Thermal Inkjet Research Articles

Novel Combinatorial Strategy Using Thermal Inkjet Bioprinting, Chemotherapy, and Radiation on Human Breast Cancer Cells; an In-Vitro Cell Viability Assessment

Background: Breast cancer (BC) continues to have the second highest mortality amongst women in the United States after lung cancer. For 2021, the American Cancer Association predicted 281,550 new invasive breast cancer cases besides 49,290 new cases of non-invasive breast cancer and 43,600 deaths from the metastatic disease. A treatment modality is radiation therapy, which is given for local control as well as palliation of patient symptoms. The initial step of new drug development is in-vitro cell studies, which help describe new drug properties and toxicities. However, these models are not optimal, and better ones have yet to be determined. This study uses bioprinting technology to elucidate the sensitivity of tumor cells to the combination of palbociclib (PD) and letrozole (Let) treatment. We hypothesize that this technology could serve as a model to predict treatment outcomes more efficiently. Methods: The breast cancer cell lines MCF7 and MDA-MB-231 as well as the normal breast epithelial cell line, MCF-10A, were treated with PD-Let with and without radiotherapy (RT), and cell viability was compared in pairwise fashion for thermally inkjet bioprinted (TIB) and manually seeded (MS) cells. Results: In absence of radiation, the TIB MCF7 cells have 2.5 times higher viability than manually seeded (MS) cells when treated with 100 µM palbociclib and 10 µM letrozole, a 36% higher viability when treated with 50 µM palbociclib and 10 µM letrozole, and an 8% higher viability when treated with 10 µM palbociclib and 10 µM letrozole. With 10 Gy of radiation, TIB cells had a 45% higher survival rate than MS cells at the lowest palbociclib concentration and a 29% higher survival rate at the intermediate palbociclib concentration. Without radiation treatment, at a concentration of 10 μM PD-Let, TIB MDA-MB-231 cells show a 8% higher viability than MS cells when treated with 10 µM PD and 10 µM Let; at higher drug concentrations, the differences disappeared, but some 1.7% of the TIB MDA-MB-231 cells survived exposure to 150 μM of PD + 10 μM letrozole vs. none of the MS cells. These cells are more radiation sensitive than the other cell lines tested and less sensitive to the combo drug treatments. We observed an 18% higher survival of TIB MCF-10A cells without radiation treatment when exposed to 10 μM PD + 10 μM Let but no difference in cell survival between the two groups when radiation was applied. Independent of growth conditions, TIB cells did not show more resistance to radiation treatment than MS cells, but a higher resistance to the combo treatment was observed, which was most pronounced in the MCF-7 cell line. Conclusion: Based on these results, we suggest that TIB used in in-vitro models could be a feasible strategy to develop and/or test new anticancer drugs.

Controlling Droplet Impact Velocity and Droplet Volume: Key Factors to Achieving High Cell Viability in Sub-Nanoliter Droplet-based Bioprinting

Three-dimensional (3D) bioprinting systems serve as advanced manufacturing platform for the precise deposition of cells and biomaterials at pre-defined positions. Among the various bioprinting techniques, the drop-on-demand jetting approach facilitates deposition of pico/nanoliter droplets of cells and materials for study of cell-cell and cell-matrix interactions. Despite advances in the bioprinting systems, there is a poor understanding of how the viability of primary human cells within sub-nanoliter droplets is affected during the printing process. In this work, a thermal inkjet system is utilized to dispense sub-nanoliter cell-laden droplets, and two key factors – droplet impact velocity and droplet volume – are identified to have significant effect on the viability and proliferation of printed cells. An increase in the cell concentration results in slower impact velocity, which leads to higher viability of the printed cells and improves the printing outcome by mitigating droplet splashing. Furthermore, a minimum droplet volume of 20 nL per spot helps to mitigate evaporation-induced cell damage and maintain high viability of the printed cells within a printing duration of 2 min. Hence, controlling the droplet impact velocity and droplet volume in sub-nanoliter bioprinting is critical for viability and proliferation of printed human primary cells.

Research on Thermal Inkjet Technology Based on CFD

In this paper, a thermal inkjet printing simulation model is established in the CFD simulation platform, and the influence of inkjet driver parameters and ink physical parameters on the printing process is studied by numerical simulation. The evaporation-condensation model is coupled with the VOF multiphase flow model in Fluent software to establish a thermal inkjet printing process simulation model. Based on the orthogonal test method, we investigate the influence of fluid physical parameters (ink viscosity, surface tension) and inkjet driver parameters (heater temperature value) on droplet formation by changing the physical parameters of the material and the boundary conditions of the model. Through the comparison of the results, exploring the adjustment rules of thermal inkjet technology and obtaining the optimal combination of material and process parameters for high-quality ink drop formation.

An overview on 3D Printed Medicine

Three-dimensional printing (3DP) is a digitally-controlled additive manufacturing technique used for fast prototyping. This paper reviews various 3D printing techniques like Selective Laser Sintering (SLS), Fused Deposition Modeling, (FDM), Semi-solid extrusion (SSE), Stereolithography (SLA), Thermal Inkjet (TIJ) Printing, and Binder jetting 3D Printing along with their application in the field of medicine. Normal medicines are based on the principle of “one-size-fits-all”. This is not true always, it is possible medicine used for curing one patient is giving some side effects to another. To overcome this drawback “3D Printed medicines” are developed. In this paper, 3D printed medicines forming different Active Pharmaceutical Ingredients (API) are reviewed. Printed medicines are capable of only curing the diseases, not for the diagnosis. Nanomedicines have “theranostic” ability which combines therapeutic and diagnostic. Nanoparticles are used as the drug delivery system (DDS) to damaged cells’ specific locations. By the use of nanomedicine, the fast recovery of the disease is possible. The plant-based nanoparticles are used with herbal medicines which give low-cost and less toxic medication called nanobiomedicine. 4D and 5D printing technology for the medical field are also enlightened in this paper.

Inkjet Printed Melatonin on Poly(vinyl alcohol) Oral Films: Uptake in an Ex Vivo Oral Mucosal Pellicle Model

There is a growing interest in the use of melatonin in preventing radiation-induced mucositis with potential beneficial effects including prevention of mucosal damage, the emergence of ulcers and the loss of proliferative progenitor stem cells caused by radiation. Local drug delivery to the oral cavity is influenced by the oral mucosal pellicle which serves as a protective barrier between the oral epithelial surface and the external environment. In this study, we explore two key areas. Firstly, the use of thermal inkjet printing to improve the precision of drug deposition on polymeric oral films. Secondly, investigate melatonin release and penetration across an ex vivo oral mucosal pellicle model into the epithelial cancer cell line (TR146 cells). Our findings show that the deposited melatonin crystallized on the surface of the Polyvinyl Alcohol (PVA) film as the jetted droplets dried, consistent with previous work on in-jetted pharmaceutical solutions. The solid state of the deposited melatonin was further confirmed in attenuated total reflection Fourier transform infrared studies as crystalline. In addition, no new bonds detected which indicates the absence of new chemical bonds and interactions between melatonin and PVA. Investigating melatonin release and penetration across ex vivo oral mucosal pellicle model into the epithelial cancer cell line (TR146 cells) found that the amount of melatonin released was lower in the presence of saliva, likely due to the saliva initiating the formation of the mucosal pellicle through mucin–mucin interactions.

Fabrication of a time-temperature indicator by inkjet printing of a spore-based bio-ink

Bio-indicators are nowadays being increasingly used by the food and drug industry to detect the changes in environmental conditions. In this study, a time-temperature indicator (TTI) is fabricated by using an office thermal inkjet printer to print a new custom-made bio-ink for detecting changes in color that occur with time and temperature variation. In lieu of the regular inks, the TTI uses solutions containing Geobacillus stearothermophilus (G. stearothermophilus) and Bacillus atrophaeus (B. atrophaeus) spores, tryptic soy broth, pH indicators, and a combination of polyvinyl alcohol and borax as the gelling agent, to be dispensed from the printer cartridge. Following the printing process, the samples thus obtained are coated with a protective film to avoid moisture loss. The effects of bio-ink gelatinization, pH, color intensity, and print resolution on bacterial printing are determined by varying the level of each parameter. The presence of the protective film on printed bacteria is found not only to lead to the growth and proliferation of bacteria but also to reveal color with sharper contrast. The indicator’s initial and final colors are modified by varying the pH levels of the solutions. Increasing color intensity (20%, 40%, 60%, 80%, and 100%) in the software settings is used to induce significant enhancements in the printed bacterial populations, thereby controlling the rate of color change. It is, moreover, observed that changes in print resolution do not have any significant effects on the populations of printed bacterial spores. In general, the TTI’s endpoint may be modified so as to suit various pharmaceutical and food applications.

Fabrication of Magnetic Polymer Nanocomposites Using Inkjet 3D Print Technology

Tailored magnetic nanocomposites have applications ranging from communications technologies to medical devices. Using a novel 3D fabrication technique that combines thermal inkjet and powder bed fusion print technologies, magnetic composites were fabricated by jetting magnetic nanoparticle containing ink into a polymer powder bed and then heat fusing the ink/polymer matrix. The goals were to demonstrate the feasibility of nanocomposite fabrication with controllable magnetic properties by varying the volume fraction of magnetic ink jetted into the polymer as well as to experimentally validate the effective medium theory based model developed to predict the permeability of the composites as a function of its magnetic particle concentration. As expected, magnetic susceptibility and saturation magnetization were seen to increase with the volume fraction of magnetic particles in the composites.

Patterns of Knowledge Flow: Cycles of Divergence and Convergence in Printers

This paper considers technological trajectories as a series of problem-solving activities, manifesting the pattern of divergence-convergence knowledge flow. We propose that technological trajectories diverge when new knowledge is able to solve the problem of most concern. Relatedly, technological trajectories converge when existing knowledge becomes obsolescent in the face of new problems. To illustrate our ideas, we choose to study the technological evolution of the thermal inkjet print head, using key-route search and the patent assignee cross-citation network. The thermal inkjet print head experienced three cycles of divergence-convergence knowledge flow, each of which is characterized by the problem of most concern and referred solution. To enhance the rigor of our analysis, we also draw on archival data to examine in more detail the identified main paths as well as the assignee cross-citation network.

The operating regularity of the stepper motor of thermal inkjet printers and its application in the China national accreditation service 2017ZO146 altered documents identification proficiency test

With the continuous innovation of inkjet printing technology, the methods of using inkjet printers for falsification have also constantly evolved, leading to increasing difficulties in identifying printing alterations made by the same inkjet printer. This paper mainly studies the operating regularity of the stepper motor of inkjet printers to determine the operating mechanism of inkjet printers and thus to identify whether documents had been tampered with. To detect the operating track of the stepper motor, 154 documents printed by 22 different brands and models of thermal inkjet printers were studied according to the periodic morphological characteristics of ink marks and the track of the stepper motor during different printing processes. As a result: ① the maximum gauge of 22 printheads was found to be different and ② the different distribution of ink marks were mainly affected by the direction and speed of the stepper motor. The track of the stepper motor was able to be determined by the periodic morphological characteristics of the ink marks combined with the maximum gauges, and could be used to judge how many times a document was printed. The observed regularities were evaluated by the CNAS 2017ZO146 test, a national proficiency test in China. In conclusion, using the summarized operating regularities of the stepper motor, it is possible to identify printing alterations made by the same thermal inkjet printer.

Thin-Film MEMS Resistors with Enhanced Lifetime for Thermal Inkjet.

In this paper, the failure mechanisms of the thermal inkjet thin-film resistors are recognized. Additionally, designs of resistors to overcome these mechanisms are suggested and tested by simulation and experiment. The resulting resistors are shown to have improved lifetimes, spanning an order of magnitude up to 2 × 109 pulses. The thermal failure mechanisms were defined according to the electric field magnitude in three critical points—the resistor center, the resistor–conductor edge, and the resistor thermal “hot spots”. Lowering the thermal gradients between these points will lead to the improved lifetime of the resistors. Using MATLAB PDE simulations, various resistors shapes, with different electric field ratios in the hot spots, were designed and manufactured on an 8″ silicon wafer. A series of lifetime experiments were conducted on the resistors, and a strong relation between the shape and the lifetime of the resistor was found. These results have immediate ramifications regarding the different printing apparatuses which function with thermal inkjet technology, allowing the commercial production of larger thermal printheads with high MTBF rate. Such heads may fit fast and large 3D printers.

3D Printing in Pharmaceutical Technology – A Review

Three-dimensional printing is a revolutionary technique that uses computer aided design software and programming to create three dimensional objects by placing material on a substrate. 3D printing is an additive layer manufacturing techniques, where consecutive layers of material are deposited or solidified to form a 3D structure. Medicinal substances is configured in three dimensional with computer assisted design module and transformed to a machine legible form which suggests the exterior emerge of the 3D dose form, then it sliced this surface into number of different printable coats and convey these layers to the machine. The different 3D printing techniques has been developing and developed to fabricate novel solid dosage forms, which are among the most well-known and discrete products today. The 3D printing process desires to be espoused by pharmaceutical sector and capable of exploring the marvels fetched by the approach. 3D printing can include a very new possibilities to optimized medicine. The current review is an effort of briefing various methods (Thermal Ink jet printing, Ink jet printing, Fused deposition modeling, Extrusion 3D Printing, Zip dose, Hot melt extrusion, 3D printer, Stereolithography, Selective laser sintering, Laser-Based Writing System, Continuous Layer Interface Production, Powder Based 3D Printing), advantages, limitations, applications of 3D printing in pharmaceutical technology.

Highly stretchable hydrogels for sensitive pressure sensor and programmable surface patterning by thermal bubble inkjet technology

AbstractHydrogels with tough strength, programmable deformation are crucial for their practical applications. In this work, we reported the preparation and the programmable shape deformations of highly stretchable hydrogel. The graphene oxide/polyacrylamide/sodium alginate composite hydrogel was prepared, its microstructure and mechanical properties were studied. An aqueous calcium solution was selectively printed onto the hydrogel surfaces using an inkjet printer, resulting in programmable deformation of the composite hydrogel by creating regions of swelling/deswelling when subjected to external stimulations. Next, we fabricated a pressure‐capacitance hydrogel sensor to demonstrate its application. Furthermore, the deformation rate and extent of the hydrogels can be controlled by adjusting the printing pattern position, number, length, and calcium solution concentration. Finally, several complex 2D and 3D shapes were fabricated by printing appropriate patterns on one or both surfaces of the hydrogel sheets.

Thermal Bioprinting Causes Ample Alterations of Expression of LUCAT1, IL6, CCL26, and NRN1L Genes and Massive Phosphorylation of Critical Oncogenic Drug Resistance Pathways in Breast Cancer Cells.

Bioprinting technology merges engineering and biological fields and together, they possess a great translational potential, which can tremendously impact the future of regenerative medicine and drug discovery. However, the molecular effects elicited by thermal inkjet bioprinting in breast cancer cells remains elusive. Previous studies have suggested that bioprinting can be used to model tissues for drug discovery and pharmacology. We report viability, apoptosis, phosphorylation, and RNA sequence analysis of bioprinted MCF7 breast cancer cells at separate timepoints post-bioprinting. An Annexin A5-FITC apoptosis stain was used in combination with flow cytometry at 2 and 24 h post-bioprinting. Antibody arrays using a Human phospho-MAPK array kit was performed 24 h post-bioprinting. RNA sequence analysis was conducted in samples collected at 2, 7, and 24 h post-bioprinting. The post-bioprinting cell viability averages were 77 and 76% at 24 h and 48 h, with 31 and 64% apoptotic cells at 2 and 24 h after bioprinting. A total of 21 kinases were phosphorylated in the bioprinted cells and 9 were phosphorylated in the manually seeded controls. The RNA seq analysis in the bioprinted cells identified a total of 12,235 genes, of which 9.7% were significantly differentially expressed. Using a ±2-fold change as the cutoff, 266 upregulated and 206 downregulated genes were observed in the bioprinted cells, with the following 5 genes uniquely expressed NRN1L, LUCAT1, IL6, CCL26, and LOC401585. This suggests that thermal inkjet bioprinting is stimulating large scale gene alterations that could potentially be utilized for drug discovery. Moreover, bioprinting activates key pathways implicated in drug resistance, cell motility, proliferation, survival, and differentiation.

Retraction: “Numerical study of a bubble driven micromixer based on thermal inkjet technology” [Phys. Fluids 31, 062006 (2019)

Retraction: “Numerical study of a bubble driven micromixer based on thermal inkjet technology” [Phys. Fluids 31, 062006 (2019)

3D printing of ceramics and graphene circuits-on-ceramics by thermal bubble inkjet technology and high temperature sintering

Alumina ceramics and graphene circuits-on-ceramics were 3D printed using inkjet technology. Water-based binders for ceramics and graphene oxide inks were prepared and jetted through thermal inkjet printhead. To increase the density of the 3D printed ceramics, two steps sintering and one step infiltration were performed. The sintering temperature dependent structure properties of the printed ceramics were systematically studied. The 3D printed α-Al2O3 ceramic sintered at 1600 °C for 2 h has achieved maximum density of 95.2%, volume shrinkage rate of 32%, Vickers hardness of 291.6 Hv, surface roughness of 3.7 μm, and maximum compression strength and flexural strength of 89 MPa and 49.4 MPa, respectively. The average adhesion of reduced graphene oxide (rGO) to 3D printed α-Al2O3 ceramic is 7.5 N/m. The printed graphene circuits-on-ceramics has achieved conductivity of 5.34 × 102 S m−1 after annealing at 600 °C in nitrogen atmosphere.

Labels for Eternity: Testing Printed Labels for use in Wet Collections

Abstract Will printed labels survive prolonged immersion in collection fluids, and, if so, which printing system is preferable: inkjet, laser, or thermal transfer printing? In a world with a wide variety of printers, printing substrates, and printer technologies, the interactions between them very likely affect long-term label preservation in the chemical environment of the preservation fluid. In fluid-preserved collections, the main issues frequently encountered with labels include delamination, abrasion, fading, and disintegration during immersion in solutions such as ethanol and formaldehyde aqueous solution (widely known under the commercial name formalin). Very few publications have presented testing procedures assessing the behavior and stability of printed matter immersed in the types of solvents used in fluid-based collections. This article presents a series of experiments set up at the National Natural History Collections at the Hebrew University of Jerusalem to test a variety of museum labels. The tests compared labels actually used in different natural history collections and included labels from both thermal transfer and inkjet printers. All were subjected to accelerated aging and mechanical abrasion. In our series of tests, inkjet labels gave the best performance.

Thermal inkjet bioprinting triggers the activation of the VEGF pathway in human microvascular endothelial cells in vitro

One biofabrication process that has gained tremendous momentum in the field of tissue engineering and regenerative medicine is cell-printing or most commonly bioprinting. We have shown that thermal inkjet bioprinted human microvascular endothelial cells were recruited or otherwise involved in the formation of microvasculature to form graft-host anastomoses upon implantation. The present study aims to quantify and characterize the expression and activation of specific cytokines and kinases in vitro. Morphological characteristics demonstrate elongated protrusions of TIB-HMVECs at 5–6 times the size of manually pipetted cells. Moreover, annexin V-FITC and propidium iodide apoptosis assay via flow cytometry demonstrated a 75% apoptosis among printed cells as compared to among control cells. Cell viability at a 3 d incubation period was significantly higher for printed cells as compared to control. Milliplex magnetic bead panels confirmed significant overexpression of HSP70, IL-1α, VEGF-A, IL-8, and FGF-1 of printed cells compared to control. In addition, a Human phospho-kinase array displayed a significant over activation of the heat-shock proteins HSP27 and HSP60 of printed cells compared to the manually seeded cells. Collectively, it is suggested that the massive appearance of capillary blood vessels upon implantation that has been reported elsewhere may be due to the activation of the HSP-NF-κB pathway to produce VEGF. This cell activation may be used as a new strategy for vascularization of tissue engineered constructs which are in high demand in regenerative medicine applications.

Comparison of Linear and 4-Arm Star Poly(vinyl pyrrolidone) for Aqueous Binder Jetting Additive Manufacturing of Personalized Dosage Tablets

Fabrication of personalized dosage oral pharmaceuticals using additive manufacturing (AM) provides patients with customizable, locally manufactured, and cost-efficient tablets, while reducing the probability of side effects. Binder jetting AM has potential for fabrication of customized dosage tablets, but the resulting products lack in strength due to solely relying on the binder to produce structural integrity. The selection of polymeric binders is also limited due to viscosity restraints, which limits molecular weight and concentration. To investigate and ameliorate these limitations, this article reports a comprehensive study of linear and 4-arm star poly(vinyl pyrrolidone) (PVP) over a range of molecular weights as polymeric binders for binder jetting AM and their effect on physical tablet properties. Formulation of varying molecular weights and concentrations of linear and 4-arm star PVP in deionized water and subsequent jetting revealed relationships between the critical overlap concentrations (C*) and jettability on binder jetting systems with thermal inkjet printheads. After printing with a commercially available ZCorp Spectrum Z510 printer with an HP11 printhead with a lactose and powdered sugar powder bed, subsequent measurement of compressive strength, compressive modulus, and porosity revealed structure-property relationships between molecular weight, polymer concentration, and linear and 4-arm star architectures with physical properties of binder jetted tablets. This study elucidated that the dominating factor to increase compressive strength of a tablet is dependent on the weight percent of the polymer in the binder, which filled interstitial voids between powder particles. Because 4-arm star polymers have lower solution viscosities compared to linear analogues at the same molecular weights, they were jettable at higher concentrations, thus producing the strongest tablets at a compressive strength of 1.2 MPa. Finally, the inclusion of an active pharmaceutical ingredient (API), acetaminophen, revealed maintenance of the tablet physical properties across 5-50 total wt % API in each tablet.

Characterization of thermal inkjet droplets jitter

Due to the randomness in the nucleation process of vapor bubbles and the instability of ink drop breakup in the thermal inkjet drop ejector, the drop velocity varies slightly from drop to drop, such a variation is called the jitter of the droplets. Droplet jitter causes variations in drop volume, satellite drop formation, and drop placement error on the receiving substrate, which limit the high accuracy printing application for thermal inkjet. Traditionally, a multiple-exposure method is used to photograph the droplets in flight, which is unable to measure jitters of every drop due to the low sampling rate. In this study, a laser-based high-speed flying drop measurement system is used to study the jitter. We tentatively propose a simple model to explain the cause of droplet jitter, which is related to the latency phenomenon, the randomness in droplet formation and the difference in droplets velocity. The jitter is recorded under different driving conditions and the distribution of jitter is analyzed. As a conclusion, the conditions for operation to achieve lower jitter are determined. Under certain driving conditions, the jitter can be reduced by 90%.

Numerical study of a bubble driven micromixer based on thermal inkjet technology

The Editor and publisher have retracted “Numerical study of a bubble driven micromixer based on thermal inkjet technology” Phys. Fluids 31, 062006 (2019)]. Due to a legal issue related to the publication of work covered under a confidentiality agreement, the electronic version of the paper has been removed from the website.