3D-printed Platform Research Articles

Lensfree on-chip microscopy based on single-plane phase retrieval.

We propose a novel single-plane phase retrieval method to realize high-quality sample reconstruction for lensfree on-chip microscopy. In our method, complex wavefield reconstruction is modeled as a quadratic minimization problem, where total variation and joint denoising regularization are designed to keep a balance of artifact removal and resolution enhancement. In experiment, we built a 3D-printed field-portable platform to validate the imaging performance of our method, where resolution chart, dynamic target, transparent cell, polystyrene beads, and stained tissue sections are employed for the imaging test. Compared to state-of-the-art methods, our method eliminates image degradation and obtains a higher imaging resolution. Different from multi-wavelength or multi-height phase retrieval methods, our method only utilizes a single-frame intensity data record to accomplish high-fidelity reconstruction of different samples, which contributes a simple, robust, and data-efficient solution to design a resource-limited lensfree on-chip microscope. We believe that it will become a useful tool for telemedicine and point-of-care application.

Stay or Go? Neuronal Activity in Medial Frontal Cortex During a Voluntary Tactile Preference Task in Head-fixed Mice

The decision to move is influenced by sensory, attentional, and motivational cues. One such cue is the quality of the tactile input, with noxious or unpleasant sensations causing an animal to move away from the cue. Processing of painful and unpleasant sensation in the cortex involves multiple brain regions, although the specific role of the brain areas involved in voluntary, rather than reflexive movement away from unpleasant stimuli is not well understood. Here, we focused on the medial subdivision of secondary motor cortex, which is proposed to link sensory and contextual cues to motor action, and tested its role in controlling voluntary movement in the context of an aversive tactile cue. We designed a novel, 3D-printed tactile platform consisting of innocuous (grid) and mildly noxious (spiked) surfaces (50:50 % of total area), which enabled monitoring neuronal activity in the medial frontal cortex by two-photon imaging during a sensory preference task in head-fixed mice. We found that freely moving mice spent significantly less time on a spiked-surface, and that this preference was eliminated by administration of a local anesthetic. At the neuronal level, individual neurons were differentially modulated specific to the tactile surface encountered. At the population level, the neuronal activity was analyzed in relation to the events where mice chose to "stop-on" or "go-from" a specific tactile surface and when they "switched" surfaces without stopping. Notably, each of these three scenarios showed population activity that differed significantly between the grid and spiked tactile surfaces. Collectively, these data provide evidence that tactile quality is encoded within medial frontal cortex. The task pioneered in this study provides a valuable tool to better evaluate mouse models of nociception and pain, using a voluntary task that allows simultaneous recording of preference and choice. Grant support from NS109287 (G.A.), NS096246 (Y.U.), DK116624 (Y.U.) and NS113189 (Y.U.), the Iowa Neuroscience Institute, and the Williams- Cannon faculty fellowship (G.A). A.K. was supported by a predoctoral fellowship through NIH T32 Grant GM067795.

Multi‐Material, Multi‐Process, Planar, and Nonplanar Additive Manufacturing of Piezoelectric Devices

Nonplanar multi‐material additive manufacturing (AM) of piezoelectric devices is an important step for innovation in digital manufacturing. Herein this work, the development of a manufacturing platform based on multi‐material multi‐process AM that enables fabrication of piezoelectric and conductive electrode materials with complex planar and nonplanar (conformal) structures is reported. Also, the development of conductive and piezoelectric paste‐like printing materials, herein called inks, for extrusion‐based direct‐writing AM processes is presented. The developed inks are highly stretchable (e.g., up to 100% before breaking), easy to process, and less toxic compared to existing solvent evaporation‐based inks in the literature. Several piezoelectric energy‐harvesting (PEH) devices are fabricated. The innovative inks within a multi‐material multi‐process 3D printing platform can substantially broaden the design space of multi‐material AM and open up new opportunities for the production of application‐oriented parts that are more integrable, conformable, scalable, and versatile.

Single-atom Ce-N-C nanozyme bioactive paper with a 3D-printed platform for rapid detection of organophosphorus and carbamate pesticide residues

Rapid detection of pesticide residues based on enzyme mimics has recently attracted much interest. However, most nanozymes have low activity. Herein, a “single-atom Ce-N-C nanozyme” (SACe-N-C nanozyme) was rationally devised and verified to mimic peroxidase (POD-like) with superior activity. Based on its high POD-like activities and cascaded catalytic reactions with acetylcholinesterase (AChE), we constructed a bioactive paper for the detection of pesticide residues, which offered a portable approach to monitor fruits and vegetables within 30 min. More importantly, a 3D printed platform was integrated on the basis of SACe-N-C bioactive paper to achieve on-site portable testing of omethoate, methamidophos, carbofuran, and carbosulfan, showing limits of detection (LODs) of 55.83, 71.51, 81.81, and 74.98 ng/mL, respectively. The recovery rates were 84.09–104.68%. This study provided new insight into the design of novel single-atom nanozymes for cascaded catalytic detection and other rapid detection applications with high efficiency and low cost.

3D nanoprinting via spatially controlled assembly and polymerization

Macroscale additive manufacturing has seen significant advances recently, but these advances are not yet realized for the bottom-up formation of nanoscale polymeric features. We describe a platform technology for creating crosslinked polymer features using rapid surface-initiated crosslinking and versatile macrocrosslinkers, delivered by a microfluidic-coupled atomic force microscope known as FluidFM. A crosslinkable polymer containing norbornene moieties is delivered to a catalyzed substrate where polymerization occurs, resulting in extremely rapid chemical curing of the delivered material. Due to the living crosslinking reaction, construction of lines and patterns with multiple layers is possible, showing quantitative material addition from each deposition in a method analogous to fused filament fabrication, but at the nanoscale. Print parameters influenced printed line dimensions, with the smallest lines being 450 nm across with a vertical layer resolution of 2 nm. This nanoscale 3D printing platform of reactive polymer materials has applications for device fabrication, optical systems and biotechnology.

Multi-material 3D-Printing Soft Robot Functional Component

—3D printing has a wide range of applications and addresses many challenges inherited from conventional manufacturing techniques. This paper presents a dual-extrusion 3D printing platform capable of printing soft materials for soft robot functional components. Dow Corning-737 and Dragon Skin-0030 materials are used. Single-line experiment is used to determine the optimization parameters of extrusion pressure, printing speed, and layer thickness of the developed multi-material 3D printing platform. A soft valve consisting of two soft materials has been fabricated, and the printed soft valve is verified by a performance experiment. The results indicate that the developed 3D printing platform can fabricate soft robot functional components at high speed with high accuracy.

Small-Scale Continuous Drug Product Manufacturing using Dropwise Additive Manufacturing and Three Phase Settling for Integration with Upstream Drug Substance Production

The pharmaceutical industry has traditionally relied on mass manufacturing to make its products. This has created multiple problems in the drug supply network, including long production times, inflexible and sluggish manufacturing and lack of personalized dosing. The industry is gradually adapting to these challenges and is developing novel technologies to address them. Continuous manufacturing and 3D printing are two promising techniques that can revolutionize pharmaceutical manufacturing. However, most research studies into these methods tend to treat them separately. This study seeks to develop a new processing route to continuously integrate a 3D printing platform (Drop-on-Demand, DoD, printing) with crystallization that is generally the final step of the active ingredient manufacturing. Accomplishing this integration would enable harnessing the benefits of each method- personalized dosing of 3D printing and flexibility and speed of continuous manufacturing.A novel unit operation, three-phase settling (TPS), is developed to integrate DoD with the upstream crystallizer. To ensure on-spec production of each printed dosage, two process analytical technology tools are incorporated in the printer to monitor drug loading in manufactured drug products in real time. Experimental demonstration of this system is carried out via two case studies: the first study uses an active ingredient celecoxib to test the standalone operation of TPS; the second study demonstrates the operation of the integrated system (crystallizer – TPS – DoD) to continuously make drug products for the active ingredient- lomustine. A dissolution test is also performed on the manufactured and commercial lomustine drug products to compare their dissolution behavior.

Recent Utilization of 3D-Bioprinting Methods for Breast Cancer Models

<p style="text-align: justify;">Animal models are the most commonly used model that helps to improve the understanding of the genetic alterations that occur in humans during the carcinogenic environment. Furthermore, these models play a pivotal role in the illustration of tumorigenesis and therapeutic strategies. With the advancement in molecular biology, the use of nanomedicine for breast cancer treatment has progressed, and more is expected to be done in the future pretrial and clinical models to achieve more success. The biocompatibility of 3D printing platforms has been reported to be adequate in terms of cell viability; however the effects on gene expression and functional aspects have received less attention. Various mechanical and visual disruptions to cells are involved depending on the type of bioprinter employed. Additional research into the mechanical and optical effects of the bioprinting process will provide more insight into the 3D printing technique&rsquo; biocompatibility. To investigate the microenvironment of breast tumours and 3D bioprinting methods have also been studied. Modalities for bioprinting include extrusion-based (EBB) printing, droplet-based (DBB) printing and laser-based bioprinting. Different research has indicated that new developments of novel cancer modelling have emerged with 3D bioprinting technology. Those studies need to be properly explained and analyses in a Broadway in this review and to help in the progress of cancer research. <p style="text-align: justify;"><strong>Key words: </strong>3D printing, Extrusion-Based Bioprinting, Photocuring-Based Bioprinting, Droplet-based Bioprinting, Microenvironment.

Extrusion and thermal control design of an on-orbit 3D printing platform

On-orbit manufacturing can reduce the cost and time needed by space exploration missions because in-situ maintenance activities can be achieved without the need for additional launches. Furthermore, recent developments in materials science in terms of better mechanical and thermal performance have allowed this application to become a potential reality. However, the deployment of on-orbit manufacturing presents several challenges, including the lack of convective heat transfer and human intervention. This paper proposes an on-orbit 3D printing device capable of operating at a temperature up to 400 °C in the vacuum environment. To validate its feasibility for on-orbit manufacturing, we designed four extruders with different characteristics. We investigated the temperature profiles across the extruders under the vacuum condition through a heat transfer model. Based on the thermal analysis, a thermal control method, which combines the Proportion (P) and Fuzzy Proportion and Integration (Fuzzy PI) strategies, is designed to regulate the 3D printing device operation. With the extrusion rate of 8654.6 mm3 /h and the printing temperature at 400 °C, the melting and solidification status of the PEEK (Polyether ether ketone) material is verified.

Alginate Self-Crosslinking Ink for 3D Extrusion-Based Cryoprinting and Application for Epirubicin-HCl Delivery on MCF-7 Cells.

3D-printed hydrogels are particularly advantageous as drug-delivery platforms but their loading with water-soluble active compounds remains a challenge requiring the development of innovative inks. Here, we propose a new 3D extrusion-based approach that, by exploiting the internal gelation of the alginate, avoids the post-printing crosslinking process and allows the loading of epirubicin-HCl (EPI). The critical combinations of alginate, calcium carbonate and d-glucono-δ-lactone (GDL) combined with the scaffold production parameters (extrusion time, temperature, and curing time) were evaluated and discussed. The internal gelation in tandem with 3D extrusion allowed the preparation of alginate hydrogels with a complex shape and good handling properties. The dispersion of epirubicin-HCl in the hydrogel matrix confirmed the potential of this self-crosslinking alginate-based ink for the preparation of 3D-printed drug-delivery platforms. Drug release from 3D-printed hydrogels was monitored, and the cytotoxic activity was tested against MCF-7 cells. Finally, the change in the expression pattern of anti-apoptotic, pro-apoptotic, and autophagy protein markers was monitored by liquid-chromatography tandem-mass-spectrometry after exposure of MCF-7 to the EPI-loaded hydrogels.

Biomimetic 3D printed PCL/TCP/GelMA scaffolds with improved osteogenesis and angiogenesis for non-load bearing applications

The strategy of biomimicry is crucial to effectively improve osteogenesis and angiogenesis for bone tissue engineering scaffolds, however, this approach remains challenging. In this study, we used a composite including PCL, TCP, and GelMA to mimic the heterogeneous bone composition. Meanwhile, hierarchical pores were successfully created through 3D printing, surface modification, and GelMA infiltration. Results showed that our 3D printing platform presented a high level of microstructural control of scaffolds and produced scaffolds with a porosity of 68.48±0.82%, an open porosity percentage of 97.81±1.44%, and a compressive strength of 2.68±0.03 MPa. In addition, triangular pores of 495.03±3.67 μm, ECM-like pores of 126±31 μm, and surface modified micro/nano roughness were observed from our 3D printed composite scaffolds leading to significantly improved hydrophilicity. Finally, in vivo results demonstrated that our 3D printed composite scaffolds exhibited enhanced osteogenesis and expedited transition from vascular formation and ECM deposition to mineralized bone formation, which was promising for clinical translations towards non-load bearing bone fixations.

Integrated Platform Addressing the Finger-Prick Blood Processing Challenges of Point-of-Care Electrical Biomarker Testing.

Continued advances in label-free electrical biosensors pave the way to simple, rapid, cost-effective, high-sensitivity, and quantitative biomarker testing at the point-of-care setting that would profoundly transform healthcare. However, implementation in routine diagnostics is faced with significant challenges associated with the inherent requirement for biofluid sample processing before and during testing. We present here a simple yet robust autonomous finger-prick blood sample processing platform integrated with nanoscale field-effect transistor biosensors and demonstrate the feasibility of measuring the SARS-CoV-2 nucleocapsid protein. The 3D-printed platform incorporates a high-yield blood-to-plasma separation module and a delay valve designed to terminate the assay at a specific time. The platform is driven by hydrostatic pressure to efficiently and automatically dispense plasma and washing/measurement buffer to the nanosensors. Our model study demonstrates the feasibility of detecting down to 1.4 pg/mL of the SARS-CoV-2 nucleocapsid protein within 25 min and with only minimal operator intervention.

Integrated multi-material portable 3D-printed platform for electrochemical detection of dopamine and glucose.

3D-printing has become a fundamental part of research in many areas of investigation since it provides rapid and personalized production of parts that meet very specific user needs. Biosensing is not an exception, and production of electrochemical sensors that can detect a variety of redox mediators and biologically relevant molecules has been widely reported. However, most 3D-printed electrochemical sensors detailed in the literature rely on big, individual, single-material electrodes that require large sample volumes to perform effectively. Our work exploits multi-material fused filament fabrication 3D-printing to produce a compact electrochemical sensor able to operate with only 100 μL of sample. We report cyclic voltammetry, differential pulse voltammetry, and chronoamperometry results to assess sensor performance and sensitivity. We investigated the influence of layer print orientation and layer thickness on the electrochemical performance of the sensor, and used the optimal parameters to produce the final device. The integrated 3D-printed platform successfully detects electrochemical activity for hexaammineruthenium(III) chloride and potassium ferricyanide (0.1 mM to 2 mM in 100 mM KCl), dopamine (50 μM to 1 mM in 1×PBS), and glucose via mediated amperometric glucose oxidase enzyme-based sensing (1 mM to 12 mM in 1×PBS), indicating good acceptance of biological modification. These results reveal the exciting potential of multi-material 3D-printing and how it can be used for the rapid development of efficient, small, integrated, personalized electrochemical biosensors.

A 3D-printed transfusion platform reveals beneficial effects of normoglycemic erythrocyte storage solutions and a novel rejuvenating solution.

A set of 3D-printed analytical devices were developed to investigate erythrocytes (ERYs) processed in conventional and modified storage solutions used in transfusion medicine. During storage, prior to transfusion into a patient recipient, ERYs undergo many chemical and physical changes that are not completely understood. However, these changes are thought to contribute to an increase in post-transfusion complications, and even an increase in mortality rates. Here, a reusable fluidic device (fabricated with additive manufacturing technologies) enabled the evaluation of ERYs prior to, and after, introduction into a stream of flowing fresh ERYs, thus representing components of an in vivo ERY transfusion on an in vitro platform. Specifically, ERYs stored in conventional and glucose-modified solutions were assayed by chemiluminescence for their ability to release flow-induced ATP. The ERY's deformability was also determined throughout the storage duration using a novel membrane transport approach housed in a 3D-printed scaffold. Results show that hyperglycemic conditions permanently alter ERY deformability, which may explain the reduced ATP release, as this phenomenon is related to cell deformability. Importantly, the reduced deformability and ATP release were reversible in an in vitro model of transfusion; specifically, when stored cells were introduced into a flowing stream of healthy cells, the ERY-derived release of ATP and cell deformability both returned to states similar to that of non-stored cells. However, after 1-2 weeks of storage, the deleterious effects of the storage were permanent. These results suggest that currently approved hyperglycemic storage solutions are having adverse effects on stored ERYs used in transfusion medicine and that normoglycemic storage may reduce the storage lesion, especially for cells stored for longer than 14 days.

A Battery Powered on-Chip Peristaltic Pump for Lab-On-A-Chip Applications

Low-cost and controllable fluid manipulation in small scale is important to biomedical research, and disease testing and diagnostics. In the midst of global disease outbreaks and pandemics such as Ebola and Covid-19, rapid and low-cost testing and diagnostics have become even more crucial. Lab-on-a-chip platforms are good candidates to be applied in these circumstances due their small footprints and lower-costs which enable rapid-prototyping of these devices. However, providing controlled fluid flow handling in small scale for on-chip devices is not currently suitable for point-of-care applications due to the expensive fluid pumping systems that currently used in most of the lab-on-a-chip devices. In this work, a low-cost and practical peristaltic pump is developed using 3D printing and open-sourced microcontroller platform Arduino boards. The entire system is designed to be portable and capable of producing metered fluid flow in small scale devices. The developed device is characterized to provide adjustable fluid flow control between 1.7 µL/s to 23 µL/s which is suitable for many on-chip applications. The peristaltic pump developed in this work can be used in lab-on-a-chip applications due to its simplicity and low-cost.

3D-Printed Miniature Robots with Piezoelectric Actuation for Locomotion and Steering Maneuverability Applications

The miniaturization of robots with locomotion abilities is a challenge of significant technological impact in many applications where large-scale robots have physical or cost restrictions. Access to hostile environments, improving microfabrication processes, or advanced instrumentation are examples of their potential use. Here, we propose a miniature 20 mm long sub-gram robot with piezoelectric actuation whose direction of motion can be controlled. A differential drive approach was implemented in an H-shaped 3D-printed motor platform featuring two plate resonators linked at their center, with built-in legs. The locomotion was driven by the generation of standing waves on each plate by means of piezoelectric patches excited with burst signals. The control of the motion trajectory of the robot, either translation or rotation, was attained by adjusting the parameters of the actuation signals such as the applied voltage, the number of applied cycles, or the driving frequency. The robot demonstrated locomotion in bidirectional straight paths as long as 65 mm at 2 mm/s speed with a voltage amplitude of only 10 V, and forward and backward precise steps as low as 1 µm. The spinning of the robot could be controlled with turns as low as 0.013 deg. and angular speeds as high as 3 deg./s under the same conditions. The proposed device was able to describe complex trajectories of more than 160 mm, while carrying 70 times its own weight.

Single-molecule and particle detection on true portable microscopy platforms

Point-of-care technologies (POCT) that enable early disease detection and therapeutic monitoring are crucial for the next generation of diagnostics and personalized medicine. Meanwhile, there is a global need for low-cost POCT that makes advanced diagnostic tools accessible to resource-limited settings. Recently, several mobile imaging platforms for single-molecule and particle detection have been developed, which greatly improve the detection sensitivity of molecular assays. This review highlights emerging technologies that achieve single-molecule and particle optical detection on true portable platforms. Miniature, high-sensitivity imaging devices based on smartphones, single-board computers (i.e., Raspberry Pi systems), lab-on-a-chip systems, and 3D-printed microscopy platforms are discussed.

Multifunctional 3D-printed platform integrated with a smartphone ambient light sensor for halocarbon contaminants monitoring

3D-printed platforms integrated with smartphone light sensors have become a powerful tool for the development of frugal and facile biosensing systems. Herein, we report a 3D-printed platform for multimodal analysis (3D-PMA) based on a smartphone ambient light sensor (ALS). The proposed approach was first validated using a microtiter plate reader, and then its application potential was demonstrated by measuring halohydrin dehalogenase activities employing three different sample modes, viz . using enzyme-linked immunosorbent assay (ELISA) plate strips, cuvettes, and the glass fiber membrane as sample containers. For real-sample analysis, 1,3-dichloro-2-propanol (1,3-DCP), a toxic halogenated compound, was successfully detected in spiked river water samples with recoveries in the range of 101.95–109.70%. After demonstrating the suitability for liquid-phase assays, the 3D-PMA was also optimized for 1,3-DCP detection using a glass fiber membrane. The detection could be done using a 10 μ L reaction system with an assay time of 2 min. The assay showed two linear ranges. The calibration equation of Y = 81.687x + 140.060 was obtained from the lower part of the calibration curve and was used to calculate the detection limit of the system. Under optimized conditions, a detection limit of 80 μ M was achieved for 1,3-DCP. The small size of the device endows it with great promise for use as a benchtop and an on-demand detection system. The proposed low-cost and portable system has great potential for the (bio) sensing of different biological and environmental samples where biocomponent-analyte interaction leads to a color change of the reaction system, indicating its applicability in resource-constrained settings. • A smartphone assisted portable system was developed for environmental contaminants monitoring. • 3D-printed platform demonstrated potential utility for multimodal analysis. • Smartphone Ambient Light Sensor as a potential transducer for halocarbon detection.

Design of Automatic Controller System for Three Axis 3D Printing Platform

With the development of society and the continuous improvement of the level of automation, automatic three-dimensional work platform is more and more popular, but now the three-dimensional work platform has a single function, and the waste of capacity is a serious problem. Therefore, this paper uses STM32F429 MCU to design a set of replaceable working position of the three axis control platform. The design of the table with replaceable work head, by identifying the ID on the head, change the control mode, enhance the functional diversity of the three-axis platform. In addition, in order to improve the universality of the system, the platform has many external communication interfaces, visual man-machine interface and LAN network communication functions.

Scalable visible light 3D printing and bioprinting using an organic light-emitting diode microdisplay

SummaryTo address current unmet needs in terms of scalability and material biocompatibility for future photocrosslinking-based additive manufacturing technologies, emergent platform designs are in inexorable demand. In particular, a shift from the present use of cell-damaging UV light sources in light-based three-dimensional (3D) bioprinting methods demands new platforms. We adopted an organic light-emitting diode (OLED) microdisplay as a digital visible light modulator to create a 3D printing platform modality that offers scalability and multi-material capability while forgoing the need for UV photocrosslinking. We formulate biocompatible inks that are visible light-crosslinkable with relatively quick photoinitiation rates. We demonstrated successful attachment and rapid growth of primary human dermal fibroblast-adult (HDF-a) cells on biological substrates fabricated using the OLED platform. This platform incites new possibilities by providing a simple-yet-effective means for low-cost, high-throughput, and multi-material 3D fabrication of functional structures made of polymers, ceramic composites, and biomaterials.