An Alternative Micro-Milling Fabrication Process for Rapid and Low-Cost Microfluidics.

Microfluidics is an important technology for the biomedical industry and is often utilised in our daily lives. Recent advances in micro-milling technology have allowed for rapid fabrication of smaller and more complex structures, at lower costs, making it a viable alternative to other fabrication methods. The microfluidic chip fabrication developed in this research is a step-by-step process with a self-contained wet milling chamber. Additionally, ethanol solvent bonding is used to allow microfluidic chips to be fully fabricated within approximately an hour. The effect of using this process is tested with quantitative contact profileometery data to determine the expected surface roughness in the microchannels. The effect of surface roughness on the controllability of microparticles is tested in functional microfluidic chips using image processing to calculate particle velocity. This process can produce high-quality channels when compared with similar studies in the literature and surface roughness affects the control of microparticles. Lastly, we discuss how the outcomes of this research can produce rapid and higher-quality microfluidic devices, leading to improvement in the research and development process within the fields of science that utilise microfluidic technology. Such as medicine, biology, chemistry, ecology, and aerospace.

Precision-milled simulated curved root canals in bovine dentine for the assessment of chemo-mechanical root canal preparation.

AIM: The aim was to develop a standardized curved root canal model in bovine dentine and to assess whether that natural substrate would behave differently from the resin in standard plastic training blocks when prepared chemo-mechanically. The impact of substrate microhardness on simulated canal transportation was considered. METHODOLOGY: High-precision computer numerical control (CNC) milling was used to recreate a simulated root canal from a resin training block (Endo Training Bloc J-Shape, size 15) in longitudinally sectioned, dis- and re-assembled bovine incisor roots. Optical overlays obtained from 10 resin blocks were used to identify an average canal and program the CNC milling apparatus accordingly. Resin and dentine microhardness were measured. Simulated root canals in resin training blocks and their bovine counterparts were then instrumented at 37°C using Reciproc R25 instruments (VDW) with water or 17% EDTA (n = 10). Open-access image processing software was used to superimpose and analyse pre- and postoperative images obtained with a digital microscope. Centering ratios were averaged to indicate canal transportation. The effects of substrate and irrigant on canal transportation were assessed by two-way anova. RESULTS: Superimposed images showed that resin blocks under investigation varied considerably in terms of simulated canal length and curvature, whilst the milled canals were highly similar. The microhardness of dentine was more than three times higher than that of the resin. Conversely, canal transportation was considerably greater in dentine compared to resin, and in dentine had a tendency to be increased by EDTA. There was a strong effect of substrate on canal transportation (p < .001), no overall effect of irrigant, and a marginally significant interaction between irrigant and substrate (p = .077). CONCLUSIONS: CNC milling allows to create standardized simulated curved root canals in bovine dentine. These models may be useful to test and compare materials and concepts of chemo-mechanical root canal instrumentation. Microhardness is a bulk feature that does not predict the response to chemo-mechanical instrumentation of a composite material such as dentine.

Computer numerical control (CNC) carving as an on-demand point-of-care manufacturing of solid dosage form: A digital alternative method for 3D printing.

Computer numerical control (CNC) carving is a widely used method of industrial subtractive manufacturing of wood, plastics, and metal products. However, there have been no previous reports of applying this approach to manufacture medicines. In this work, the novel method of tablet production using CNC carving is introduced for the first time. This report provides a proof-of-concept for applying subtractive manufacturing as an alternative to formative (powder compression) and additive (3D printing) manufacturing for the on-demand production of solid dosage forms. This exemplar manufacturing approach was employed to produce patient-specific hydrocortisone (HC) tablets for the treatment of children with congenital adrenal hyperplasia. A specially made drug-polymer cast based on polyethene glycol (PEG 6,000) and hydroxypropyl cellulose was produced using thermal casting. The cast was used as a workpiece and digitally carved using a small-scale 3-dimensional (3D) CNC carving. To establish the ability of this new approach to provide an accurate dose of HC, four different sizes of CNC carved tablet were manufactured to achieve HC doses of 2.5, 5, 7.5 and 10 mg with a relative standard deviation of the tablet weight in the range of 3.69-4.79%. In addition, batches of 2.5 and 5 mg HC tablets met the British Pharmacopeia standards for weight uniformity. Thermal analysis and X-ray powder diffraction indicated that the model drug was in amorphous form. In addition, HPLC analysis indicated a level of purity of 96.5 ± 1.1% of HC. In addition, the process yielded mechanically strong cylindrical tablets with tensile strength ranging from 0.49 to 1.6 MPa and friability values of <1%, whilst maintaining an aesthetic look. In vitro, HC release from the CNC-carved tablets was slower with larger tablet sizes and higher binder contents. This is the first report on applying CNC carving in the pharmaceutical context of producing solid dosage forms. The work showed the potential of this technology as an alternative method for the on-demand manufacturing of patient-specific dosage forms.

Comparative Study about Dimensional Accuracy and Surface Finish of Constant-Breadth Cams Manufactured by FFF and CNC Milling.

In this work, the design, manufacture and measurement process of constant-breadth cams is presented. The motion law of the cam was designed by means of Bézier curves and the corresponding design desmodromic constraints. The cams were manufactured in two different materials employing two different processes: PLA cams with fused filament fabrication (FFF) and aluminium cams with computer numerical control (CNC) milling. The main aim of this work is to compare both types of cams regarding dimensional accuracy and surface finish, in order to evaluate if it would be possible to temporally replace a metallic cam with a plastic one during the repair of the first one. Dimensions were measured with micrometres and surface roughness with a contact roughness meter. The results show that, in diametral dimensions, similar dimensional error values were obtained for both the 3D-printed and the machined cams. However, in longitudinal dimensions, whose direction is perpendicular to the 3D-printed layers, the 3D-printed cams showed higher dimensional error than the machined ones. The average roughness Ra in the 3D-printed cams was 20 times higher than in the milled cams. According to the results, it would be recommended to temporally replace metallic cams with plastic ones in applications of low-power transmission. Given that in the literature little information is available about the measurement of 3D-printed desmodromic cams, this work will contribute to the study and analysis of this kind of 3D printed mechanism.

Fabrication of Concave Microwells and Their Applications in Micro-Tissue Engineering: A Review.

At present, there is an increasing need to mimic the in vivo micro-environment in the culture of cells and tissues in micro-tissue engineering. Concave microwells are becoming increasingly popular since they can provide a micro-environment that is closer to the in vivo environment compared to traditional microwells, which can facilitate the culture of cells and tissues. Here, we will summarize the fabrication methods of concave microwells, as well as their applications in micro-tissue engineering. The fabrication methods of concave microwells include traditional methods, such as lithography and etching, thermal reflow of photoresist, laser ablation, precision-computerized numerical control (CNC) milling, and emerging technologies, such as surface tension methods, the deformation of soft membranes, 3D printing, the molding of microbeads, air bubbles, and frozen droplets. The fabrication of concave microwells is transferring from professional microfabrication labs to common biochemical labs to facilitate their applications and provide convenience for users. Concave microwells have mostly been used in organ-on-a-chip models, including the formation and culture of 3D cell aggregates (spheroids, organoids, and embryoids). Researchers have also used microwells to study the influence of substrate topology on cellular behaviors. We will briefly review their applications in different aspects of micro-tissue engineering and discuss the further applications of concave microwells. We believe that building multiorgan-on-a-chip by 3D cell aggregates of different cell lines will be a popular application of concave microwells, while integrating physiologically relevant molecular analyses with the 3D culture platform will be another popular application in the near future. Furthermore, 3D cell aggregates from these biosystems will find more applications in drug screening and xenogeneic implantation.

Stress Distribution on Various Implant-Retained Bar Overdentures.

The purpose of this study was to evaluate the effects of various fabrication techniques and materials used in implant-supported mandibular overdentures with a Hader bar attachment over added stress distribution. Three-dimensional geometric solid models, consisting of two implants (3.3 mm × 12 mm) placed at the bone level on both mandibular canine regions and a Hader bar structure, were prepared. Model 1 simulated a bar retentive system made from Titanium Grade 5 material by Computer Numerical Control (CNC) milling technique without using any converting adapter/multi-unit element on the implants, while Model 2 simulated the same configuration, but with converting adapters on the implants. Model 3 simulated a bar retentive system made from Cobalt-Chromium material, made by using conventional casting technique with converting adapters on the implants. Static loads of 100 Newton were applied on test models from horizontal, vertical and oblique directions. ANSYS R15.0 Workbench Software was used to compare Von Mises stress distribution and minimum/maximum principal stress values, and the results were evaluated by using Finite Element Analysis method. As a result, the highest stress distribution values under static loading in three different directions were obtained in Model 1. Stress was observed intensely around the necks of the implants and the surrounding cortical bone areas in all models. In scope of the results obtained, using converting adapters on implants has been considered to decrease transmission of forces onto implants and surrounding bone structures, thus providing a better stress distribution. It has also been observed that the type of material used for bar fabrication has no significant influence on stress values in those models where converting adapters were used.

A Low-Cost 3-in-1 3D Printer as a Tool for the Fabrication of Flow-Through Channels of Microfluidic Systems.

Recently published studies have shown that microfluidic devices fabricated by in-house three-dimensional (3D) printing, computer numerical control (CNC) milling and laser engraving have a good quality of performance. The 3-in-1 3D printers, desktop machines that integrate the three primary functions in a single user-friendly set-up are now available for computer-controlled adaptable surface processing, for less than USD 1000. Here, we demonstrate that 3-in-1 3D printer-based micromachining is an effective strategy for creating microfluidic devices and an easier and more economical alternative to, for instance, conventional photolithography. Our aim was to produce plastic microfluidic chips with engraved microchannel structures or micro-structured plastic molds for casting polydimethylsiloxane (PDMS) chips with microchannel imprints. The reproducability and accuracy of fabrication of microfluidic chips with straight, crossed line and Y-shaped microchannel designs were assessed and their microfluidic performance checked by liquid stream tests. All three fabrication methods of the 3-in-1 3D printer produced functional microchannel devices with adequate solution flow. Accordingly, 3-in-1 3D printers are recommended as cheap, accessible and user-friendly tools that can be operated with minimal training and little starting knowledge to successfully fabricate basic microfluidic devices that are suitable for educational work or rapid prototyping.

Sound Detection Monitoring Tool in CNC Milling Sounds by K-Means Clustering Algorithm.

Computer numerical control (CNC) is a machine used in the manufacturing industry to produce components quickly for the engineering field or the desired shape. In the milling process carried out by CNC machines, sometimes vibrations occur that cause unwanted cracks or damage, which if left unchecked, will cause more severe damage. For this reason, this study describes how to monitor and analyze the sound produced by CNC during the milling process. This study uses six sound sample videos from YouTube, and there are two modes: (1) the operating mode is three different shapes with XY, XZ, and XYZ axes, and the second (2) is based on material differences. Namely, wood, Styrofoam, and plastic. The sound generated from all samples of the CNC milling processes will be detected using a sound detection program that has been designed in the LabVIEW using a simple microphone. The resulting sound frequency will be analyzed using the fast Fourier transform (FFT) process in spectral measurements, which will produce the amplitude and frequency of the detected sound in real time in the form of a graph. All frequency results that have been obtained from the sound detection monitoring tool in the CNC milling machine will be imported into the K-means clustering algorithm where the different frequencies between the resonant frequency and noise will be classified. Based on the experiments conducted, the sound detection program can detect sounds with a significant level of sensitivity.

Advanced design and manufacturing of custom orthotics insoles based on hybrid Taguchi-response surface method.

Herein, a machining strategy to fabricate custom orthotic insoles with high surface finish and wide fit tolerance is presented. CNC milling was used to machine ethylene-vinyl acetate (EVA) foam for insoles with various surface hardness, and the Taguchi-response surface method (TM-RSM) was adopted to optimize the parameters of the CNC milling process (cutting speed, feed rate, tool path strategy, and step over). EVA foam with varying surface hardness and the tolerance of the wide fit insoles corresponding to the surface roughness were analyzed. Subsequently, a mathematical model was established to determine the optimal CNC milling parameters for a standard milling cutter under dry coolants. The results of the six parameters corresponding to the mean values of surface roughness were initially examined using the signal-to-noise ratio of the Taguchi method (TM). The surface roughness obtained with the TM-RSM was up to 4.13% higher than that obtained with the TM. The EVA foam insole with a surface hardness of 50-60 HRC and a wide fit tolerance of 0.75 mm provided the ideal level of comfort and support for patients with diabetes. The results of this study demonstrated that CNC milling provided a better surface finish of orthotic shoe insoles than other methods, which can serve as guidance in the development of machining strategies for insoles made from EVA foam.

Accuracy of implant surgical guides fabricated using computer numerical control milling for edentulous jaws: a pilot clinical trial.

BACKGROUND: To evaluate the accuracy of a computer numerical control (CNC) milled surgical guide for implant placement in edentulous jaws. METHODS: Edentulous patients seeking implants treatment were recruited in this prospective cohort study. Radiographic guides with diagnostic templates were fabricated from wax-up dentures. Patients took cone-beam computed tomography (CBCT) wearing the radiopaque radiographic guides. Implant positions were virtually designed in the planning software based on the CBCT data, and the radiographic templates were converted into surgical guides using CNC milling technique. Forty-four implants were placed into 12 edentulous jaws following guided implant surgery protocol. Post-surgery CBCT scans were made for each jaw, and the deviations between the planned and actual implant positions were measured. Deviation of implant position was compared between maxilla and mandible, and between cases with and without anchor pins using independent t-test. RESULTS: Nine patients (3 males and 6 females) with 12 edentulous jaws were recruited. The mean age of patients was 59.2 ± 13.9 years old. All 44 implants was placed without complication and survived, the mean three dimensional linear deviation of implant position between virtual planning and actual placement was 1.53 ± 0.48 mm at the implant neck and 1.58 ± 0.49 mm at the apex. The angular deviation was 3.96 ± 3.05 degrees. No significant difference was found in the deviation of implant position between maxilla and mandible (P = 0.28 at neck, 0.08 at apex), nor between cases with and without anchor pins (P = 0.87 at neck, 0.06 at apex). CONCLUSIONS: The guides fabricated using the CNC milling technique provided comparable accuracy as those fabricated by Stereolithography. The displacement of the guides on edentulous arch might be the main contributing factor of deviation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-ONC-17014159 (July 26, 2017).

Accuracy of CAD/CAM-fabricated bite splints: milling vs 3D printing.

OBJECTIVES: The aim of this study was to investigate the accuracy of CAD/CAM-fabricated bite splints in dependence of fabrication method (milling vs 3D printing), positioning (horizontal vs vertical), selection of material, and method of deviation measurement. MATERIALS AND METHODS: Bite splints were 3D-printed in either horizontal or vertical position (n = 10) using four different resins (Dental LT, Ortho Clear, Freeprint Splint, V-Splint). As control, ten bite splints were fabricated by CNC milling (ProArt CAD Splint). The splints were scanned and deviations between the CAD-file (trueness) and between each other within one group (precision) were measured by two different software applications and methods (cloud-to-cloud vs cloud-to-mesh). Data were analyzed using univariate analysis, Kolmogorov-Smirnov, Kruskal-Wallis, and Mann-Whitney U tests. RESULTS: The highest impact on accuracy was exerted by the selection of the material (trueness: ηP2 = 0.871, P < 0.001; precision: ηP2 = 0.715, P < 0.001). Milled splints showed the highest trueness (P < 0.01) but not the highest precision at the same time. Horizontally positioned 3D-printed bite splints showed the least deviations in terms of trueness while vertical positioning resulted in the highest precision. The cloud-to-cloud method showed higher measured deviations than the other methods (P < 0.001-P = 0.002). CONCLUSION: Milled splints show higher trueness than 3D-printed ones, while the latter reveal higher reproducibility. The calculated deviations vary according to the measurement method used. CLINICAL RELEVANCE: In terms of accuracy, milled and 3D-printed bite splints seem to be of equal quality.

CNC-Milled Superhydrophobic Macroporous Monoliths for 3D Cell Culture.

High-strength macroporous monoliths can be obtained by the simple mixing of boehmite nanofiber aqueous acetate dispersions with methyltrimethoxysilane. On the boehmite nanofiber-polymethylsilsesquioxane monoliths, we can fabricate structures smaller than a millimeter in size by computer numerical control (CNC) milling, resulting in a machined surface that is superhydrophobic and biocompatible. Using this strategy, we fabricated a superhydrophobic multiwell plate that holds water droplets to produce 3D cell culture environments for various cell types. We expect these superhydrophobic monoliths to have future applications in 3D tissue construction.

Shake-it-off: a simple ultrasonic cryo-EM specimen-preparation device.

Although microscopes and image-analysis software for electron cryomicroscopy (cryo-EM) have improved dramatically in recent years, specimen-preparation methods have lagged behind. Most strategies still rely on blotting microscope grids with paper to produce a thin film of solution suitable for vitrification. This approach loses more than 99.9% of the applied sample and requires several seconds, leading to problematic air-water interface interactions for macromolecules in the resulting thin film of solution and complicating time-resolved studies. Recently developed self-wicking EM grids allow the use of small volumes of sample, with nanowires on the grid bars removing excess solution to produce a thin film within tens of milliseconds from sample application to freezing. Here, a simple cryo-EM specimen-preparation device that uses components from an ultrasonic humidifier to transfer protein solution onto a self-wicking EM grid is presented. The device is controlled by a Raspberry Pi single-board computer and all components are either widely available or can be manufactured by online services, allowing the device to be constructed in laboratories that specialize in cryo-EM rather than instrument design. The simple open-source design permits the straightforward customization of the instrument for specialized experiments.

Simulations and error analysis of the CNC milling of a face gear tooth with given tool paths.

This data article gives the validation files to the article "CNC milling of face gears with a novel geometric analysis" [1]. The data is about the simulation and machining error analysis of the CNC milling of a face gear tooth with given tool paths. It includes four files. Three of them are simulation videos of the CNC milling process in VERICUT with a general view, partial view and enlarged view, respectively. The other one is the source file of the machining error analysis, and it has the design model of the face gear, the simulated machined model of the face gear, and machining error analysis according to the comparison of the design model and simulated machined model.

Versatile reconfigurable glass capillary microfluidic devices with Lego® inspired blocks for drop generation and micromixing.

Novel cost effective, versatile, reconfigurable, reusable and easy to assemble glass capillary microfluidic devices were developed and used to generate micro/nano-materials with controlled size and morphology. The devices are composed of coaxial assemblies of glass capillaries held between two interchangeable plastic blocks fabricated from chemically inert polyoxymethylene copolymer using computer numerical control (CNC) machining. Three different blocks were combined and locked together using Lego® inspired stud-and-hole coupling system to achieve different flow configurations. The device allows a truly axisymmetric round capillary inside a round capillary geometry and self-alignment of capillaries. The synthesis of polyvinylpyrrolidone capped gold nanoparticles and liposomes of controlled size was demonstrated in the co-flow device by mixing the contents of two parallel laminar streams. The flow focusing device was used to generate piroxicam monohydrate crystals of controlled size (10-29 µm) by antisolvent crystallisation. Silver nanoparticles with tailored size (40-90 nm) were prepared in the three-phase device by merging silver nitrate and tannic acid/citrate streams inside droplets. The same device was used to prepare fluorescently labelled double emulsion droplets with controlled number of inner droplets. The droplet morphology was modified and tuned during operation by adjusting the distance between the inner capillaries. Water-in-oil emulsions consisted of Eudragit S100 solution at pH > 7 dispersed in Miglyol® 840 were prepared and gellified in situ over 6 h without fouling. The setup time of the novel devices was reduced from ∼30 min in manually made capillary devices to just several minutes.

Evaluation of coloured materials in microfluidic flow-cells for chemiluminescence detection.

Recent advances in the construction of chemiluminescence flow-cells has included high precision milling of channels into a range of different polymer materials, in efforts to maximise the transfer of light from the chemical reaction to the photodetector. However, little is known of the extent that the colour of polymer materials will influence this transfer. This may become increasingly important as chemiluminescence detection zones are integrated with other operations within microfluidic devices or micro total analysis systems (µTAS). Herein, we compare microfluidic flow-cells fabricated from five polymer sheets (clear, white, black, red, blue), using two flow-cell designs (spiral and serpentine), two modes of photodetection, and four chemiluminescence reactions that provide a range of different emission colours. The direct transfer of light from the reaction within the white flow-cell channel to the photodetector made only minor contributions (10%-20%) to the measured intensity, with the majority of the measured light first interacting with the polymer material into which the channels were machined. The extent that the emitted light was absorbed or reflected by the coloured polymer materials was dependent on not only the properties of the polymer, but also the spectral distribution of the chemiluminescence. The changes in chemiluminescence intensities from absorption of light by the flow-cell materials can be accompanied by distortion of the spectral distribution.

3D-printed and CNC milled flow-cells for chemiluminescence detection.

Herein we explore modern fabrication techniques for the development of chemiluminescence detection flow-cells with features not attainable using the traditional coiled tubing approach. This includes the first 3D-printed chemiluminescence flow-cells, and a milled flow-cell designed to split the analyte stream into two separate detection zones within the same polymer chip. The flow-cells are compared to conventional detection systems using flow injection analysis (FIA) and high performance liquid chromatography (HPLC), with the fast chemiluminescence reactions of an acidic potassium permanganate reagent with morphine and a series of adrenergic phenolic amines.