to be arranged in close proximity on the same substrate. The kinetic profile of color pigment formation on the surface was followed using absorbance measurements, showing maximum signal increase between 20 and 60 min of reaction time. The relationship between microstructure and colorimetric signal was investigated through variation of geometric parameters, such as pitch (10-50 μm), pillar diameter (5-40 μm), and height (16-48 μm). Our findings suggest that signal intensity is largely influenced by the edges of the pillars and less by their height such that it deviates from a linear relationship when both aspect ratio and pillar density become very high. A theoretical model used to simulate the changes in surface composition at the molecular level suggests that differences in the temporal and spatial accumulation of assay components account for this observation.
... The highest porosity was shown by the paper composed of a 3:1 mixture of sugarcane bagasse and Pinus fi bers, which could lead to low permeability of the paper. Highly porous papers are used in biological assays, as alternatives to nitrocellulose and microcapillary membranes (Hansson et al., 2016), indicating a possible use for this paper. However, the paper obtained using 100% sugarcane bagasse fi ber (sample 2) presented porosity similar to that of the traditional paper produced using a mixture of Pinus and Eucalyptus (sample 3). ...
Sugarcane bagasse, a waste material generated by the sugar-alcohol industry, is rich in lignocellulosic components such as cellulose and hemicellulose. The bagasse can be employed as a raw material in the pulp and paper industry, but is currently rarely used for this purpose, due to the availability of traditional sources such as Eucalyptus and Pinus. The objective of this work was to compare the physical and mechanical properties of papers produced using the cellulose extracted from sugarcane, Eucalyptus, and Pinus by the Kraft method. Four paper samples were produced using cellulose obtained from the following fiber sources: (I) 100% sugarcane bagasse; (II) 100% Eucalyptus; (III) 75% Eucalyptus + 25% Pinus; (IV) 75% sugarcane bagasse + 25% Pinus. Physical and mechanical tests were performed based on regulatory methodologies of the paper industry. The results indicated that the physical and mechanical characteristics of the paper produced from the sugarcane cellulose were similar to those of the traditional paper produced using Eucalyptus. Particular features such as good tearing resistance and tensile strength, as well as increased porosity and moisture, could be adjusted according to the intended use of the paper. Therefore, sugarcane bagasse can be considered a sustainable alternative to Eucalyptus and Pinus for the production of high quality paper, adding value to this agricultural residue.
... The microstructured surfaces are made from Ostemer 220 (Mercene Labs, Stockholm, Sweden), a UV-curing Off-Stoichiometry-Thiol-Ene (OSTE) resin, with excellent lithographic patterning, previously used to create complex slanted structures 29 . The samples are manufactured as follows. ...
Microstructured surfaces that control the direction of liquid transport are not only ubiquitous in nature, but they are also central to technological processes such as fog/water harvesting, oil-water separation, and surface lubrication. However, a fundamental understanding of the initial wetting dynamics of liquids spreading on such surfaces is lacking. Here, we show that three regimes govern microstructured surface wetting on short time scales: spread, stick, and contact line leaping. The latter involves establishing a new contact line downstream of the wetting front as the liquid leaps over specific sections of the solid surface. Experimental and numerical investigations reveal how different regimes emerge in different flow directions during wetting of periodic asymmetrically microstructured surfaces. These insights improve our understanding of rapid wetting in droplet impact, splashing, and wetting of vibrating surfaces and may contribute to advances in designing structured surfaces for the mentioned applications.
Self-powered microfluidics presents a revolutionary approach to address the challenges of healthcare in decentralized and point-of-care settings where limited access to resources and infrastructure prevails or rapid clinical decision-making is critical. These microfluidic systems exploit physical and chemical phenomena, such as capillary forces and surface tension, to manipulate tiny volumes of fluids without the need for external power sources, making them cost-effective and highly portable. Recent technological advancements have demonstrated the ability to preprogram complex multistep liquid operations within the microfluidic circuit of these standalone systems, which enabled the integration of sensitive detection and readout principles. This chapter first addresses how the accessibility to in vitro diagnostics can be improved by shifting toward decentralized approaches like remote microsampling and point-of-care testing. Next, the crucial role of self-powered microfluidic technologies to enable this patient-centric healthcare transition is emphasized using various state-of-the-art examples, with a primary focus on applications related to biofluid collection and the detection of either proteins or nucleic acids. This chapter concludes with a summary of the main findings and our vision of the future perspectives in the field of self-powered microfluidic technologies and their use for in vitro diagnostics applications.
Microfluidic capture chips are useful for preparing or analyzing a wide range of different chemical, biological, and medical samples. A typical microfluidic capture chip contains features that capture certain targets (i.e. molecules, particles, cells) as they flow through the chip. However, creating optimal capture chip designs is difficult because of the inherent relationship between capture efficiency and flow resistance: as more capture features are added to the chip, the capture efficiency increases, but the additional features slow the flow of fluid through the chip. This paper introduces the use of multi-objective optimization to generate capture chip designs that balance the trade-off between maximizing target capture efficiency and minimizing resistance to fluid flow. Design automation for this important class of microfluidic chips has not been attempted previously. Our approach automatically produces a Pareto front of non-dominated chip designs in a reasonable amount of time, and most of these designs have comparable capture efficiency to hand-designed chips with far lower flow resistance. By choosing from the chip designs on the Pareto front, a user can obtain high capture efficiency without exceeding the flow resistance constraints of their application.
This review describes our recent studies about “fluid-fluid interfacial energy driven 3D structure emergence in a micropillar scaffold (FLUID3EAMS)” and its application. The FLUID3EAMS generates a 3D droplet (or hydrogel bead) array in a micropillar scaffold by a simple phenomenon that a fluid-fluid interface passes through the scaffold. The method to realize the phenomenon will be a powerful tool for application requiring ordered or arrayed microdroplets in biophysics, biology, or tissue engineering.
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We investigate the use of periodic micropillar arrays produced by high-fidelity microfabrication with cyclic olefin polymers for solid-phase immunoassays. These three-dimensional (3D) templates offer higher surface-to-volume ratios than two-dimensional substrates, making it possible to attach more antibodies and so increase the signal obtained by the assay. Micropillar arrays also provide the capacity to induce wicking, which is used to distribute and confine antibodies on the surface with spatial control. Micropillar array substrates are modified by using oxygen plasma treatment, followed by grafting of (3-aminopropyl)triethoxysilane for binding proteins covalently using glutaraldehyde as a cross-linker. The relationship between microstructure and fluorescence signal was investigated through variation of pitch (10-50 μm), pillar diameter (5-40 μm), and pillar height (5-57 μm). Our findings suggest that signal intensity scales proportionally with the 3D surface area available for performing solid-phase immunoassays. A linear relationship between fluorescence intensity and microscale structure can be maintained even when the aspect ratio and pillar density both become very high, opening the possibility of tuning assay response by design such that desired signal intensity is obtained over a wide dynamic range compatible with different assays, analyte concentrations, and readout instruments. We demonstrate the versatility of the approach by performing the most common immunoassay formats-direct, indirect, and sandwich-in a qualitative fashion by using colorimetric and fluorescence-based detection for a number of clinically relevant protein markers, such as tumor necrosis factor alpha, interferon gamma (IFN-γ), and spike protein of severe acute respiratory syndrome coronavirus 2. We also show quantitative detection of IFN-γin serum using a fluorescence-based sandwich immunoassay and calibrated samples with spike-in concentrations ranging from 50 pg/mL to 5 μg/mL, yielding an estimated limit of detection of ∼1 pg/mL for arrays with high micropillar density (11561 per mm2) and aspect ratio (1:11.35).
At-home rapid antigen test (RAT) kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are valuable public health tools during the present coronavirus disease (COVID-19) pandemic. They provide fast identification of coronavirus infection, which can help to reduce the transmission rates and burden on the healthcare system. However, they have lower sensitivity compared to the reverse transcription polymerase chain reaction (RT-PCR) tests. One of the reasons for the lower sensitivity is due to the RAT color indicators being indistinct or invisible to the naked eye after the measurements. For this reason, we present a proof of concept of a novel approach, through which we investigated anonymously provided at-home RAT kit results by using our in-house open-source image processing scripts developed for affordable Raspberry Pi computer and Raspberry Pi HQ camera systems. Therefore, we aimed at minimizing the human-related analysis errors for such kits and believe that the present computer vision-based assessment framework can contribute to reducing delayed quarantines of infected individuals and the spread of the current infectious disease.
The various high aspect ratio micro/nano structures that are duplicated by the widely applicable micro/nanomolding process would require excellent wettability of the structured mold for full filling of the liquid-like materials into microcavities. Herein, by employing molecular dynamics (MD) simulations, the influence of a monolayer graphene (MLG) on the wetting behaviors of grooved copper is thoroughly investigated, indicating that MLG is an effective approach in modulating the wettability of the structured copper surfaces. Moreover, the extracted outcomes signify that the coating with MLG reduces remarkably the required activation energy for the infiltration of water molecules into the copper groove, thereby triggering the wetting transition from the Cassie-Baxter (CB) to the Wenzel (WZ) state. In addition, by varying the coating locations and dimension of the MLG, it is unveiled that the sidewall coating of MLG plays a crucial role in reducing the free energy barrier needed to surmount the transition state. Interestingly, as the coating height of sidewall MLG increases, the energy barrier is reduced, and the grooved surface becomes more attractive to water molecular, attaining a stable WZ state by employing a height beyond the critical value of MLG coating of 12.4 Å in our model. Our work provides useful insights into the tunable wettability of the grooved surfaces by nanocoating engineering, suggesting that MLG can be an effective coating solution in the fabrication of novel micro/nanostructures with high aspect ratios.
Decades of research have shown that biosensors using photonic circuits fabricated using CMOS processes can be highly sensitive, selective, and quantitative. Unfortunately, the cost of these sensors combined with the complexity of sample handling systems has limited use of such sensors in clinical diagnostics. We present a new “disposable photonics” sensor platform in which rice-sized (1 x 4 mm) silicon nitride ring resonator sensor chips are paired with plastic micropillar fluidic cards for sample handling and optical detection. We demonstrate the utility of the platform in the context of detecting human antibodies to SARS-CoV-2, both in convalescent COVID-19 patients and for subjects undergoing vaccination. Given its ability to provide quantitative data on human samples in a simple, low-cost format, we anticipate that this platform will find broad utility in clinical diagnostics for a broad range of assays.
The patterning dynamics of confined immiscible fluids has inspired an elegant and versatile approach to building periodic three-dimensional multi-material architectures. The technique extends to triphasic composites, three-dimensional droplet networks and even biological tissues.
In optical biosensing, silk fibroin (SF) appears as a promising alternative where other materials, such as paper, find limitations. Besides its excellent optical properties and unmet capacity to stabilize biomacromolecules, SF in test strips exhibit additional functions, i.e. capillary pumping activity of 1.5 mm s-1, capacity to filter blood cells thanks to its small, but tuneable, nanoporosity and enhanced biosensing sensitivity. The bulk functionalization of SF with the enzymes glucose oxidase and peroxidase and the mediator ABTS produces colourless transparent SF films that respond to blood glucose tripling the sensitivity of conventional ABTS-based assays. This enhanced sensitivity results from the formation of SF-ABTS complexes, where SF becomes part of the bioassay. Additionally, SF films triple the durability of most stable cellulose-based sensors. Although demonstrated for glucose, SF microfluidic test strips may incorporate other optical bioassays, e.g. immunoassays, with the aim to transfer them from central laboratories to the patient’s care.
While there is a steady growth in the number of microfluidics applications, the search for an optimal material that delivers the diverse characteristics needed for the numerous tasks is still nowhere close to being settled. Often overlooked and still underrepresented, the thiol-ene family of polymer materials has an enormous potential for applications in organs-on-a-chip, droplet productions, microanalytics and point of care testing. In this review, the main characteristics of the thiol-ene materials are given, and advantages and drawbacks with respect to their potential in microfluidic chip fabrication are critically as-sessed. Select applications, which exploit the versatility of the thiol-ene polymers, are presented and discussed. It is con-cluded that, in particular, the rapid prototyping possibility combined with the material’s resulting mechanical strength, solvent resistance, and biocompatibility, as well as the inherently easy surface functionalization, are strong factors to make thiol-ene polymers strong contenders for promising future materials for many biological, clinical and technical lab-on-a-chip applications.
Microfluidic paper analytical devices (µPADs) is smart and accessible substituent to traditional counterparts in point-of-care tests (POCT), which exploited delicate control over passive fluid in microscale for rich functions. In this work, we are extend-ing such control by introducing novel ways to generate 1D and 2D gradient on µPADs. It is achieved by using paper capillary-based serial sampling. The paper capillary is composed of a concaved paper channel sealed with tape, with test pads properly distributed aside. In such a structure, the liquid can not only quickly and automatically flow along the capillary, but also be continuously consumed by the peripheral test pads. Thus, when we do serial sampling, abnormal liquid chasing effect can be observed, where the later liquid sample chases and surpasses the earlier parts in the paper capillary, leading to reversely ordered sample distribution compared with that in a typical glass capillary. This specialty allows for fast, ordered and tunable sequential sampling, enables efficient generation of 1D and 2D concentration gradient with one, two and even three components on µPADs. Besides, we verified the applicability of this technique for arrayed assays, including 1D serial dilution-based metal ion colorimetry and 2D bacterial antibiotic susceptibility test for synergic effect evaluations, which paves the way for high-throughput sample analysis and information-rich condition screening on µPADs.
Chemiluminescence immunoassay (CLIA) has been greatly developed in the past several decades due to its good sensitivity and specificity. Nowadays, CLIA has been highly improved with novel nanomaterials and newly-developed technologies. The advancement of CLIA combined with relevant technologies are reviewed in the paper, including enhanced chemiluminescent, antibody preparation, aptamer selection, nanomaterials assisted CLIA, and CLIA coupling with newly-developed technologies. Finally, some critical challenges are discussed in the field and the future development direction of CLIA is prospected. The review will be of great significance for CLIA basic research and practical applications in the fields of biomedical diagnostics, food and drug testing, environmental monitoring, and other fields.
Tunable and responsive surfaces offer routes to multiple functionalities ranging from superhydrophobic surfaces to controlled adhesion. Inspired by cilia structure in the respiratory pathway, magnetically responsive periodic arrays of flexible and magnetic thiol–ene micropillars are fabricated. Omnidirectional collective bending of the pillar array in magnetic field is shown. Local non‐contact actuation of a single pillar is achieved using an electromagnetic needle to probe the responsiveness and the elastic properties of the pillars by comparing the effect of thiol–ene crosslinking density to pillar bending. The suitable thiol–ene components for flexible and stiff magnetic micropillars and the workable range of thiol‐to‐allyl ratio are identified. The wettability of the magnetic pillars can be tailored by chemical and topography modification of the pillar surface. Low‐surface‐energy self‐assembled monolayers are grafted by UV‐assisted surface activation, which is also used for surface topography modification by covalent bonding of micro‐ and nanoparticles to the pillar surface. The modified thiol–ene micopillars are resistant to capillarity‐driven collapse and they exhibit low contact angle hysteresis, allowing water droplet motion driven by repeated bending and recovery of the magnetic pillars in an external magnetic field. Transport of polyethylene microspheres is also demonstrated. Flexible liquid‐repellent thiol–ene magnetic micropillars can be used to transport droplets and beads by magnetically actuated motion. The unique properties of thiol–ene allow for both flexibility and surface topography of the micropillars to be tailored by tuning composition and reactive chemistry. Thiol–ene pillars decorated with colloidal micro‐ and nanoparticles exhibit superhydrophobicity, enabling directional water droplet motion.
The rapid development of and large market for medical diagnostics necessitate point-of-care testing (POCT) with superior sensitivity, miniaturization, multifunctionality and high integration. Thus, flexible substrates with complex structures that provide multiple functions are in demand. Herein, we present multistructured pseudo-papers (MSPs) as a platform for building flexible microfluidics. Flexible and freestanding MSPs are generated by the self-assembly of colloidal silica crystals or core-shell copolymer elastic colloidal crystals on microcavity PDMS molds to form photonic crystals (PCs). Nitrocellulose (NC) multistructured pseudo-papers (NC MSPs) were obtained by etching SiO 2 PCs after NC precursor infiltration, while elastic copolymer (EC) multistructured pseudo-papers (EC MSPs) were directly peeled off the mold; both types of freestanding MSPs have ordered micropillars and nanocrystal structures and presented unique properties such as pumpless liquid transport and fluorescence and chemiluminescence (CL) enhancement. MSPs with designed patterns were fabricated by patterned PDMS molds, and complicated microfluidic chips were used to generate MSPs by utilizing these patterns as liquid channels. The MSPs were used for fabricating microfluidic sensors for human cardiac marker and cancer marker sensing; the features of these bioinspired MSPs indicate their potential value for sensitive sensing, which will enable them to find broader applications in many fields.
Deterministic lateral displacement (DLD), a hydrodynamic, microfluidic technology, was first reported by Huang et al. in 2004 to separate particles on the basis of size in continuous flow with a resolution of down to 10 nm. For 10 years, DLD has been extensively studied, employed and modified by researchers in terms of theory, design, microfabrication and application to develop newer, faster and more efficient tools for separation of millimetre, micrometre and even sub-micrometre sized particles. To extend the range of potential applications, the specific arrangement of geometric features in DLD has also been adapted and/or coupled with external forces (e.g. acoustic, electric, gravitational) to separate particles on the basis of other properties than size such as the shape, deformability and dielectric properties of particles. Furthermore, investigations into DLD performance where inertial and non-Newtonian effects are present have been conducted. However, the evolvement and application of DLD has not yet been reviewed. In this paper, we collate many interesting publications to provide a comprehensive review of the development and diversity of this technology but also provide scope for future direction and detail the fundamentals for those wishing to design such devices for the first time.
A simple approach to the evaluation of blood coagulation using a microfluidic paper-based lateral flow assay (LFA) device for point-of-care (POC) and self-monitoring screening is reported. The device utilizes whole blood, without the need for prior separation of plasma from red blood cells (RBC). Experiments were performed using animal (rabbit) blood treated with trisodium citrate to prevent coagulation. CaCl2 solutions of varying concentrations are added to citrated blood, producing Ca(2+) ions to re-establish the coagulation cascade and mimic different blood coagulation abilities in vitro. Blood samples are dispensed into a paper-based LFA device consisting of sample pad, analytical membrane and wicking pad. The porous nature of the cellulose membrane separates the aqueous plasma component from the large blood cells. Since the viscosity of blood changes with its coagulation ability, the distance RBCs travel in the membrane in a given time can be related to the blood clotting time. The distance of the RBC front is found to decrease linearly with increasing CaCl2 concentration, with a travel rate decreasing from 3.25 mm min(-1) for no added CaCl2 to 2.2 mm min(-1) for 500 mM solution. Compared to conventional plasma clotting analyzers, the LFA device is much simpler and it provides a significantly larger linear range of measurement. Using the red colour of RBCs as a visible marker, this approach can be utilized to produce a simple and clear indicator of whether the blood condition is within the appropriate range for the patient's condition.
During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial-mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion.
In recent years, a relatively new type of negative photoresist, EPON SU-8, has received a lot of attention in the MEMS field because of its excellent lithography properties. Significant research efforts have been made to study the lithographic properties of SU-8 to obtain high aspect ratio microstructures with good sidewall quality. Currently, selec-tion of optimal wavelengths of the UV light for lithographic and reduction of the diffraction effects are believed to be the two most important factors for achieving high-quality lithography of SU-8 as reported in the litera-ture. Other reported efforts also include modifications of the chemical properties of SU-8 for better lithographic quality. We report a study on stress reduction during the postbaking process and the effects on lithog-raphy of ultra-thick high aspect ratio SU-8 microstructures. Our research proves that aspect ratios up to 40:1 in isolated open field structures of thicknesses between 1 and 1.5 mm can be obtained without any modi-fications of the resist chemistry or changes in light spectrum applied from a standard broadband UV source. The principal factor in this achieve-ment is the reduction of internal stress during the postexposure bake process that eliminates large plastic deformations present during stan-dard bake procedures. This process may be used for the fabrication of ultra-thick high aspect ratio microstructures that have to date only been obtainable using x-ray lithography-based LIGA processes. © 2004 Society of Photo-Optical Instrumentation Engineers. [ Subject terms: SU-8; ultraviolet LIGA; thick resist; high aspect ratio; microstruc-tures; MEMS. Paper 03033 received Apr. 4, 2003; revised manuscript received Dec. 10, 2003; accepted for publication Feb. 12, 2004.
Cell migration plays a major role in many fundamental biological processes, such as morphogenesis, tumor metastasis, and wound healing. As they anchor and pull on their surroundings, adhering cells actively probe the stiffness of their environment. Current understanding is that traction forces exerted by cells arise mainly at mechanotransduction sites, called focal adhesions, whose size seems to be correlated to the force exerted by cells on their underlying substrate, at least during their initial stages. In fact, our data show by direct measurements that the buildup of traction forces is faster for larger substrate stiffness, and that the stress measured at adhesion sites depends on substrate rigidity. Our results, backed by a phenomenological model based on active gel theory, suggest that rigidity-sensing is mediated by a large-scale mechanism originating in the cytoskeleton instead of a local one. We show that large-scale mechanosensing leads to an adaptative response of cell migration to stiffness gradients. In response to a step boundary in rigidity, we observe not only that cells migrate preferentially toward stiffer substrates, but also that this response is optimal in a narrow range of rigidities. Taken together, these findings lead to unique insights into the regulation of cell response to external mechanical cues and provide evidence for a cytoskeleton-based rigidity-sensing mechanism.
In this article we introduce a novel polymer platform based on off-stoichiometry thiol-enes (OSTEs), aiming to bridge the gap between research prototyping and commercial production of microfluidic devices. The polymers are based on the versatile UV-curable thiol-ene chemistry but takes advantage of off-stoichiometry ratios to enable important features for a prototyping system, such as one-step surface modifications, tuneable mechanical properties and leakage free sealing through direct UV-bonding. The platform exhibits many similarities with PDMS, such as rapid prototyping and uncomplicated processing but can at the same time mirror the mechanical and chemical properties of both PDMS as well as commercial grade thermoplastics. The OSTE-prepolymer can be cast using standard SU-8 on silicon masters and a table-top UV-lamp, the surface modifications are precisely grafted using a stencil mask and the bonding requires only a single UV-exposure. To illustrate the potential of the material we demonstrate key concepts important in microfluidic chip fabrication such as patterned surface modifications for hydrophobic stops, pneumatic valves using UV-lamination of stiff and rubbery materials as well as micromachining of chip-to-world connectors in the OSTE-materials.
Mesoscale hierarchical helical structures with diverse functions are abundant in nature. Here we show how spontaneous helicity
can be induced in a synthetic polymeric nanobristle assembling in an evaporating liquid. We use a simple theoretical model
to characterize the geometry, stiffness, and surface properties of the pillars that favor the adhesive self-organization of
bundles with pillars wound around each other. The process can be controlled to yield highly ordered helical clusters with
a unique structural hierarchy that arises from the sequential assembly of self-similar coiled building blocks over multiple
length scales. We demonstrate their function in the context of self-assembly into previously unseen structures with uniform,
periodic patterns and controlled handedness and as an efficient particle-trapping and adhesive system.
The amazing climbing ability of geckos has attracted the interest of philosophers and scientists alike for centuries. However, only in the past few years has progress been made in understanding the mechanism behind this ability, which relies on submicrometre keratin hairs covering the soles of geckos. Each hair produces a miniscule force approximately 10(-7) N (due to van der Waals and/or capillary interactions) but millions of hairs acting together create a formidable adhesion of approximately 10 N x cm(-2): sufficient to keep geckos firmly on their feet, even when upside down on a glass ceiling. It is very tempting to create a new type of adhesive by mimicking the gecko mechanism. Here we report on a prototype of such 'gecko tape' made by microfabrication of dense arrays of flexible plastic pillars, the geometry of which is optimized to ensure their collective adhesion. Our approach shows a way to manufacture self-cleaning, re-attachable dry adhesives, although problems related to their durability and mass production are yet to be resolved.
Superhydrophobic surfaces have drawn a lot of interest both in academia and in industry because of the self-cleaning properties. This critical review focuses on the recent progress (within the last three years) in the preparation, theoretical modeling, and applications of superhydrophobic surfaces. The preparation approaches are reviewed according to categorized approaches such as bottom-up, top-down, and combination approaches. The advantages and limitations of each strategy are summarized and compared. Progress in theoretical modeling of surface design and wettability behavior focuses on the transition state of superhydrophobic surfaces and the role of the roughness factor. Finally, the problems/obstacles related to applicability of superhydrophobic surfaces in real life are addressed. This review should be of interest to students and scientists interested specifically in superhydrophobic surfaces but also to scientists and industries focused in material chemistry in general.
Viable tumour-derived epithelial cells (circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease. Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for the detection, characterization and monitoring of non-haematologic cancers. The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity. Here we describe the development of a unique microfluidic platform (the 'CTC-chip') capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody (EpCAM)-coated microposts under precisely controlled laminar flow conditions, and without requisite pre-labelling or processing of samples. The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 (99%) samples, with a range of 5-1,281 CTCs per ml and approximately 50% purity. In addition, CTCs were isolated in 7/7 patients with early-stage prostate cancer. Given the high sensitivity and specificity of the CTC-chip, we tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. Thus, the CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biology research and clinical cancer management, including the detection, diagnosis and monitoring of cancer.
At the convergence of organic electronics and biology, organic bioelectronics attracts great scientific interest. The potential applications of organic semiconductors to reversibly transmit biological signals or stimulate biological tissues inspires many research groups to explore the use of organic electronics in biological systems. Considering the surfaces of movable living tissues being arbitrarily curved at physiological environments, the flexibility of organic bioelectronic devices is of paramount importance in enabling stable and reliable performances by improving the contact and interaction of the devices with biological systems. Significant advances in flexible organic bio-electronics have been achieved in the areas of flexible organic thin film transistors (OTFTs), polymer electrodes, smart textiles, organic electrochemical ion pumps (OEIPs), ion bipolar junction transistors (IBJTs) and chemiresistors. This review will firstly discuss the materials used in flexible organic bioelectronics, which is followed by an overview on various types of flexible organic bioelectronic devices. The versatility of flexible organic bioelectronics promises a bright future for this emerging area.
Fabrication of complex 3D objects using folding of thin films is a novel and very attractive research field. This manuscript overviews recent progress in development, investigation, and application of self-folding polymer films which are able to fold and form various 3D structures. The review discusses the basic principles of design of self-folding films, fabrication of self-folding films, possibilities to build complex 3D shapes, their responsive properties, and applications.
We report the design, fabrication and evaluation of an array of microdevices composed of high aspect ratio PDMS pillars, dedicated to the study of tumour spheroid mechanical properties. The principle of the microdevice is to confine a spheroid within a circle of micropillars acting as peripheral flexible force sensors. We present a technological process for fabricating high aspect ratio micropillars (300 μm high) with tunable feature dimensions (diameter and spacing) enabling production of flexible PDMS pillars with a height comparable to spheroid sizes. This represents an upscale of 10 along the vertical direction in comparison to more conventional PDMS pillar force sensors devoted to single cell studies, while maintaining their force sensitivity in the same order of magnitude. We present a method for keeping these very high aspect ratio PDMS pillars stable and straight in liquid solution. We demonstrate that microfabricated devices are biocompatible and adapted to long-term spheroid growth. Finally, we show that the spheroid interaction with the micropillars' surface is dependent on PDMS cellular adhesiveness. Time-lapse recordings of growth-induced micropillars' bending coupled with a software program to automatically detect and analyse micropillar displacements are presented. The use of these microdevices as force microsensors opens new prospects in the fields of tissue mechanics and pharmacological drug screening.
High aspect-ratio micropillars are in strong demand for microtechnology, but their realization remains a difficult challenge, especially when attempted with soft materials. Here we present a direct drawing-based technique for fabricating micropillars with poly(dimethylsiloxane). Despite the material's extreme softness, our technique enables routine realization of micropillars exceeding 2,000 μm in height and 100 in aspect-ratio. It also supports in situ integration of microspheres at the tips of the micropillars. As a validation of the new structure's utility, we configure it into airflow sensors, in which the micropillars and microspheres function as flexible upright waveguides and self-aligned reflectors, respectively. High-level bending of the micropillar under an airflow and its optical read-out enables mm s(-1) scale-sensing resolution. This new scheme, which uniquely integrates high aspect-ratio elastomeric micropillars and microspheres self-aligned to them, could widen the scope of soft material-based microdevice technology.
This new edition comes 16 years after the previous one, and it has about 30% more pages. The format remains the same: tables of compounds arranged by structural type list all manner of useful properties, including not only melting and boiling points but density, refractive index, heat capacity, dielectric constant, etc. For this edition, six more properties have been added, including compressibility properties and thermal conductivity. The second part of the book is devoted, as before, to methods that have been reported for the purification of individual compounds, with the results of the processes. Although this is very helpful, it is not as satisfying as it might be, for there is little or no critical evaluation when several methods are described. The increased size of this edition is largely due to the inclusion of 150 solvents that were not listed before. Another change is in the references (over 7000exclamation), where the method of citing has been altered to match that used in Chemical Abstracts (year, volume, page, rather than volume, page, year). This must have been a lost of work; was the gain in utility really worth it. In any event, the publishers are to be commended for having selected very clearly distinguishable type faces for the numerals used for the year, volume, and pages.
A new class of cellular micro-scale truss structures formed from a three-dimensional interconnected pattern of self-propagating photopolymer waveguides were presented. The diameter of the waveguide was dependent on the exposed area and the length was primarily dependent on the incident energy of the light and the photo-absorption properties of the polymer. The diameter of the resulting waveguide is found to be slightly larger than the diameter of the single aperture as the prolonged exposure causes the waveguide to thicken. The micro-truss structure is 7.8 mm in height and features a repeating octahedral-type unit cell. The microstructures with increased and reduced open volume fraction are possible such that the upper bound on open volume fractions determined by the self-supporting ability of the structure while lower bound limited by the ability to remove the uncured monomer after the polymerization process.
A major technical hurdle in microfluidics is the difficulty in achieving high fidelity lithographic patterning on polydimethylsiloxane (PDMS). Here, we report a simple yet highly precise and repeatable PDMS surface micromachining method using direct photolithography followed by reactive ion etching (RIE). Our method to achieve surface patterning of PDMS applied an O(2) plasma treatment to PDMS to activate its surface to overcome the challenge of poor photoresist adhesion on PDMS for photolithography. Our photolithographic PDMS surface micromachining technique is compatible with conventional soft lithography techniques and other silicon-based surface and bulk micromachining methods. To illustrate the general application of our method, we demonstrated fabrication of large microfiltration membranes and free-standing beam structures in PDMS.
The lower part of polymeric nanopillars is made mechanically stiff by surrounding it with metal, while the top part of the pillars is soft. The metal-shell-free tops of the pillars could be used for fabricating hollow structures or decorated with functional materials. This mechanical reinforcement shows stability against capillary-force-induced clustering and enables applications in a water environment.
Fibrinogen is a major cardiovascular disease risk factor and is an independent predictor of coronary heart disease and stroke. Normal reference levels are approximately 2 to 4 g/L. Elevated levels are associated with the occurrence of cardiovascular disease-related events. The risk of increased bleeding in major surgery is inversely correlated with fibrinogen concentrations for concentrations below the upper limit of the reference interval, i.e., <4 g/L. Determination of the clottable fibrinogen concentration in plasma is, thus, important for the investigation of coagulation disturbances in patients. A novel assay for monitoring plasma fibrinogen content has been developed on the basis of a simple, single use lateral flow microfluidic device. A 15 microL plasma sample is applied to and travels along the microstructured device where it comes into contact with a thrombin reagent. This induces conversion of the soluble fibrinogen to insoluble fibrin and brings about clot formation. Lateral sample flow is arrested as a result of clotting, and the distance along the device at which this occurs has been shown to be dependent on the fibrinogen concentration. The test range was from 1 to 7 g/L of fibrinogen in undiluted patient plasma, and a result could be obtained within 5 min.
Because of their increased mechanical compliance, arrays of high-aspect-ratio microstructures are susceptible to deformation by capillary forces. In the literature, the collapse of a 1D array of tall line patterns during liquid evaporation off of their surface has been attributed to the Laplace pressure difference due to isolated capillary bridges. The same argument has often been simply extended to 2D arrays of tall microstructures to explain the collapse behavior. Using a short-chain polystyrene (PS) melt as a wetting liquid on a 2D array of epoxy micropillars, we showed that the collapse occurred while the micropillars were still completely surrounded by liquid, thus the clustering of micropillars should be caused by the lateral capillary meniscus interaction force rather than by often-reported isolated capillary bridges. We showed that the capillary meniscus interaction force was more than an order of magnitude smaller than that calculated from the Laplace pressure difference due to isolated capillary bridges. This result suggested a much lower critical elastic modulus for stable micropillar arrays, which agreed well with our experimental observation.
The fabrication of hydrogel microstructures based upon poly(ethylene glycol) diacrylates, dimethacrylates, and tetraacrylates patterned photolithographically on silicon or glass substrates is described. A silicon/silicon dioxide surface was treated with 3-(trichlorosilyl)propyl methacrylate to form a self-assembled monolayer (SAM) with pendant acrylate groups. The SAM presence on the surface was verified using ellipsometry and time-of-flight secondary ion mass spectrometry. A solution containing an acrylated or methacrylated poly(ethylene glycol) derivative and a photoinitiator (2,2-dimethoxy-2-phenylacetophenone) was spin-coated onto the treated substrate, exposed to 365 nm ultraviolet light through a photomask, and developed with either toluene, water, or supercritical CO2. As a result of this process, three-dimensional, cross-linked PEG hydrogel microstructures were immobilized on the surface. Diameters of cylindrical array members were varied from 600 to 7 micrometers by the use of different photomasks, while height varied from 3 to 12 micrometers, depending on the molecular weight of the PEG macromer. In the case of 7 micrometers diameter elements, as many as 400 elements were reproducibly generated in a 1 mm2 square pattern. The resultant hydrogel patterns were hydrated for as long as 3 weeks without delamination from the substrate. In addition, micropatterning of different molecular weights of PEG was demonstrated. Arrays of hydrogel disks containing an immobilized protein conjugated to a pH sensitive fluorophore were also prepared. The pH sensitivity of the gel-immobilized dye was similar to that in an aqueous buffer, and no leaching of the dye-labeled protein from the hydrogel microstructure was observed over a 1 week period. Changes in fluorescence were also observed for immobilized fluorophore labeled acetylcholine esterase upon the addition of acetyl acholine.
The stability of structures microfabricated in soft elastomeric polymers is an important concern in most applications that use these structures. Although relevant for several applications, the collapse to the ground of high aspect ratio structures (ground collapse) is still poorly understood. The stability of soft microfabricated high aspect ratio structures versus ground collapse was experimentally assessed, and a new model of ground collapse involving adhesion was developed. Sets of posts with diameters from 0.36 to 2.29 microm were fabricated in poly(dimethylsiloxane) and tested in air or immersed in water and ethanol to change the work of adhesion. The critical aspect ratio (the highest length-to-width ratio for which a post is not at risk of collapsing) was determined as a function of the diameter. The critical aspect ratio in air ranged from 2 to 4 and increased with the diameter. Work of adhesion was found to be determinant for and inversely correlated to stability. These results highlight the role played by adhesion and offer the possibility of improving stability by reducing the work of adhesion. The ground collapse model developed accounted for the main features of structure stability. The results indicate that ground collapse can be a limiting factor in the design of soft polymer structures.
The prognosis for patients suffering from cardiovascular and many other diseases can be substantially improved if diagnosed at an early stage. High performance diagnostic testing using disposable microfluidic chips can provide a platform for realizing this vision. Amic AB (Uppsala, Sweden) has developed a new microfluidic test chip for sandwich immunoassays fabricated by injection molding of the cycloolefin-copolymer Zeonor. A highly ordered array of micropillars within the fluidic chip distributes the sample solution by capillary action. Since wetting of the pillar array surface is the only driving force for liquid distribution precise control of the surface chemistry is crucial. In this work we demonstrate a novel protocol for surface hydrophilization and antibody immobilization on cycloolefin-copolymer test chips, based on direct silanisation of the thermoplastic substrate. Dextran is subsequently covalently coupled to amino groups, thus providing a coating with a low contact angle suitable for antibody immobilization. The contact angle of dextran coated chips is stable for at least two months, which enables production of large batches that can be stored for extended periods of time. We demonstrate the utility of the presented platform and surface chemistry in a C-reactive protein assay with a detection limit of 2.6 ng ml(-1), a dynamic range of 10(2) and a coefficient of variance of 15%.
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