In vivo manufacture and manipulation of CAR-T cells for better druggability.

The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs. This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved. Moreover, the on-off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products.

Self-Driven, Monopolar Electrohydrodynamic Printing via Dielectric Nanoparticle Layer.

Electrohydrodynamic printing holds both ultrahigh-resolution fabrication capability and unmatched ink-viscosity compatibility yet fails on highly insulating thick/irregular substrates. Herein, we proposed a single-potential driven electrohydrodynamic printing process with submicrometer resolution on arbitrary nonconductive targets, regardless of their geometric shape or sizes, via precoating with an ultrathin dielectric nanoparticle layer. Benefiting from the favorable Maxwell-Wagner polarization, the reversely polarized spot brought about a significant drop (∼57% for ceramics) in the operation voltage as its induced electric field and a negligible residual charge accumulation. Thus, ordered micro/nanostructures with line widths down to 300 nm were directly written at a stage speed as low as 5 mm/s, and silver features with width of ∼2 µm or interval of ∼4 µm were achieved on insulating substrates separately. Flexible sensors and curved heaters were then high-precision printed and demonstrated successfully, presenting this technique with huge potential for fabricating flexible/conformal electronics on arbitrary 3D structures.

Ultra-Durable Polysilicon Based Tribovoltaic Nanogenerators for Bearing In Situ Rotational Speed Sensing.

Tribovoltaic nanogenerator (TVNG) is an emerging energy device with the advantages of direct current and high power density. At present, many TVNGs are based on single-crystal materials, which are expensive and fragile during structural processing. Here, a polysilicon-based TVNG for bearing in situ rotational speed sensing is developed, which has the same level of performance and lower cost compared to monocrystalline silicon. The defects in polysilicon can provide additional carriers, but the grain boundaries can suppress the transport process of carriers, resulting in almost the same electrical output as single crystals. The oiled sliding mode TVNG has an impressive durability of up to 1 million cycles. The friction coefficient of rolling mode TVNG is as low as 0.14. Based on rolling mode polysilicon TVNG, the tapered roller bearing, thrust ball bearing, and deep groove ball bearing are manufactured by cutting and engraving processes. Moreover, their short-circuit current and open-circuit voltage are linear with speed, and the fitting coefficient is as high as 0.99, providing favorable conditions for in situ rotational speed sensing. This work presents a structure-function integrated bearing design methodology, demonstrating the considerable potential of in situ sensing for intelligent components in the industrial Internet of Things.

Human platelet lysate enhances in vivo activity of CAR-Vδ2 T cells by reducing cellular senescence and apoptosis.

BACKGROUND AIMS: Vγ9Vδ2 T cells are an attractive cell platform for the off-the-shelf cancer immunotherapy as the result of their lack of alloreactivity and inherent multi-pronged cytotoxicity, which could be further amplified with chimeric antigen receptors (CARs). In this study, we sought to enhance the in vivo longevity of CAR-Vδ2 T cells by modulating ex vivo manufacturing conditions and selecting an optimal CAR costimulatory domain. METHODS: Specifically, we compared the anti-tumor activity of Vδ2 T cells expressing anti-CD19 CARs with costimulatory endodomains derived from CD28, 4-1BB or CD27 and generated in either standard fetal bovine serum (FBS)- or human platelet lysate (HPL)-supplemented medium. RESULTS: We found that HPL supported greater expansion of CAR-Vδ2 T cells with comparable in vitro cytotoxicity and cytokine secretion to FBS-expanded CAR-Vδ2 T cells. HPL-expanded CAR-Vδ2 T cells showed enhanced in vivo anti-tumor activity with longer T-cell persistence compared with FBS counterparts, with 4-1BB costimulated CAR showing the greatest activity. Mechanistically, HPL-expanded CAR Vδ2 T cells exhibited reduced apoptosis and senescence transcriptional pathways compared to FBS-expanded CAR-Vδ2 T cells and increased telomerase activity. CONCLUSIONS: This study supports enhancement of therapeutic potency of CAR-Vδ2 T cells through a manufacturing improvement.

Scalable manufacture of therapeutic mesenchymal stromal cell products on customizable microcarriers in vertical wheel bioreactors that improve direct visualization, product harvest, and cost.

BACKGROUND AIMS: Human mesenchymal stromal cells (hMSCs) and their secreted products show great promise for treatment of musculoskeletal injury and inflammatory or immune diseases. However, the path to clinical utilization is hampered by donor-tissue variation and the inability to manufacture clinically relevant yields of cells or their products in a cost-effective manner. Previously we described a method to produce chemically and mechanically customizable gelatin methacryloyl (GelMA) microcarriers for culture of hMSCs. Herein, we demonstrate scalable GelMA microcarrier-mediated expansion of induced pluripotent stem cell (iPSC)-derived hMSCs (ihMSCs) in 500 mL and 3L vertical wheel bioreactors, offering several advantages over conventional microcarrier and monolayer-based expansion strategies. METHODS: Human mesenchymal stromal cells derived from induced pluripotent cells were cultured on custom-made spherical gelatin methacryloyl microcarriers in single-use vertical wheel bioreactors (PBS Biotech). Cell-laden microcarriers were visualized using confocal microscopy and elastic light scattering methodologies. Cells were assayed for viability and differentiation potential in vitro by standard methods. Osteogenic cell matrix derived from cells was tested in vitro for osteogenic healing using a rodent calvarial defect assay. Immune modulation was assayed with an in vivo peritonitis model using Zymozan A. RESULTS: The optical properties of GelMA microcarriers permit noninvasive visualization of cells with elastic light scattering modalities, and harvest of product is streamlined by microcarrier digestion. At volumes above 500 mL, the process is significantly more cost-effective than monolayer culture. Osteogenic cell matrix derived from ihMSCs expanded on GelMA microcarriers exhibited enhanced in vivo bone regenerative capacity when compared to bone morphogenic protein 2, and the ihMSCs exhibited superior immunosuppressive properties in vivo when compared to monolayer-generated ihMSCs. CONCLUSIONS: These results indicate that the cell expansion strategy described here represents a superior approach for efficient generation, monitoring and harvest of therapeutic MSCs and their products.

Engineering an Escherichia coli based in vivo mRNA manufacturing platform.

Synthetic mRNA is currently produced in standardized in vitro transcription systems. However, this one-size-fits-all approach has associated drawbacks in supply chain shortages, high reagent costs, complex product-related impurity profiles, and limited design options for molecule-specific optimization of product yield and quality. Herein, we describe for the first time development of an in vivo mRNA manufacturing platform, utilizing an Escherichia coli cell chassis. Coordinated mRNA, DNA, cell and media engineering, primarily focussed on disrupting interactions between synthetic mRNA molecules and host cell RNA degradation machinery, increased product yields >40-fold compared to standard "unengineered" E. coli expression systems. Mechanistic dissection of cell factory performance showed that product mRNA accumulation levels approached theoretical limits, accounting for ~30% of intracellular total RNA mass, and that this was achieved via host-cell's reallocating biosynthetic capacity away from endogenous RNA and cell biomass generation activities. We demonstrate that varying sized functional mRNA molecules can be produced in this system and subsequently purified. Accordingly, this study introduces a new mRNA production technology, expanding the solution space available for mRNA manufacturing.

Hooded crows (Corvus cornix) manufacture objects relative to a mental template.

It was recently found that not only tool-specialized New Caledonian crows, but also Goffin cockatoos can manufacture physical objects in accordance with a mental template. That is, they can emulate features of existing objects when they manufacture new items. Both species spontaneously ripped pieces of card into large strips if they had previously learned that a large template was rewarded, and small strips when they previously learned that a small template was rewarded. Among New Caledonian crows, this cognitive ability was suggested as a potential mechanism underlying the transmission of natural tool designs. Here, we tested for the same ability in another non-specialised tool user-Hooded crows (Corvus cornix). Crows were exposed to pre-made template objects, varying first in colour and then in size, and were rewarded only if they chose pre-made objects that matched the template. In subsequent tests, birds were given the opportunity to manufacture versions of these objects. All three crows ripped paper pieces from the same colour material as the rewarded template, and, crucially, also manufactured objects that were more similar in size to previously rewarded, than unrewarded, templates, despite the birds being rewarded at random in both tests. Therefore, we found the ability to manufacture physical objects relative to a mental template in yet another bird species not specialized in using or making foraging tools in the wild, but with a high level of brain and cognitive development.

Adaptive Fabrication of Electrochemical Chips with a Paste-Dispensing 3D Printer.

Electrochemical (EC) detection is a powerful tool supporting simple, low-cost, and rapid analysis. Although screen printing is commonly used to mass fabricate disposable EC chips, its mask is relatively expensive. In this research, we demonstrated a method for fabricating three-electrode EC chips using 3D printing of relatively high-viscosity paste. The electrodes consisted of two layers, with carbon paste printed over silver/silver chloride paste, and the printed EC chips were baked at 70 °C for 1 h. Engineering challenges such as bulging of the tubing, clogging of the nozzle, dripping, and local accumulation of paste were solved by material selection for the tube and nozzle, and process optimization in 3D printing. The EC chips demonstrated good reversibility in redox reactions through cyclic voltammetry tests, and reliably detected heavy metal ions Pb(II) and Cd(II) in solutions using differential pulse anodic stripping voltammetry measurements. The results indicate that by optimizing the 3D printing of paste, EC chips can be obtained by maskless and flexible 3D printing techniques in lieu of screen printing.

Digital Surgical Guides in Mandibular Genioplasty: Evaluating Precision Against Conventional Techniques.

BACKGROUND: Mandibular genioplasty, a central procedure in oral and maxillofacial surgery, has traditionally relied on surgeon experience with potential limitations in precision. The advent of digital methods, particularly computer-aided design/computer-aided manufacturing (CAD/CAM), offers a promising alternative. This study aims to evaluate the efficacy of digital surgical guides in improving the precision of mandibular genioplasty. METHODS: A prospective analysis of 50 patients undergoing genioplasty was performed, 30 in the experimental group using digital surgical guides and 20 in the control group using traditional methods. Three-dimensional reconstructions were obtained using cone-beam computed tomography (CBCT) and digital scans. Osteotomy guides were 3D-printed based on group assignment. Postoperatively, accuracy was assessed by measuring distances between landmarks. RESULTS: The experimental group showed significantly reduced horizontal positioning errors in genioplasty advancement, with no significant differences in vertical errors. For genioplasty retraction, the experimental group showed fewer vertical positioning errors, while horizontal errors remained consistent. CONCLUSIONS: The use of digital surgical guides in mandibular genioplasty significantly improves surgical accuracy, resulting in improved outcomes and patient satisfaction. This study highlights the potential of digital methods in refining oral and maxillofacial surgical procedures. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Effect of Thermo-mechanical Cycling on Fracture Resistance of Different CAD/CAM Crowns: An In Vitro Study.

AIM: To evaluate the effect of thermo-mechanical cycling (TMC) on fracture resistance of different computer-aided design/computer-aided manufacture (CAD/CAM) crowns. MATERIALS AND METHODS: A total of 42 CAD/CAM crowns were fabricated on epoxy resin maxillary first premolar teeth and divided into three groups (n = 14) according to the material used: IPS e.max CAD (Ivoclar Vivadent) lithium disilicate (LD), Vita ENAMIC (VE) (VITA Zahnfabrik), Tetric CAD (Ivoclar Vivadent). Also, each group was subdivided into two equal subgroups according to TMC (n = 7). Subgroups (O) without TMC and subgroup (W) with TMC (5-55°C, 30 second, 75,000 cycles). All samples in each group were cemented with a universal bond (Tetric N bond universal) and adhesive resin cement (Variolink Esthetic DC) (Ivoclar Vivadent). Subsequently, the samples were loaded to failure in a universal testing machine at a crosshead speed of 1 mm/min, and the fracture pattern and the fracture resistance in each group were recorded. RESULTS: Fracture resistance was analyzed by one-way analysis of variance (ANOVA) test, followed by Tukey's post hoc test for pairwise comparison. Fracture resistance showed a significant difference between the tested groups before and after TMC; IPS e.max CAD has the highest value (1233.35 ± 97.72, 1165.73 ± 199.54 N) followed by Tetric CAD (927.62 ± 42.5, 992.04 ± 53.46 N) and Vita ENAMIC has lowest value (506.49 ± 74.24, 354.69 ± 90.36 N). CONCLUSION: Thermo-mechanical cycling affected the fracture resistance of both polymer-based CAD/CAM crowns. CLINICAL SIGNIFICANCE: For dental practitioners, both IPS e.max CAD and Tetric CAD can be used clinically for posterior teeth, providing satisfactory results and resistance to fracture. How to cite this article: Elmokadem MI, Haggag KM, Mohamed HR. Effect of Thermo-mechanical Cycling on Fracture Resistance of Different CAD/CAM Crowns: An In Vitro Study. J Contemp Dent Pract 2024;25(1):29-34.

Strengths and weaknesses of current and future prospects of artificial intelligence-mounted technologies applied in the development of pharmaceutical products and services.

Starting from drug discovery, through research and development, to clinical trials and FDA approval, artificial intelligence (AI) plays a vital role in planning, developing, assessing modelling, and optimization of product attributes. In recent decades, machine-learning algorithms integrated into artificial neural networks, neuro-fuzzy logic and decision trees have been applied to tremendous domains related to drug formulation development. Optimized formulations were transformed from lab to market based on optimized properties derived from AI Technologies. Research and development in pharmaceutical industry rely upon computer-driven equipment and machine learning technology to extract data, perform simulations, modelling, and optimization to get optimum solutions. Merging AI technologies in various steps of pharmaceutical manufacture is a major challenge due to lack of in-house technologies. In silico studies based on artificial intelligence are widely applied as effective tools to screen the market needs of medications and pharmaceutical services through inspecting scientific literature and prioritizing medicines for specific illnesses or a particular patient. Specialized personnel who excel in scientific and data science with analytical knowledge are essential for transformation to smart manufacturing and offering services. However, privacy, cybersecurity, AI-dependent unemployment, and ownership rights of AI technologies require proper regulations to gain the benefits and minimize the drawbacks.

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With the increasing maturity and popularization of digital technology in oral medicine, its application has now expanded to various clinical subspecialties of oral medicine. Digitalization has become one of the important development directions of oral medicine. What is the current development status of digital technology in oral medicine? In what ways is digital technology applied across various clinical specialties of oral medicine? Dentists are particularly concerned about these issues in their clinical work and research. In this paper, all the digital technologies applied in oral medicine are organized and categorized from a technical perspective. In this paper, we focused on presenting three-dimensional data acquisition technology, dental computer-aided design technology, dental computer-aided processing technology, and oral surgery implementation technology. Their technical principles, technical characteristics, applications in oral medicine, a secondary discipline of medicine, and the development status of domestically-developed technology are described and reviewed in detail. The other technologies such as oral digital materials, oral virtual simulation teaching, and oral multi-source data management are briefly discussed. We intend to provide references for dentists to apply digital technology in clinical practice and research.

Microfluidic Precision Manufacture of High Performance Liquid Chromatographic Microspheres.

A key bottleneck in developing chromatographic material is the chemically entangled control of morphology, pore structure, and material chemistry, which holds back precision material manufacture in order to pursue advanced separation performance. In this work, a precision manufacture strategy based on droplet microfluidics was developed, for production of highly efficient chromatographic microspheres with independent control over particle morphology, pore structure and material chemistry. The droplet-synthesized microspheres display extremely narrow particle size distribution (CV<3%), enabling a 100% production yield due to complete elimination of sieving steps. More importantly, the size of the droplet-synthesized microspheres is freely adjustable without the need for re-optimizing chemical recipes or reaction conditions. The resulting materials exhibit excellent separation efficiencies, achieving a reduced plate height of hmin​=1.67. This precision manufacture strategy also allows for flexible pore design and continuous pore size adjustment across three orders of magnitudes, providing a novel vehicle for resolution fine-tuning targeting protein separation. Besides traditional silica, organic-inorganic hybrid silica, zirconia, and titania microspheres can also be precisely synthesized on the same platform, supporting various separation applications and operating conditions. Powered by precision manufacture, super-throughput production, and versatile chemistry, the high-performance droplet-synthesized separation material will pave the way towards green and precision chromatographic industry.

Individual preferences for sound tool design in a parrot.

The rarity of tool manufacture in wild parrots is surprising because they share key life-history traits with advanced tool-using species, including large brains, complex sociality and prolonged parental care. When it does occur, tool manufacture in parrots tends to be innovative, spontaneous and individually variable, but most cases have been in captivity. In the wild, only palm cockatoos (Probosciger aterrimus) have been observed using tools regularly. However, they are unusual because they use tools to enhance their displays rather than for foraging or self-maintenance. Males in northern Australia make two types of tool from sticks and seed pods, which they tap rhythmically against a tree during display. We analysed 256 sound tools retrieved from 70 display trees. Drumsticks (89% of tools) were used more often than seed pod tools; most males manufactured only drumsticks, but some made both types. Individual males differed significantly in the design of their drumsticks including the length, width and mass but we found no evidence that neighbours copied each other. We discuss the highly individualized preferences for sound tool design in context of the behavioural predispositions behind the rarity of tool manufacture in wild parrots.

A novel predictive algorithm to personalize autologous T-cell harvest for chimeric antigen receptor T-cell manufacture.

BACKGROUND AIMS: The most widely accepted starting materials for chimeric antigen receptor T-cell manufacture are autologous CD3+ T cells obtained via the process of leukapheresis, also known as T-cell harvest. As this treatment modality gains momentum and apheresis units struggle to meet demand for harvest slots, strategies to streamline this critical step are warranted. METHODS: This retrospective review of 262 T-cell harvests, with a control cohort of healthy donors, analyzed the parameters impacting CD3+ T-cell yield in adults with B-cell malignancies. The overall aim was to design a novel predictive algorithm to guide the required processed blood volume (PBV) (L) on the apheresis machine to achieve a specific CD3+ target yield. RESULTS: Factors associated with CD3+ T-cell yield on multivariate analysis included peripheral blood CD3+ count (natural log, ×109/L), hematocrit (HCT) and PBV with coefficients of 0.86 (95% confidence interval [CI], 0.80-0.92, P < 0.001), 1.30 (95% CI, 0.51-2.08, P = 0.001) and 0.09 (95% CI, 0.07-0.11, P < 0.001), respectively. The authors' model, incorporating CD3+ cell count, HCT and PBV (L), with an adjusted R2 of 0.87 and root-mean-square error of 0.26 in the training dataset, was highly predictive of CD3+ cell yield in the testing dataset. An online application to estimate PBV using this algorithm can be accessed at https://cd3yield.shinyapps.io/cd3yield/. CONCLUSIONS: The authors propose a transferrable model that incorporates clinical and laboratory variables accessible pre-harvest for use across the field of T-cell therapy. Pending further validation, such a model may be used to generate an individual leukapheresis plan and streamline the process of cell harvest, a well-recognized bottleneck in the industry.

A comprehensive review of quantum bioreactor cell manufacture: Research and clinical applications.

The Quantum cell expansion system manufactured by Terumo-BCT is perhaps the most widely reported Good Manufacturing Practice-compliant bioreactor used for the expansion of adherent cell populations, both for research purposes and clinical cell-based therapies/trials. Although the system was originally designed for adherent cell expansion, more recently suspension cultures and extracellular vesicle manufacturing protocols have been published using the Quantum system. Cell therapy research and regenerative medicine in general is a rapidly expanding field and as such it is likely that the use of this system will become even more widespread and perhaps mandatory, for both research and development and in the clinic. The purpose of this review is to describe, compare and discuss the diverse range of research and clinical applications currently using the Quantum system, which to our knowledge has not previously been reviewed. In addition, current and future challenges will also be discussed.

Engineered tumor-specific T cells using immunostimulatory photothermal nanoparticles.

BACKGROUND: Adoptive T cell therapy (ATCT) has been successful in treating hematological malignancies and is currently under investigation for solid-tumor therapy. In contrast to existing chimeric antigen receptor (CAR) T cell and/or antigen-specific T cell approaches, which require known targets, and responsive to the need for targeting a broad repertoire of antigens in solid tumors, we describe the first use of immunostimulatory photothermal nanoparticles to generate tumor-specific T cells. METHODS: Specifically, we subject whole tumor cells to Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) before culturing with dendritic cells (DCs), and subsequent stimulation of T cells. This strategy differs from previous approaches using tumor cell lysates because we use nanoparticles to mediate thermal and immunogenic cell death in tumor cells, rendering them enhanced antigen sources. RESULTS: In proof-of-concept studies using two glioblastoma (GBM) tumor cell lines, we first demonstrated that when PBNP-PTT was administered at a "thermal dose" targeted to induce the immunogenicity of U87 GBM cells, we effectively expanded U87-specific T cells. Further, we found that DCs cultured ex vivo with PBNP-PTT-treated U87 cells enabled 9- to 30-fold expansion of CD4+ and CD8+ T cells. Upon co-culture with target U87 cells, these T cells secreted interferon-É£ in a tumor-specific and dose-dependent manner (up to 647-fold over controls). Furthermore, T cells manufactured using PBNP-PTT ex vivo expansion elicited specific cytolytic activity against target U87 cells (donor-dependent 32-93% killing at an effector to target cell (E:T) ratio of 20:1) while sparing normal human astrocytes and peripheral blood mononuclear cells from the same donors. In contrast, T cells generated using U87 cell lysates expanded only 6- to 24-fold and killed 2- to 3-fold less U87 target cells at matched E:T ratios compared with T cell products expanded using the PBNP-PTT approach. These results were reproducible even when a different GBM cell line (SNB19) was used, wherein the PBNP-PTT-mediated approach resulted in a 7- to 39-fold expansion of T cells, which elicited 25-66% killing of the SNB19 cells at an E:T ratio of 20:1, depending on the donor. CONCLUSIONS: These findings provide proof-of-concept data supporting the use of PBNP-PTT to stimulate and expand tumor-specific T cells ex vivo for potential use as an adoptive T cell therapy approach for the treatment of patients with solid tumors.

Manufacture and evaluation of a HER2-positive breast cancer immunotoxin 4D5Fv-PE25.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) positive breast cancer is an aggressive subtype, accounting for around 20% of all breast cancers. The development of HER2-targeted therapy has substantially improved patient outcomes. Nevertheless, the increasing rate of side effects and resistance to targeted drugs limit their efficacy in clinical practice. In this study, we designed and synthesized a new immunotoxin, 4D5Fv-PE25, which targets HER2-positive breast cancer, and evaluated its effectiveness in vitro and in vivo. RESULTS: The 4D5Fv-PE25 was expressed in high-density Escherichia coli (E. coli.) using the fermentor method and refined via hydrophobicity, ion exchange, and filtration chromatography, achieving a 56.06% recovery rate. Additionally, the semi-manufactured product with 96% purity was prepared into freeze-dried powder by the lyophilized process. Flow cytometry was used to detect the expression of HER2 in SK-BR-3, BT-474, MDA-MB-231, and MDA-MB-468 breast cancer cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method was used for cytotoxicity assay, and the half-maximal inhibitory concentration (IC50) of 4D5Fv-PE25 lyophilized products to HER2-positive cell line SK-BR-3 was 12.53 ng/mL. The 4D5Fv-PE25 was injected into xenograft tumor mice via the tail vein on the 1st, 4th, and 8th day, it indicated that the growth of tumor volume was effectively inhibited for 24 days, although the 4D5Fv-PE25 was metabolized within 60 min by measuring the release of 3 H-Thymidine radiation. CONCLUSION: we succeeded in producing the 4D5Fv-PE25 freeze-dried powder using the prokaryotic expression method, and it could be employed as a potential drug for treating HER2-positive breast cancer.

Electrochemical sensor based on 3D-printed substrate by masked stereolithography (MSLA): a new, cheap, robust and sustainable approach for simple production of analytical platforms.

The development of miniaturized, sustainable and eco-friendly analytical sensors with low production cost is a current trend worldwide. Within this idea, this work presents  the innovative use of masked stereolithography (MSLA) 3D-printed substrates for the easy fabrication of pencil-drawn electrochemical sensors (MSLA-3D-PDE). The use of a non-toxic material such as pencil (electrodes) together with a biodegradable 3D printing resin (substrate) allowed the production of devices that are quite cheap (ca. US$ 0.11 per sensor) and with low environmental impact. Compared to paper, which is the most used substrate for manufacturing pencil-drawn electrodes, the MSLA-3D-printed substrate has the advantages of not absorbing water (hydrophobicity) or becoming crinkled and weakened when in contact with solutions. These features provide more reproducible, reliable, stable, and long-lasting sensors. The MSLA-3D-PDE, in conjunction with the custom cell developed, showed excellent robustness and electrochemical performance similar to that observed of the glassy carbon electrode, without the need of any activation procedure. The analytical applicability of this platform was explored through the quantification of omeprazole in pharmaceuticals. A limit of detection (LOD) of 0.72 µmol L-1 was achieved, with a linear range of 10 to 200 µmol L-1. Analysis of real samples provided results that were highly concordant with those obtained by UV-Vis spectrophotometry (relative error ≤ 1.50%). In addition, the greenness of this approach was evaluated and confirmed by a quantitative methodology (Eco-Scale index). Thus, the MSLA-3D-PDE appears as a new and sustainable tool with great potential of use in analytical electrochemistry.

Image-Based Detection of Modifications in Assembled PCBs with Deep Convolutional Autoencoders.

In this paper, we introduce a one-class learning approach for detecting modifications in assembled printed circuit boards (PCBs) based on photographs taken without tight control over perspective and illumination conditions. Anomaly detection and segmentation are essential for several applications, where collecting anomalous samples for supervised training is infeasible. Given the uncontrolled environment and the huge number of possible modifications, we address the problem as a case of anomaly detection, proposing an approach that is directed towards the characteristics of that scenario, while being well suited for other similar applications. We propose a loss function that can be used to train a deep convolutional autoencoder based only on images of the unmodified board-which allows overcoming the challenge of producing a representative set of samples containing anomalies for supervised learning. We also propose a function that explores higher-level features for comparing the input image and the reconstruction produced by the autoencoder, allowing the segmentation of structures and components that differ between them. Experiments performed on a dataset built to represent real-world situations (which we made publicly available) show that our approach outperforms other state-of-the-art approaches for anomaly segmentation in the considered scenario, while producing comparable results on a more general object anomaly detection task.