The fabrication of microfluidic devices has progressed from cleanroom manufacturing to replica molding in polymers, and more recently to direct manufacturing by subtractive (e.g., laser machining) and additive (e.g., 3D...

High-resolution low-cost LCD 3D printing for microfluidic and organ-on-a-chip devices

Lab-on-a-chip or LOC is a term that is used to describe microfluidic devices that integrate multiple analyte detection, which are normally carried out in a laboratory, into one micro-chip unit and may have applications in diverse fields such as electronics, medicine and biomedical domains. Even though microfluidics has advanced greatly during the past decade due to increased needs for portability, reduced sample requirement and multiple analyte detection capabilities biological research has not adopted the technology at the required pace. This may be owing to the time-consuming and expensive process involved in the microfabrication of biochips, the requirement of specialised setup facilities and the extremely high cost associated with microfluidics as compared to conventional technologies. In recent years, three-dimensional (3D) printing has piqued curiosity in the scientific community. It has the potential to create complex, high-resolution structures and that too in a short timeframe depending upon device complexity. This could inspire progressive research in microfluidics, particularly finding applications in biomedical engineering and point-of-care diagnostics. This article gives an overview of how 3D printing aids in the manufacture of microfluidic devices for biological applications, as well as the existing 3D printing methods which are utilised for fabrication and the future perspective in the development of microfluidic devices.

Evolution of 3d printing technology  in fabrication of microfluidic devices  and biological applications:  a comprehensive review

The paper demonstrates an adaptation of a 3D printer (Prusa Mini+) with novel modules to develop a droplet generation system that generates combinatorial droplets from a standard 96 well plate....

Automated Dynamic Inlet Microfluidics System: 3D Printer Adaptation for Cost-Effective, Low Volume, On-Demand Multi-Analyte Droplet Generator

Soft contact lenses (SCLs) have recently been introduced as an alternative method for human tear protein sampling. However, SCLs are available in a variety of chemical compositions which affect protein binding specificity. Here we analyzed 8 different SCL materials to identify an optimal lens for tear protein sampling. Polymer contamination, mass spectrometry (MS) sample preparation method, total protein capture, individual protein specificity, and SCL cost were all assessed. Using a filter-aided sample prep (FASP) method with 4M guanidine for protein removal, only etafilcon A and verofilcon A did not have significant polymer contamination. Polymer was successfully removed using phosphate buffered saline (PBS) with S-Trap columns for all SCL materials, though yielding a slightly lower number of protein identifications per sample. Minor quantitative differences were observed between SCL materials. However, we also saw significant intersubject variation in protein abundance. Of all the assessed SCL materials, verofilcon A lenses yielded the most total protein while comfilcon A and senofilcon A had the least protein variability. As a newly released daily disposable modality (Precision 1, Alcon), verofilcon A has one of the longest predictable production schedules and one of the lowest costs per lens, making it beneficial for large-scale experiments and diagnostics. Furthermore, we demonstrate how protein binding bias with SCL tear sampling is useful for intra-experiment normalization. Overall, these experiments have led us to optimize our previous protocol for SCL tear protein sampling, highlighting important differences between SCL materials and identifying etafilcon A and verofilcon A as optimal materials for tear protein sampling.

/pdf/proteomic-specificity-of-soft-contact-lenses-for-tear-3gyoa54a.pdf

Proteomic Specificity of Soft Contact Lenses for Tear Protein Sampling

Abstract Direct 3D printing of active microfluidic elements on PCB substrates enables high-speed fabrication of stand-alone microdevices for a variety of health and energy applications. Microvalves are key components of microfluidic devices and liquid metal (LM) microvalves exhibit promising flow control in microsystems integrated with PCBs. In this paper, we demonstrate LM microvalves directly 3D printed on PCB using advanced digital light processing (DLP). Electrodes on PCB are coated by carbon ink to prevent alloying between gallium-based LM plug and copper electrodes. We used DLP 3D printers with in-house developed acrylic-based resins, Isobornyl Acrylate, and Diurethane Dimethacrylate (DUDMA) and functionalized PCB surface with acrylic-based resin for strong bonding. Valving seats are printed in a 3D caterpillar geometry with chamber diameter of 700 µm. We successfully printed channels and nozzles down to 90 µm. Aiming for microvalves for low-power applications, we applied square-wave voltage of 2 V pp at a range of frequencies between 5 to 35 Hz. The results show precise control of the bistable valving mechanism based on electrochemical actuation of LMs. 

3D printed microfluidic valve on PCB for flow control applications using liquid metal

We demonstrate a method to effectively 3D print microfluidic devices with high-resolution features using a biocompatible resin based on avobenzone as the UV absorber. Our method relies on spectrally shaping the 3D printer source spectrum so that it is fully overlapped by avobenzone’s absorption spectrum. Complete overlap is essential to effectively limit the optical penetration depth, which is required to achieve high out-of-plane resolution. We demonstrate the high resolution in practice by 3D printing 15 μm square pillars in a microfluidic chamber, where the pillars are separated by 7.7 μm and are printed with 5 μm layers. Furthermore, we show reliable membrane valves and pumps using the biocompatible resin. Valves are tested to 1,000,000 actuations with no observable degradation in performance. Finally, we create a concentration gradient generation (CG) component and utilize it in two device designs for cell chemotaxis studies. The first design relies on an external dual syringe pump to generate source and sink flows to supply the CG channel, while the second is a complete integrated device incorporating on-chip pumps, valves, and reservoirs. Both device types are seeded with adherent cells that are subjected to a chemoattractant CG, and both show clear evidence of chemotactic cellular migration. Moreover, the integrated device demonstrates cellular migration comparable to the external syringe pump device. This demonstration illustrates the effectiveness of our integrated chemotactic assay approach and high-resolution biocompatible resin 3D printing fabrication process. In addition, our 3D printing process has been tuned for rapid fabrication, as printing times for the two device designs are, respectively, 8 and 15 min.

Biocompatible High-Resolution 3D-Printed Microfluidic Devices: Integrated Cell Chemotaxis Demonstration

Human tear protein biomarkers are useful for detecting both ocular and systemic diseases. Unfortunately, existing tear film sampling methods (Schirmer strips (SS) and microcapillary tubes (MCT)) have significant drawbacks. Here we present an alternative tear protein sampling method using soft contact lenses (SCLs). First, we optimized SCL protein sampling in vitro, then performed in vivo studies in 6 human subjects. Using Etafilcon A SCLs and 4M guanidine-HCl for protein removal, we sampled an average of 60 +/- 31 ug of protein per eye. We also performed objective and subjective assessments of all sampling methods. Proteomic analysis by mass spectrometry (MS) revealed unique subsets of proteins for SS and SS/MCT methods. Additionally, SCLs had reduced levels of reflex tear protein zymogen granule protein 16 homolog B (ZG16B) versus SS and MCT. These experiments demonstrate SCLs as an accessible tear sampling method which may minimize reflex tearing and potentially aid biomarker discovery.

/pdf/human-tear-film-protein-sampling-using-soft-contact-lenses-21xvhnsp.pdf

Human Tear Film Protein Sampling Using Soft Contact Lenses

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Papers

Biocompatible High-Resolution 3D-Printed Microfluidic Devices: Integrated Cell Chemotaxis Demonstration

Human Tear Film Protein Sampling Using Soft Contact Lenses

Proteomic Specificity of Soft Contact Lenses for Tear Protein Sampling