Microfluidic Contact Lenses

Contact lens is a ubiquitous technology used for vision correction and cosmetics. Sensing in contact lenses has emerged as a potential platform for minimally invasive point‐of‐care diagnostics. Here, a microlithography method is developed to fabricate microconcavities and microchannels in a hydrogel‐based contact lens via a combination of laser patterning and embedded templating. Optical microlithography parameters influencing the formation of microconcavities including ablation power (4.3 W) and beam speed (50 mm s^?1) are optimized to control the microconcavity depth (100 µm) and diameter (1.5 mm). The fiber templating method allows the production of microchannels having a diameter range of 100–150 µm. Leak‐proof microchannel and microconcavity connections in contact lenses are validated through flow testing of artificial tear containing fluorescent microbeads (Ø = 1–2 µm). The microconcavities of contact lenses are functionalized with multiplexed fluorophores (2 µL) to demonstrate optical excitation and emission capability within the visible spectrum. The fabricated microfluidic contact lenses may have applications in ophthalmic monitoring of metabolic disorders at point‐of‐care settings and controlled drug release for therapeutics.     

Control of microfluidic flow in amphiphilic fabrics

Woven textile fabrics were designed and constructed from hydrophilic and hydrophobic spun yarns to give planar substrates containing amphiphilic microchannels with defined orientations and locations. Polypropylene fibers were spun to give hydrophobic yarns, and the hydrophilic yarns were spun from a poly(ethylene terephthalate) copolyester. Water wicking rates into the fabrics were measured by video microscopy from single drops, relevant for point-of-care microfluidic diagnostic devices, and from reservoirs. intra-yarn microchannels in the hydrophilic polyester yarns were shown to selectively transport aqueous fluids, with the flow path governed by the placement of the hydrophilic yarns in the fabric. By comparing fluid transport in fabric constructions with systematic variations in the numbers of adjacent parallel and orthogonal hydrophilic yarns, it was found that inter-yarn microchannels significantly increased wicking rates. Simultaneous wicking of an aqueous and hydrocarbon fluid into the hydrophilic and hydrophobic microchannels of an amphiphilic fabric was successfully demonstrated. The high degree of interfacial contact and micrometer-scale diffusion lengths of such coflowing immiscible fluid streams inside amphiphilic fabrics suggest potential applications as highly scalable and affordable microcontactors for liquid-liquid extractions.     

Solution-phase surface modification in intact poly(dimethylsiloxane) microfluidic channels

An improved approach composed of an oxidation reaction in acidic H2O2 solution and a sequential silanization reaction using neat silane reagents for surface modification of poly(dimethylsiloxane) (PDMS) substrates was developed. This solution-phase approach is simple and convenient for some routine analytical applications in chemistry and biology laboratories and is designed for intact PDMS-based microfluidic devices, with no device postassembly required. Using this improved approach, two different functional groups, poly(ethylene glycol) (PEG) and amine (NH2), were introduced onto PDMS surfaces for passivation of nonspecific protein absorption and attachment of biomolecules, respectively. X-ray electron spectroscopy and temporal contact angle experiments were employed to monitor functional group transformation and dynamic characteristics of the PEG-grafted PDMS substrates; fluorescent protein solutions were introduced into the PEG-grafted PDMS microchannels to test their protein repelling characteristics. These analytical data indicate that the PEG-grafted PDMS surfaces exhibit improved short-term surface dynamics and robust long-term stability. The amino-grafted PDMS microchannels are also relatively stable and can be further activated for modifications with peptide, DNA, and protein on the surfaces of microfluidic channels. The resulting biomolecule-grafted PDMS microchannels can be utilized for cell immobilization and incubation, semiquantitative DNA hybridization, and immunoassay.     

Fabrication of discontinuous surface patterns within microfluidic channels using photodefinable vapor-based polymer coatings

In this report, we introduce a surface modification method for the fabrication of discontinuous surface patterns within microfluidic systems. The method is based on chemical vapor deposition (CVD) of a photodefinable coating, poly(4-benzoyl-p-xylylene-co-p-xylylene), onto the luminal surface of a microfluidic device followed by a photopatterning step to initiate spatially controlled surface binding. During photopatterning, light-reactive groups of the CVD polymer spontaneously react with molecules adjunct to the surface, such as poly(ethylene oxide). We demonstrate the potential of these reactive polymers for surface modification by preventing nonspecific protein adsorption on different substrates including silicon and poly(dimethylsiloxane) as measured by fluorescence microscopy. More importantly, three-dimensional patterns have successfully been created within polymer-based microfluidic channels, establishing spatially controlled, bioinert surfaces. The herein reported surface modification method addresses a critical challenge with respect to surface engineering of microfluidic devices, namely, the fabrication of discontinuous patterns within microchannels.     

利用CO2激光法快速制造PMMA基材的微流控分析芯片

提出一种广泛使用的CO2激光法,以直接读写烧蚀的方式,进行快速的聚甲基丙烯酸甲酯（PMMA）基材的微流控分析芯片的制造.利用此方法所制造的微流道,将以扫描电子显微镜（SEM）、原子力显微镜（AFM）及表面轮廓仪进行各项表面性质的分析.本文所发展的CO2激光烧蚀法,提供了一个可广泛使用及具有经济效应的PMMA基材的微流控分析芯片的制造方法.在此激光制程法中,微流控分析芯片的制造图案可由商业的套装软件绘制而成,再传输至激光系统中进行烧蚀微管道,结果显示利用离焦法的激光制程技术,在没有退火处理的情况下,就可以获得表面相当平滑的微流道,表面粗糙度小于4nm.     

Plastic microfluidic devices modified with polyelectrolyte multilayers

Control of the polymer surface chemistry is a crucial aspect of development of plastic microfluidic devices. When commercially available plastic substrates are used to fabricate microchannels, differences in the EOF mobility from plastic to plastic can be very high. Therefore, we have used polyelectrolyte multilayers (PEMs) to alter the surface of microchannels fabricated in plastics. Optimal modification of the microchannel surfaces was obtained by coating the channels with alternating layers of poly(allylamine hydrochloride) and poly(styrene sulfonate). Polystyrene (PS) and poly(ethylene terephthalate) glycol (PETG) were chosen as substrate materials because of the significant differences in the polymer chemistries and in the EOF of channels fabricated in these two plastic materials. The efficacy of the surface modification has been evaluated using XPS and by measuring the EOF mobility. When microchannels prepared in both PS and PETG are modified with PEMs, they demonstrate very similar electroosmotic mobilities. The PEMs are easily fabricated and provide a means for controlling the flow direction and the electroosmotic mobility in the channels. The PEM-coated microchannels have excellent wettability, allowing facile filling of the channels. In addition, the PEMs produce reproducible results and are robust enough to withstand long-term storage.     

Surface-directed, graft polymerization within microfluidic channels

We demonstrate a simple procedure to coat the surfaces of enclosed PDMS microchannels by UV-mediated graft polymerization. In prior applications, only disassembled channels could be coated by this method. This limited the utility of the method to coatings that could easily and tightly seal with themselves. By preadsorbing a photoinitiator onto the surface of PDMS microchannels, the rate of polymer formation at the surface was greatly accelerated compared to that in solution. Thus, a gel did not form in the lumen of enclosed microchannels. We demonstrate that the photoinitiator benzophenone remained on the surface of PDMS even after extensive washing. After addition of a variety of monomer solutions (acrylic acid, poly(ethylene glycol) monomethoxyl acrylate, or poly(ethylene glycol) diacrylate) and illumination with UV light, a stable, covalently attached surface coating formed in the microchannels. The electroosmotic mobility was stable in response to air exposure and to repeated cycles of hydration-dehydration of the coating. These surfaces also supported the electrophoretic separation of two model analytes. Placement of an opaque mask over a portion of the channel permitted photopatterning of the microchannels with a resolution of approximately 100 microm. By using an appropriate mixture of monomers combined with masks, it should be possible to fabricate PDMS microfluidic devices with distinct surface properties in different regions or channels.     

Simulation of parabolic flow on an eye-shaped domain with moving boundary

During the upstroke of a normal eye blink, the upper lid moves and paints a thin tear film over the exposed corneal and conjunctival surfaces. This thin tear film may be modeled by a nonlinear fourth-order PDE derived from lubrication theory. A challenge in the numerical simulation of this model is to include both the geometry of the eye and the movement of the eyelid. A pair of orthogonal and conformal maps transform a square into an approximate representation of the exposed ocular surface of a human eye. A spectral collocation method on the square produces relatively efficient solutions on the eye-shaped domain via these maps. The method is demonstrated on linear and nonlinear second-order diffusion equations and shown to have excellent accuracy as measured pointwise or by conservation checks. Future work will use the method for thin-film equations on the same type of domain.     

Surface modification of poly(dimethylsiloxane) microfluidic devices by ultraviolet polymer grafting

Poly(dimethylsiloxane) (PDMS)-based microfluidic devices are increasing in popularity due to their ease of fabrication and low costs. Despite this, there is a tremendous need for strategies to rapidly and easily tailor the surface properties of these devices. We demonstrate a one-step procedure to covalently link polymers to the surface of PDMS microchannels by ultraviolet graft polymerization. Acrylic acid, acrylamide, dimethylacrylamide, 2-hydroxylethyl acrylate, and poly(ethylene glycol)monomethoxyl acrylate were grafted onto PDMS to yield hydrophilic surfaces. Water droplets possessed contact angles as low as 45 degrees on the grafted surfaces. Microchannels constructed from the grafted PDMS were readily filled with aqueous solutions in contrast to devices composed of native PDMS. The grafted surfaces also displayed a substantially reduced adsorption of two test peptides compared to that of oxidized PDMS. Microchannels with grafted surfaces exhibited electroosmotic mobilities intermediate to those displayed by native and oxidized PDMS. Unlike the electroosmotic mobility of oxidized PDMS, the electroosmotic mobility of the grafted surfaces remained stable upon exposure to air. The electrophoretic resolution of two test peptides in the grafted microchannels was considerably improved compared to that in microchannels composed of oxidized PDMS. By using the appropriate monomer, it should be possible to use UV grafting to impart a variety of surface properties to PDMS microfluidics devices.     

Fabrication of precise microchannels using a side-insulated tool in a spark assisted chemical engraving process

Microfluidics is an emerging field giving rise to a number of scientific developments with wide applications in proteomics, genomics, DNA analysis, drug delivery systems and lab-on-a-chip. Among the various microfluidic structures, microchannels form an integral part of Lab-on-a-chip devices for clinical diagnosis. The geometrical accuracy and surface finish quality of the microchannels affect the performance of microfluidic systems, thereby demanding a precise microfabrication technique for realizing microchannels. Spark assisted chemical engraving (SACE) is an effective hybrid micromachining technique used for micro-structuring non-conducting substrates such as glass and ceramics. In the present work, we report on a room temperature coated thick insulating film for improving the quality of the microchannels realized using a SACE process. The insulator film coated around a tool electrode confines the spark discharges only to the bottom surface of the tool. Moreover, the proposed insulator coating methodology does not require any cost intensive equipment, carrier gases, vacuum units and a clean room environment. Experimental results demonstrate that for same process parameters a micro-channel fabricated using an insulated tool has its overcut reduced by 57.8% and machining depth improved by 19.53% with a smooth surface and regular edges as compared to the channels realized using an uninsulated tool.     

Room-temperature imprinting method for plastic microchannel fabrication

A new plastic imprinting method using a silicon template is demonstrated. This new approach obviates the necessity of heating the plastic substrate during the stamping process, thus improving the device yield from approximately 10 devices to above 100 devices per template. The dimensions of the imprinted microchannels were found to be very reproducible, with variations of less than 2%. The channel depths were dependent on the pressures applied and the materials used. Rather than bonding the open channels with another piece of plastic, a flexible and adhesive poly(dimethylsiloxane) film is used to seal the microchannels, which offers many advantages. As an application, isoelectric focusing of green fluorescence protein on these plastic microfluidic devices is illustrated.     

Stable microstructured network for protein patterning on a plastic microfluidic channel: strategy and characterization of on-chip enzyme microreactors

Chemical modification of a poly(methyl methacrylate) (PMMA) microchannel surface has been explored to functionalize microfluidic chip systems. A craft copolymer was designed and synthesized to introduce the silane functional groups onto the plastic surface first. Furthermore, it has been found that, through a silicon-oxygen-silicon bridge that formed by tethering to these functional groups, a stable patterning network of gel matrix could be achieved. Thus, anchorage of proteins could be realized onto the hydrophobic PMMA microchannels with bioactivity preserved as far as possible. The protein homogeneous patterning in a microfluidic channel has been demonstrated by performing microchip capillary electrophoresis with laser-induced fluorescence detection and confocal fluorescence microscopy. To investigate the bioactivity of enzymes entrapped within stable silica gel-derived microchannels, the suggested scheme was employed to the construction of immobilized enzyme microreactor-on-a-chip. The proteolytic activity of immobilized trypsin has been demonstrated with the digestion of cytochrome c and bovine serum albumin at a fast flow rate of 4.0 microL/min, which affords the short residence time less than 5 s. The digestion products were characterized using MALDI-TOF MS with sequence coverage of 75 and 31% observed, respectively. This research exhibited a simple but effective strategy of plastic microchip surface modification for protein immobilization in biological and proteomic research.     

Construction of a biomimetic surface on microfluidic chips for biofouling resistance

A biomimetic surface has been formed on the poly(methyl methacrylate) (PMMA) microfluidic chips for biofouling resistance on the basis of a simple modification. Accordingly, an amphiphilic phospholipid copolymer of 2-methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate (PMB) was developed to introduce the phosphorylcholine functional groups onto the PMMA surface via the anchoring of hydrophobic n-butyl methacrylate units. The 2-methacryloyloxyethyl phosphorylcholine segments could form hydrophilic domains, considered to be located on the surface, to provide a biocompatible surface. X-ray photoelectron spectroscopy and Fourier transform infrared spectra confirmed the success of surface functionalization. The PMB-modified microchips containing phosphorylcholine moieties exhibited more stable electroosmotic mobility compared with the untreated one. In addition to being characterized for minimized nonspecific adhesion of serum proteins and plasma platelets, the PMB-functionalized microchannels have been exemplified by electrophoresis of proteins. This one-step procedure offers an effective approach for a biomimetic surface design on microfluidic chips, which is promising in high-throughput and complex biological analysis.     

接触角和质量分数对液滴冻结过程的影响

本文通过Fluent软件的凝固/熔化模型,模拟了接触角及质量分数对纯水和氯化钠溶液在冷表面冻结过程的影响,选择铜片为亲水表面,纳米膜表面为疏水表面,对液滴在不同表面特性条件下的冻结过程进行实验研究.结果表明:液滴在冷表面的冻结特性与接触角、质量分数有关.当溶液质量分数一定时,接触角越小,液滴冻结速度越快,完全冻结时间越...     

Surface characterization of laser-ablated polymers used for microfluidics

Fabrication of microfluidic devices by excimer laser ablation under different atmospheres may provide variations in polymer microchannel surface characteristics. The surface chemistry and electroosmotic (EO) mobility of polymer microchannels laser ablated under different atmospheres were studied by X-ray photoelectron spectroscopy and current monitoring mobility measurements, respectively. The ablated surfaces of PMMA were very similar to the native material, regardless of ablation atmospheres due to the negligible absorption of 248-nm light by that polymer. The substrates studied that exhibit nonnegligible absorption at this energy, namely, poly(ethylene terephthalate glycol), poly(vinyl chloride), and poly(carbonate), showed significant changes in surface chemistry and EO mobility when the ablation atmospheres were varied. Ablation of these three polymer substrates under nitrogen or argon resulted in low EO mobilities with a loss of the well-defined chemical structures of the native surfaces, while ablation under oxygen yielded surfaces that retained native chemical structures and supported higher EO mobilities.     

Low-Cost Customized Color-Blind Contact Lenses using 3D Printed Molds

Prominence of color perception in our day-to-day routine is unequivocally pronounced, yet visual ramifications due to color vision deficiency (CVD) or color blindness impede carriers of this disorder from functioning normally. To circumvent this deficiency, patients opt for tinted glasses/contact lenses to complement their color distinction capabilities. Red-green color blindness, the most prevalent form of CVD, can be alleviated using such glasses/lenses that filter out problematic wavelengths (540–580 nm). Nonetheless, nearly all contact lenses established by companies and developed by researchers are tinted throughout their entire surface, causing patients discomfort and needless attention as people can easily note their deficiency. Ideally, the tint within the lens should only cover the eye's pupil as it is responsible for perceiving light. Hence herein, CVD contact lenses are fabricated by solely tinting the midportion of commercial lenses utilizing two additively manufactured molds with 4 and 8 mm-diameter holes to emulate the humans’ average pupil size. The tinted lenses filter light effectively at 530–590 nm with their transmission dip being at 558 nm. The contact lenses show excellent wettability and water retention capabilities along with demonstrating superior wavelength-filtering properties to most of the commercial and research-based CVD wearables.     

Application of fluorescence correlation spectroscopy for velocity imaging in microfluidic devices

In this paper we present and demonstrate a technique for mapping fluid flow rates in microfluidic systems with sub-micrometer resolution using confocal microscopy in conjunction with fluorescence correlation spectroscopy (FCS). Flow velocities ranging from approximately 50 microm/s to approximately 10 cm/s can be recorded using fluorescent polymer nanospheres as fluid motion tracers. Velocity profiles and images of the flow in poly(dimethylsiloxane)-glass microchannels are presented and analyzed. Using the method, velocity images along the horizontal (top view) and vertical planes within a microdevice can be obtained. This is, to our knowledge, the first report of FCS for producing velocity maps. The high-resolution velocity maps can be used to characterize and optimize microdevice performance and to validate simulation efforts.     

Human tear protein analysis enabled by an alkaline microfluidic homogeneous immunoassay

The ability to probe the protein content of human tear fluid has enormous potential for deepening our understanding of ocular and systemic disease pathology and enabling novel noninvasive tear-based diagnostic technologies. To overcome current challenges in tear proteomic measurements, we report on the first microfluidic homogeneous immunoassay capable of making rapid, quantitative, and specific measurements of endogenous tear protein biomarkers in human tear fluid. Lactoferrin (Lf) is a tear-specific biomarker for Sj?gren's syndrome (SS), a serious systemic autoimmune disease currently diagnosed through rudimentary volumetric and surface chemistry measurements and an invasive lip biopsy. We detail optimization of a homogeneous electrophoretic immunoassay for Lf in <1 μL of tear fluid at clinically relevant concentrations. In particular, we present assay development details and a final assay that enables quantification of Lf in <5 s in a clinically relevant range for SS diagnostics. Characterization suggests the on-chip assay is accurate to within 15% of ELISA, specific (<15% nonspecific signal), and with a lower limit of detection of 3 ± 2 nM Lf in human tear matrix. Additionally, we develop and characterize a protocol for eluting proteins from nitrocellulose Schirmer strips, the clinical de facto standard for tear collection and storage. We relate on-chip measured Lf concentrations back to ocular surface concentrations for the first time to our knowledge. Taken in sum, this work details important steps toward (1) expanding the set of proteins quantified by electrophoretic immunoassays to encompass a wider range of isoelectric points than has been reported, (2) creating a first-in-kind translatable assay with clinical relevance to SS diagnostics, and (3) expanding the analytical toolkit available for rapid tear protein measurements, as is relevant to the advancement of basic research and clinical medicine.     

A soft lithographic approach to fabricate patterned microfluidic channels

The control of surface properties and spatial presentation of functional molecules within a microfluidic channel is important for the development of diagnostic assays and microreactors and for performing fundamental studies of cell biology and fluid mechanics. Here, we present a simple technique, applicable to many soft lithographic methods, to fabricate robust microchannels with precise control over the spatial properties of the substrate. In this approach, the patterned regions were protected from oxygen plasma by controlling the dimensions of the poly(dimethylsiloxane) (PDMS) stamp and by leaving the stamp in place during the plasma treatment process. The PDMS stamp was then removed, and the microfluidic mold was irreversibly bonded to the substrate. The approach was used to pattern a nonbiofouling poly(ethylene glycol)-based copolymer or the polysaccharide hyaluronic acid within microfluidic channels. These nonbiofouling patterns were then used to fabricate arrays of fibronectin and bovine serum albumin as well as mammalian cells. In addition, further control over the deposition of multiple proteins onto multiple or individual patterns was achieved using laminar flow. Also, cells that were patterned within channels remained viable and capable of performing intracellular reactions and could be potentially lysed for analysis.     

食品工业清洗剂在含水工况下对点接触润滑和摩擦的影响

本文采用工业常用的两性表面活性剂作为润滑油中的添加剂,研究其对点接触润滑和摩擦性能的影响。试验研究结果表明:钢球-玻璃盘润滑实验表明较低浓度的活性剂水溶液对润滑油膜厚度的影响较小,其油膜厚度与纯油润滑基本一致。钢球-蓝宝石相对滑动过程中发现较高的活性剂水溶液浓度下,能够观察到蓝宝石盘会将清洗液带入接触区。钢球-钢盘摩擦磨损工况下活性剂对接触表面有一定的防护作用。