Manufacturing Feasibility Research Articles

Effects of Bottom Channel Coverage Ratio on Leakage Current and Static Power Consumption of Vertically Stacked GAA Si NS FETs

Abstract The performance of vertically stacked gate-all-around silicon nanosheet (GAA Si NS) field-effect transistors (FETs) is significantly impacted by the non-ideal characteristics of the bottom channel, primarily due to etching process limitations. These issues lead to variations in the coverage ratio of the bottom channel, which impacts key device characteristics like leakage current and static power consumption. In this study, we used experimentally calibrated 3-D device simulations to analyze the effects of varying bottom channel coverage ratios from 60% to 100% on the GAA Si NS n-/p-type FETs for sub-2-nm technology nodes. Our results reveal an inverse relationship between the coverage ratio and leakage current and static power consumption. Notably, n-/p-type devices at 60% bottom channel coverage ratio exhibiting leakage currents 75.6 and 102.7 times higher than those with 100% bottom channel coverage ratio. This increase is linked to substantial variations in the off-state conduction (18.5%, 75 meV for n-type FETs) and valance (15.3%, 57 meV for p-type FETs) band energies. An 80% bottom channel coverage ratio proves to be an effective compromise, reducing parasitic leakage while addressing manufacturing feasibility. However, achieving a 100% bottom channel coverage ratio remains a critical challenge, highlighting the need for further research on fabrication optimization.

From Crop Residue to Corrugated Core Sandwich Panels as a Building Material.

This study explores the potential of using underutilized materials from agricultural and forestry systems, such as rice husk, wheat straw, and wood strands, in developing corrugated core sandwich panels as a structural building material. By leveraging the unique properties of these biobased materials within a corrugated geometry, the research presents a novel approach to enhancing the structural performance of such underutilized biobased materials. These biobased materials were used in different lengths to consider the manufacturing feasibility of corrugated panels and the effect of fiber length on their structural performance. The average lengths for wood strands and wheat straws were 12-15 cm and 3-7.5 cm, respectively, while rice husks were like particles, about 7 mm long. Due to the high silica content in rice husk and wheat straw, which negatively impacts the bonding performance, polymeric diphenylmethane diisocyanate (pMDI), an effective adhesive for such materials, was used for the fabrication of corrugated panels. Wood strands and phenol formaldehyde (PF) adhesive were used to fabricate flat outer layers. Flat panels were bonded to both sides of the corrugated panels using a polyurethane adhesive to develop corrugated core sandwich panels. Four-point bending tests were conducted to evaluate the panel's bending stiffness, load-carrying capacity, and failure modes. Results demonstrated that sandwich panels with wood strand corrugated cores exhibited the highest bending stiffness and load-bearing capacity, while those with wheat straw corrugated cores performed similarly. Rice husk corrugated core sandwich panels showed the lowest mechanical performance compared to other sandwich panels. Considering the applications of these sandwich panels as floor, wall, and roof sheathing, all these panels exhibited superior bending performance compared to 11.2 mm- and 17.42 mm-thick commercial OSB (oriented strand board) panels, which are commonly used as building materials. These sandwich structures supported a longer span than commercial OSB panels while satisfying the deflection limit of L/360. The findings suggest the transformative potential of converting renewable yet underutilized materials into an engineered concept, corrugated geometry, leading to the development of high-performance, carbon-negative building materials suitable for flooring and roof applications.

In situ embedding of resistance temperature detectors with the use of laser-foil-printing additive manufacturing

Abstract Additive manufacturing (AM) allows sensor embedding with the freedom of geometry flexibility. This research aims to experimentally determine the viability of integrating Platinum resistance temperature detectors into AM 304L stainless steel parts using laser foil printing (LFP) for real-time measurement applications. Using metal foils as a feedstock in LFP provides higher conductivity and faster cooling rate resulting in higher strength compared to powder-bed AM. However, one of the common challenges during the laser aided metal AM processes is that the heat accumulation can damage the embedded sensor. This study uses spot pattern welding processing strategy to mitigate these process-related risks by minimizing the melt pool volume during the layered fabrication process. High-temperature resistant ceramic adhesives are employed to fill the gap, and to create a conductive interface between the feedstock and the sensor. After curing the ceramic adhesives, in situ temperature measurement data are collected to investigate the success of the sensor embedding process. This work demonstrates the feasibility for LFP smart manufacturing, offering the potential for component embedding and an advanced real-time monitoring system.

Preparation and mechanical properties of 316L-Ti composites by Laser Powder Bed Fusion

Abstract To investigate the feasibility of additive manufacturing of energetic structural materials, this study fabricated 316L-Ti composites using Laser Powder Bed Fusion. The research examined the forming process parameters of 316L-Ti and analyzed the changes in relative density, defects, phases, and mechanical properties of the composites with varying laser energy densities. The results indicate that the primary defects in 316L-Ti composite samples are delamination and lack of fusion (LoF) pores. At high laser energy densities, delamination cracks are likely to occur, leading to significant delamination, warping, and even failure to form the samples. Conversely, at low laser energy densities, samples show minimal delamination but an increase LoF pores, leading to worsened mechanical properties. The addition of titanium results in the presence of both austenite and ferrite phases. Optimal results are achieved at a laser energy density of 120 W and a scanning rate of 1200 mm/s, yielding samples with minimal defects, achieving a density of 91.69% of the theoretical value, and demonstrating a compressive strength of 1191 MPa.

Automated production of nerve repair constructs containing endothelial cell tube-like structures

Engineered neural tissue (EngNT) is a stabilised aligned cellular hydrogel that offers a potential alternative to the nerve autograft for the treatment of severe peripheral nerve injury. This work aimed to automate the production of EngNT, to improve the feasibility of scalable manufacture for clinical translation. Endothelial cells were used as the cellular component of the EngNT, with the formation of endothelial cell tube-like structures mimicking the polarised vascular structures formed early on in the natural regenerative process. Gel aspiration-ejection for the production of EngNT was automated by integrating a syringe pump with a robotic positioning system, using software coded in Python to control both devices. Having established the production method and tested mechanical properties, the EngNT containing human umbilical vein endothelial cells (EngNT-HUVEC) was characterised in terms of viability and alignment, compatibility with neurite outgrowth from rat dorsal root ganglion neurons and formation of endothelial cell networksin vitro. EngNT-HUVEC manufactured using the automated system contained viable and aligned endothelial cells, which developed into a network of multinucleated endothelial cell tube-like structures inside the constructs and an outer layer of endothelialisation. The EngNT-HUVEC constructs were made in various sizes within minutes. Constructs provided support and guidance to regenerating neuritesin vitro. This work automated the formation of EngNT, facilitating high throughput manufacture at scale. The formation of endothelial cell tube-like structures within stabilised hydrogels provides an engineered tissue with potential for use in nerve repair.

Emerging trends and innovations in all-solid-state lithium batteries: A comprehensive review

All-solid-state lithium batteries, which utilize solid electrolytes, are regarded as the next generation of energy storage devices. Recent breakthroughs in this type of rechargeable battery have significantly accelerated their path towards becoming commercially viable. Nevertheless, the development of such devices is impeded by various obstacles, including limitations in ion transfer capability, interfacial hurdles, and chemical and electrochemical stability. This paper provides a comprehensive review of the latest advancements in all-solid-state lithium-based batteries. The main emphasis is on the fabrication techniques, novel solid electrolytes, and the application of advanced cathode and anode materials to expedite research and development in this field. Moreover, the feasibility of large-scale manufacturing of solid-state batteries has been evaluated. Finally, the most practical and effective approaches for the advancement of these batteries have been proposed and examined.

Isogeometric proportional topology optimization (IGA-PTO) for multi-material problems

This study addresses the multi-material optimization problem by the effective and robust isogeometric proportional topology optimization (IGA-PTO) approach. Non-uniform rational B-spline basis functions are used for descriptions of geometry, displacement field, and density fields of material phases. The alternating active-phase algorithm is employed to convert the optimization problem with multiple constraints into a series of sub-problems of single constraint. Several examples are exhibited, and intensive comparisons with the gradient-based optimality criteria (OC) algorithm are presented to highlight the superior performance of the proposed PTO algorithm. Finally, the optimized topologies are prototyped using 3D printing technology to evidence the manufacturing feasibility.

Survey of Microstructures and Dimensional Accuracy of Various Microlattice Designs Using Additively Manufactured 718 Superalloy.

Microlattices hold significant potential for developing lightweight structures for the aeronautics and astronautics industries. Laser Powder Bed Fusion (LPBF) is an attractive method for producing these structures due to its capacity for achieving high-resolution, intricately designed architectures. However, defects, such as cracks, in the as-printed alloys degrade mechanical properties, particularly tensile strength, and thereby limit their applications. This study examines the effects of microlattice architecture and relative density on crack formation in the as-printed 718 superalloy. Complex microlattice design and higher relative density are more prone to large-scale crack formation. The mechanisms behind these phenomena are discussed. This study reveals that microlattice type and relative density are crucial factors in defect formation in LPBF metallic alloys. The transmission electron microscopy observations show roughly round γ″ precipitates with an average size of 10 nm in the as-printed 718 without heat treatment. This work demonstrates the feasibility of the additive manufacturing of complex microlattices using 718 superalloys towards architectured lightweight structures.

Investigation of bending and crush behaviors in polymer lattice structures: Computational approaches and experimental evaluation

This paper aims to evaluate the manufacturing feasibility of using Fused Deposition Modeling (FDM) 3D printing for creating complex lattice structures and exploring the mechanical properties of various lattice designs, focusing on bending and compression behaviors. The comparison centers on the results of bending rigidity and energy absorption capacity, intending to be obtained from simulation and practical outcomes. The research addresses challenges related to achieving consistent mass across lattice structures due to manufacturing parameters. Discrepancies in flexural rigidity and compression behavior among the produced models trigger an exploration into the influence of design factors. The study reveals significant insights into the mechanical properties of six complex lattice structures produced through FDM 3D printing. The Tetrahedron-Cubic lattice stands out with superior bending rigidity at 15.36 N/mm, and variations in performance are attributed to layer orientation and material anisotropy. Specific energy absorption reaches its peak in the Tetrahedron-Cubic lattice at 38.54 J/g. These conclusive results provide considerations for future design and optimization. Through a focus on simplicity, intricacy, and unique geometry, the study effectively tackles manufacturing challenges and resolves discrepancies between experimental tests and simulations.

Laboratory and field validation of the performance benefits and costs of thin triple-pane windows in residential buildings

The adoption of high-performance triple-pane windows that significantly reduce heat transfer has been slow, in part because they are thicker, heavier, and more costly than double-pane windows. One path to increase adoption of triple-pane windows is to replace the conventional double-glazing insulated glass unit (IGU) with a modified triple-glazing design that uses a very thin central pane of glass. This thinner triple-pane IGU can then be “dropped in” to the double-pane IGU pocket without requiring major modifications to frame design. The Department of Energy sponsored laboratory and field testing of thin triple-pane windows by Pacific Northwest National Laboratory. This article presents findings from both the Lab Homes study and subsequent field demonstrations carried out over a 3-year period (2020–2023). The laboratory and field studies demonstrated the manufacturing and distribution feasibility of thin triple-pane windows, successfully installed at multiple sites, using double-pane frames from four different manufacturers and thin triple-pane IGUs from two different manufacturers. Compared to a home with double-pane, clear-glass windows, testing demonstrated average whole-home heating energy savings of 12% and cooling energy savings of 27% for thin triple-pane windows. Improvements in comfort, sound insulation, and condensation potential were noted in both laboratory and field studies.

Design and simulation of a compact polarization beam splitter based on dual-core photonic crystal fiber with elliptical gold layer

For the polarization multiplexing requirements in all-optical networks, this work presents a compact all-fiber polarization beam splitter (PBS) based on dual-core photonic crystal fiber (PCF) and an elliptical gold layer. Numerical analysis using the finite element method (FEM) demonstrates that the mode modulation effect of the central gold layer effectively reduces the dimensions of the proposed PBS. By determining reasonable structural parameters of the proposed PCF, the coupling length ratio (CLR) between X- and Y-polarized super-modes can approach 2, achieving a minimal device length of 0.122 mm. The PBS exhibits a maximum extinction ratio (ER) of − 65 dB at 1.55 μm, with an operating bandwidth spanning 100 nm (1.5–1.6 μm) and a stable insertion loss (IL) of ~ 1.5 dB at 1.55 μm. Furthermore, the manufacture feasibility and performance verification scheme are also investigated. It is widely anticipated that the designed PBS will play a crucial role in the ongoing development process of miniaturization and integration of photonic devices.

FreeArcs Knife: a Novel Stereotactic Radiosurgery System

This paper describes the design of an innovative linear accelerator image-guided radiosurgery (IGRS) device, which is based on a composite twofold rotary gantry structure. The paper discusses five aspects of the innovative device: its overall composition, the safety net space created by the accelerator radiation head as it rotates around the patient's longitudinal axis, the non-coplanar spherical coverage in the direction of the incidence angle for quasi-4π delivery, the structural features of the composite twofold rotary gantry, and the processes of treatment planning and implementation. It elaborates on the device's manufacturing feasibility, safety, effectiveness, accuracy, and efficiency. The conclusion is that this innovative device design holds significant development value and market promotion potential.

Biopolymeric Insulin Membranes for Antimicrobial, Antioxidant, and Wound Healing Applications.

Delayed wound healing increases the wound's vulnerability to possible infections, which may have lethal outcomes. The treatments available can be effective, but the urgency is not fully encompassed. The drug repositioning strategy proposes effective alternatives for enhancing medical therapies for chronic diseases. Likewise, applying wound dressings as biodegradable membranes is extremely attractive due to their ease of application, therapeutic effectiveness, and feasibility in industrial manufacturing. This article aims to demonstrate the pleiotropic effects during insulin repositioning in wound closure by employing a biopolymeric membrane-type formulation with insulin. We prepared biopolymeric membranes with sodium alginate cross-linked with calcium chloride, supported in a mixture of xanthan gum and guar gum, and plasticized with glycerol and sorbitol. Human insulin was combined with poloxamer 188 as a protein stabilizing agent. Our investigation encompassed physicochemical and mechanical characterization, antioxidant and biological activity through antibacterial tests, cell viability assessments, and scratch assays as an in vitro and in vivo wound model. We demonstrated that our biopolymeric insulin membranes exhibited adequate manipulation and suitable mechanical resistance, transparency, high swelling capability (1100%), and 30% antioxidant activity. Furthermore, they exhibited antibacterial activity (growth inhibition of S. aureus at 85% and P. aeruginosa at 75%, respectively), and insulin promoted wound closure in vitro with a 5.5-fold increase and 72% closure at 24 h. Also, insulin promoted in vivo wound closure with a 3.2-fold increase and 92% closure at 10 days compared with the groups without insulin, and this is the first report that demonstrates this therapeutic effect with two administrations of 0.7 IU. In conclusion, we developed a multifunctional insulin-loaded biopolymeric membrane in this study, with the main activity derived from insulin's role in wound closure and antioxidant activity, augmented by the antimicrobial effect attributed to the polymer poloxamer 188. The synergistic combination of excipients enhances its usefulness and highlights our innovation as a promising material in wound healing materials.

Machine learning–enabled direct ink writing of conductive polymer composites for enhanced performance in thermal management and current protection

This study introduces a novel approach that leverages the synergy of machine learning (ML) and Direct Ink Writing (DIW) to optimize the manufacturing feasibility of conductive polymer composites (CPCs) films. The main research focus centers on precisely fine-tuning the printing parameters to strike the perfect balance between the high loading of dendritic copper fillers and their influences on processing and composite performance properties. This pioneering combination significantly enhances the precision of the final product without resorting to time-consuming procedures. ML algorithms contributed to identifying optimal printing variables such as speed, flow pressure, and filler concentration, which helped in identifying the optimal filler content and its performance capabilities. The resulting films exhibited thermo-resistive behavior with a noticeable resistivity increase by 6-7 orders of magnitude at elevated temperatures, specifically around 100 °C. Furthermore, the study highlights remarkable strain-sensing capabilities, simultaneously showcasing a substantial increase in composite modulus. These discoveries bear substantial significance for the development of exceptionally functional thermal interface materials suitable for use in sensors, current collectors, and energy storage devices. The method presented here offers a promising pathway for advancing the fabrication and performance optimization of conductive polymer composites, opening up diverse applications in emerging technologies.

Polyester and Hymenaea Courbaril Residue for Sustainable Composite Manufacturing

Objective: To evaluate the mechanical behavior of polymer composites reinforced by wood residue known as Játobá (Hymenaea Courbaril), in powder form. It aims to reduce impacts to the environment through the use of waste. Theoretical Framework: Composites are generated from the union of materials, aiming to obtain specific properties arising from their components. Usually these are divided into two phases, matrix. The possibility of using materials less harmful to the environment in composite has gained prominence in research in the area. Method: To obtain the properties of the composites, standardized specimens were manufactured according to ASTM D638. The matrix selected was terephthalic polyester resin and the reinforcement was Játobá wood residue, in the form of powder. The results were obtained by tensile strength tests. Results and Discussion: The average value of tensile strength obtained was 11.76 (±1.70) MPa. The comparison of the results of this study with other literature revealed the superiority of the tensile strength of the composite of the present work in relation to others with different reinforcements of wood residues. Research Implications: The use of wood waste in composites is beneficial for reducing the irregular disposal of matter in the environment. Also, it aims to generate added value to a useless material. Originality/Value: The use of natural and renewable materials as reinforcement in composites is of great relevance, aiming to reduce the use of synthetic raw material. In addition, there is the manufacture of composites of low cost and weight and feasibility of manufacture.

Evaluation of Additive Manufacturing Feasibility in the Energy Sector: A Case Study of a Gas-Insulated High-Voltage Switchgear

Evaluation of Additive Manufacturing Feasibility in the Energy Sector: A Case Study of a Gas-Insulated High-Voltage Switchgear

Polyester and Hymenaea Courbaril Residue for Sustainable Composite Manufacturing

Objective: To evaluate the mechanical behavior of polymer composites reinforced by wood residue known as Játobá (Hymenaea Courbaril), in powder form. It aims to reduce impacts to the environment through the use of waste. Theoretical Framework: Composites are generated from the union of materials, aiming to obtain specific properties arising from their components. Usually these are divided into two phases, matrix. The possibility of using materials less harmful to the environment in composite has gained prominence in research in the area. Method: To obtain the properties of the composites, standardized specimens were manufactured according to ASTM D638. The matrix selected was terephthalic polyester resin and the reinforcement was Játobá wood residue, in the form of powder. The results were obtained by tensile strength tests. Results and Discussion: The average value of tensile strength obtained was 11.76 (±1.70) MPa. The comparison of the results of this study with other literature revealed the superiority of the tensile strength of the composite of the present work in relation to others with different reinforcements of wood residues. Research Implications: The use of wood waste in composites is beneficial for reducing the irregular disposal of matter in the environment. Also, it aims to generate added value to a useless material. Originality/Value: The use of natural and renewable materials as reinforcement in composites is of great relevance, aiming to reduce the use of synthetic raw material. In addition, there is the manufacture of composites of low cost and weight and feasibility of manufacture.

Rapidly-manufactured CD276 CAR-T cells exhibit enhanced persistence and efficacy in pancreatic cancer

BackgroundPancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer.MethodsIn the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T.ResultsWe found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48–72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal.ConclusionsIn this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.

DIPG-47. SEQUENTIAL INTRAVENOUS AND INTRACEREBROVENTRICULAR GD2-CAR T-CELL THERAPY FOR H3K27M-MUTATED DIFFUSE MIDLINE GLIOMAS

Abstract BACKGROUND H3K27M-mutant diffuse midline gliomas (DMGs) express uniformly high levels of the GD2 disialoganglioside. In preclinical models, chimeric antigen receptor modified T-cells (CAR T-cells) targeting GD2 robustly regressed orthotopically xenografted DMGs. METHODS This Phase I trial (NCT04196413) administered one IV dose of autologous T-cells transduced with a GD2-CAR retroviral vector to patients with H3K27M-mutant pontine (DIPG) or spinal (sDMG) diffuse midline gliomas at two dose levels (DL1=1e6 GD2-CAR T-cells/kg; DL2=3e6 GD2-CAR T-cells/kg) following standard lymphodepleting (LD) chemotherapy. Patients with clinical or imaging benefit following IV infusion were eligible for subsequent intracerebroventricular (ICV) GD2-CAR T-cell infusions (10-30e6 GD2-CAR T-cells). Primary objectives were to determine feasibility of manufacturing, assess tolerability of IV GD2-CAR T-cells in patients with DIPG and sDMG, and identify a maximally tolerated dose of IV GD2-CAR T-cells following lymphodepleting chemotherapy. Secondary objectives included preliminary assessments of benefit. Here we report the final results of Arm A. RESULTS Thirteen patients enrolled and 11 received one IV GD2-CAR T infusion on study [n=3 DL1(3 DIPG); n=8 DL2(6 DIPG/2 sDMG). GD2-CAR T-cells were successfully manufactured for each patient. After IV infusion, no dose-limiting toxicities (DLTs) occurred on DL1, but three patients experienced DLT on DL2 due to grade 4 cytokine release syndrome (CRS). Nine patients received ICV infusions, which were not associated with DLTs. All patients exhibited tumor inflammation-associated neurotoxicity (TIAN). Four patients demonstrated major volumetric reductions of 52%, 54%, 91% and 100%. One patient exhibited a complete response durable for >30 months since therapy began. Eight patients demonstrated neurological benefit based upon a protocol-directed Clinical Improvement Score. CONCLUSIONS Sequential IV followed by ICV GD2-CAR T-cells infusions induced tumor regressions and neurological improvements. DL1 was established as the maximally tolerated IV GD2-CAR T-cell dose. Neurotoxicity was safely managed with intensive monitoring and close adherence to a management algorithm.

A phase 1, first-in-human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2-overexpressing solid tumors.

TPS2682 Background: Myeloid cells are actively recruited to the solid tumor microenvironment (TME) and have the potential to mediate tumor control via phagocytosis, TME remodeling, and T cell activation. We previously developed human chimeric antigen receptor macrophages (CAR-M) and have shown potent anti-tumor activity in pre-clinical solid tumor models. The anti-HER2 CAR-M cell therapy product, CT-0508, is currently being evaluated in a Phase I trial as a monotherapy and in combination with pembrolizumab. Early clinical data have shown feasibility, safety, and validated the mechanism of action. We have developed a next-generation CAR monocyte (CAR-Mono) platform to increase the dose, improve tumor trafficking and engraftment, and shorten the manufacturing and vein-to-vein time as compared to CAR-M therapy. CT-0525 is an autologous anti-HER2 CAR-Mono cell therapy based on CD14+ monocytes engineered with an Ad5f35 adenoviral vector to express an anti-HER2 CAR. Pre-clinical studies have demonstrated the feasibility, phenotype, pharmacokinetics, durable CAR expression, cellular fate, antigen specificity, and anti-tumor activity of CT-0525. Pre-clinical studies have shown that CT-0525 differentiated into pro-inflammatory CAR-M in vivo and controlled tumor growth. The CT-0525 manufacturing process takes one day and enables the production of up to 10 billion cells from a single apheresis. CT-0525 is being investigated in a first-in-human, open-label, multi-center, Phase I study in patients with HER2 overexpressing solid tumors. Methods: This Phase 1, first-in-human study evaluates the feasibility, safety, tolerability, trafficking, TME activation, and preliminary evidence of efficacy of the investigational CAR-Mono product CT-0525 in 6 participants (pts) with locally advanced unresectable/metastatic solid tumors overexpressing HER2. Pts previously treated with anti-HER2 therapies are eligible. Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation. The 1st cohort of pts (n=3) will receive 3 x 109 CT-0525 CAR positive monocytes administered IV in one infusion. If tolerated as per the modified toxicity probability interval algorithm (mTPI), the 2nd cohort of pts (n=3) will receive up to 10 x 109 CT-0525 CAR positive monocytes in one infusion. CT-0525 will be administered without conditioning chemotherapy. Primary endpoints include assessment of safety and tolerability, as well as manufacture feasibility. Correlative assessments include pre- and post-treatment biopsies and blood samples for safety, immunogenicity, pharmacokinetics, tumor trafficking, TME modulation, epitope spreading, and other translational biomarkers. Clinical trial information: NCT06254807 .