3D printed microfluidic lab-on-a-chip device for fiber-based dual beam optical manipulation

Abstract3D printing of microfluidic lab-on-a-chip devices enables rapid prototyping of robust and complex structures. In this work, we designed and fabricated a 3D printed lab-on-a-chip device for fiber-based dual beam optical manipulation. The final 3D printed chip offers three key features, such as (1) an optimized fiber channel design for precise alignment of optical fibers, (2) an optically clear window to visualize the trapping region, and (3) a sample channel which facilitates hydrodynamic focusing of samples. A square zig–zag structure incorporated in the sample channel increases the number of particles at the trapping site and focuses the cells and particles during experiments when operating the chip at low Reynolds number. To evaluate the performance of the device for optical manipulation, we implemented on-chip, fiber-based optical trapping of different-sized microscopic particles and performed trap stiffness measurements. In addition, optical stretching of MCF-7 cells was successfully accomplished for the purpose of studying the effects of a cytochalasin metabolite, pyrichalasin H, on cell elasticity. We observed distinct changes in the deformability of single cells treated with pyrichalasin H compared to untreated cells. These results demonstrate that 3D printed microfluidic lab-on-a-chip devices offer a cost-effective and customizable platform for applications in optical manipulation.

Strategy for fast manufacturing of 3D hydrodynamic focusing multilayer microfluidic chips and its application for flow-based synthesis of gold nanoparticles

Fabrication of 3D microfluidic devices is normally quite expensive and tedious. A strategy was established to rapidly and effectively produce multilayer 3D microfluidic chips which are made of two layers of poly(methyl methacrylate) (PMMA) sheets and three layers of double-sided pressure sensitive adhesive (PSA) tapes. The channel structures were cut in each layer by cutting plotter before assembly. The structured channels were covered by a PMMA sheet on top and a PMMA carrier which contained threads to connect with tubing. A large variety of PMMA slides and PSA tapes can easily be designed and cut with the help of a cutting plotter. The microfluidic chip was manually assembled by a simple lamination process.The complete fabrication process from device design concept to working device can be completed in minutes without the need of expensive equipment such as laser, thermal lamination, and cleanroom. This rapid frabrication method was applied for design of a 3D hydrodynamic focusing device for synthesis of gold nanoparticles (AuNPs) as proof-of-concept. The fouling of AuNPs was prevented by means of a sheath flow. Different parameters such as flow rate and concentration of reagents were controlled to achieve AuNPs of various sizes. The sheet-based fabrication method offers a possibility to create complex microfluidic devices in a rapid, cheap and easy way.

Millisecond timescale reactions observed via X-ray spectroscopy in a 3D microfabricated fused silica mixer

Determination of electronic structures during chemical reactions remains challenging in studies which involve reactions in the millisecond timescale, toxic chemicals, and/or anaerobic conditions. In this study, a three-dimensionally (3D) microfabricated microfluidic mixer platform that is compatible with time-resolved X-ray absorption and emission spectroscopy (XAS and XES, respectively) is presented. This platform, to initiate reactions and study their progression, mixes a high flow rate (0.50–1.5 ml min−1) sheath stream with a low-flow-rate (5–90 µl min−1) sample stream within a monolithic fused silica chip. The chip geometry enables hydrodynamic focusing of the sample stream in 3D and sample widths as small as 5 µm. The chip is also connected to a polyimide capillary downstream to enable sample stream deceleration, expansion, and X-ray detection. In this capillary, sample widths of 50 µm are demonstrated. Further, convection–diffusion-reaction models of the mixer are presented. The models are experimentally validated using confocal epifluorescence microscopy and XAS/XES measurements of a ferricyanide and ascorbic acid reaction. The models additionally enable prediction of the residence time and residence time uncertainty of reactive species as well as mixing times. Residence times (from initiation of mixing to the point of X-ray detection) during sample stream expansion as small as 2.1 ± 0.3 ms are also demonstrated. Importantly, an exploration of the mixer operational space reveals a theoretical minimum mixing time of 0.91 ms. The proposed platform is applicable to the determination of the electronic structure of conventionally inaccessible reaction intermediates.

Excipient-Free Pure Drug Nanoparticles Fabricated by Microfluidic Hydrodynamic Focusing

Nanoprecipitation is one of the most versatile methods to produce pure drug nanoparticles (PDNPs) owing to the ability to optimize the properties of the product. Nevertheless, nanoprecipitation may result in broad particle size distribution, low physical stability, and batch-to-batch variability. Microfluidics has emerged as a powerful tool to produce PDNPs in a simple, reproducible, and cost-effective manner with excellent control over the nanoparticle size. In this work, we designed and fabricated T- and Y-shaped Si-made microfluidic devices and used them to produce PDNPs of three kinase inhibitors of different lipophilicity and water-solubility, namely imatinib, dasatinib and tofacitinib, without the use of colloidal stabilizers. PDNPs display hydrodynamic diameter in the 90–350 nm range as measured by dynamic light scattering and a rounded shape as visualized by high-resolution scanning electron microscopy. Powder X-ray diffraction and differential scanning calorimetry confirmed that this method results in highly amorphous nanoparticles. In addition, we show that the flow rate of solvent, the anti-solvent, and the channel geometry of the device play a key role governing the nanoparticle size.

Micro Milling Process for the Rapid Prototyping of Microfluidic Devices

Micro milling process has become an attractive method for the rapid prototyping of micro devices. The process is based on subtractive manufacturing method in which materials from a sample are removed selectively. A comprehensive review on the fabrication of circular and rectangular cross-section channels of microfluidic devices using micro milling process is provided this review work. Process and machining parameters such as micro-tools selection, spindle speed, depth of cut, feed rate and strategy for process optimization will be reviewed. A case study on the rapid fabrication of a rectangular cross section channel of a microflow cytometer device with 200 um channel width and 50 um channel depth using CNC micro milling process is provided. The experimental work has produced a low surface roughness micro channel of 20 nm in roughness and demonstrated a microflow cytometer device that can produce hydrodynamic focusing with a focusing width of about 60 um.

Integration of 3D Hydrodynamic Focused Microreactor with Microfluidic Chemiluminescence Sensing for Online Synthesis and Catalytical Characterization of Gold Nanoparticles

Chemiluminescence assays have shown great advantages compared with other optical techniques. Gold nanoparticles have drawn much attention in chemiluminescence analysis systems as an enzyme-free catalyst. The catalytic activity of gold nanoparticles for chemiluminescence sensing depends on size, shape and the surface charge property, which is hard to characterize in batches. As there is no positive or negative correlation between chemiluminescence signals and sizes of gold nanoparticles, the best way to get optimal gold nanoparticles is to control the reaction conditions via online chemiluminescence sensing systems. Therefore, a new method was developed for online synthesis of gold nanoparticles with a three-dimension hydrodynamic focusing microreactor, directly coupled with a microfluidic chemiluminescence sensing chip, which was coupled to a charge-coupled device camera for direct catalytical characterization of gold nanoparticles. All operations were performed in an automatic way with a program controlled by Matlab. Gold nanoparticles were synthesized through a single-phase reaction using glucose as a reducing agent and stabilizer at room temperature. The property of gold nanoparticles was easily controlled with the three-dimension microreactor during synthesis. The catalyst property of synthesized gold nanoparticles was characterized in a luminol–NaOCl chemiluminescence system. After optimizing parameters of synthesis, the chemiluminescence signal was enhanced to a factor of 171. The gold nanoparticles synthesized under optimal conditions for the luminol–NaOCl system were stable for at least one month. To further investigate the catalytic activity of synthesized gold nanoparticles in various situations, two methods were used to change the property of gold nanoparticles. After adding a certain amount of salt (NaCl), gold nanoparticles aggregated with a changed surface charge property and the catalytic activity was greatly enhanced. Glutathione was used as an example of molecules with thiol groups which interact with gold nanoparticles and reduce the catalytic activity. The chemiluminescence intensity was reduced by 98.9%. Therefore, we could show that using a microreactor for gold nanoparticles synthesis and direct coupling with microfluidic chemiluminescence sensing offers a promising monitoring method to find the best synthesis condition of gold nanoparticles for catalytic activity.

On secondary atomization and blockage of surrogate cough droplets in single- and multilayer face masks

Face masks prevent transmission of infectious respiratory diseases by blocking large droplets and aerosols during exhalation or inhalation. While three-layer masks are generally advised, many commonly available or makeshift masks contain single or double layers. Using carefully designed experiments involving high-speed imaging along with physics-based analysis, we show that high-momentum, large-sized (>250 micrometer) surrogate cough droplets can penetrate single- or double-layer mask material to a significant extent. The penetrated droplets can atomize into numerous much smaller (<100 micrometer) droplets, which could remain airborne for a significant time. The possibility of secondary atomization of high-momentum cough droplets by hydrodynamic focusing and extrusion through the microscale pores in the fibrous network of the single/double-layer mask material needs to be considered in determining mask efficacy. Three-layer masks can effectively block these droplets and thus could be ubiquitously used as a key tool against COVID-19 or similar respiratory diseases.