Time-of-Flight MRA of Intracranial Aneurysms with Interval Surveillance, Clinical Segmentation and Annotations.

Intracranial aneurysms (IAs) are present in 2-6% of the global population and can be catastrophic upon rupture with a mortality rate of 30-50%. IAs are commonly detected through time-of-flight magnetic resonance angiography (TOF-MRA), however, this data is rarely available for research and training purposes. The provision of imaging resources such as TOF-MRA images is imperative to develop new strategies for IA detection, rupture prediction, and surgical training. To support efforts in addressing data availability bottlenecks, we provide an open-access TOF-MRA dataset comprising 63 patients, of which 24 underwent interval surveillance imaging by TOF-MRA. Patient scans were evaluated by a neuroradiologist, providing aneurysm and vessel segmentations, clinical annotations, 3D models, in addition to 3D Slicer software environments containing all this data for each patient. This dataset is the first to provide interval surveillance imaging for supporting the understanding of IA growth and stability. This dataset will support computational and experimental research into IA dynamics and assist surgical and radiology training in IA treatment.

Melt Electrowriting of Nylon-12 Microfibers with an Open-Source 3D Printer.

This study demonstrates how either a heated flat or cylindrical collector enables defect-free melt electrowriting (MEW) of complex geometries from high melting temperature polymers. The open-source "MEWron" printer uses nylon-12 filament and combined with a heated flat or cylindrical collector, produces well-defined fibers with diameters ranging from 33 ± 4 to 95 ± 3 µm. Processing parameters for stable jet formation and minimal defects based on COMSOL thermal modeling for hardware design are optimized. The balance of processing temperature and collector temperature is achieved to achieve auxetic patterns, while showing that annealing nylon-12 tubes significantly alters their mechanical properties. The samples exhibit varied pore sizes and wall thicknesses influenced by jet dynamics and fiber bridging. Tensile testing shows nylon-12 tubes are notably stronger than poly(ε-caprolactone) ones and while annealing has limited impact on tensile strength, yield, and elastic modulus, it dramatically reduces elongation. The equipment described and material used broadens MEW applications for high melting point polymers and highlights the importance of cooling dynamics for reproducible samples.

An automated parametric ear model to improve frugal 3D scanning methods for the advanced manufacturing of high-quality prosthetic ears.

Ear prostheses are commonly used for restoring aesthetics to those suffering missing or malformed external ears. Traditional fabrication of these prostheses is labour intensive and requires expert skill from a prosthetist. Advanced manufacturing including 3D scanning, modelling and 3D printing has the potential to improve this process, although more work is required before it is ready for routine clinical use. In this paper, we introduce a parametric modelling technique capable of producing high quality 3D models of the human ear from low-fidelity, frugal, patient scans; significantly reducing time, complexity and cost. Our ear model can be tuned to fit the frugal low-fidelity 3D scan through; (a) manual tuning, or (b) our automated particle filter approach. This potentially enables low-cost smartphone photogrammetry-based 3D scanning for high quality personalised 3D printed ear prosthesis. In comparison to standard photogrammetry, our parametric model improves completeness, from (81 ± 5)% to (87 ± 4)%, with only a modest reduction in accuracy, with root mean square error (RMSE) increasing from (1.0 ± 0.2) mm to (1.5 ± 0.2) mm (relative to metrology rated reference 3D scans, n = 14). Despite this reduction in the RMS accuracy, our parametric model improves the overall quality, realism, and smoothness. Our automated particle filter method differs only modestly compared to manual adjustments. Overall, our parametric ear model can significantly improve quality, smoothness and completeness of 3D models produced from 30-photograph photogrammetry. This enables frugal high-quality 3D ear models to be produced for use in the advanced manufacturing of ear prostheses.

Personalized Offloading Treatments for Healing Plantar Diabetic Foot Ulcers.

BACKGROUND: Non-removable knee-high devices are the gold-standard offloading treatments to heal plantar diabetic foot ulcers (DFUs). These devices are underused in practice for a variety of reasons. Recommending these devices for all patients, regardless of their circumstances and preferences influencing their ability to tolerate the devices, does not seem a fruitful approach. PURPOSE: The aim of this article is to explore the potential implications of a more personalized approach to offloading DFUs and suggest avenues for future research and development. METHODS: Non-removable knee-high devices effectively heal plantar DFUs by reducing plantar pressure and shear at the DFU, reducing weight-bearing activity and enforcing high adherence. We propose that future offloading devices should be developed that aim to optimize these mechanisms according to each individual's needs. We suggest three different approaches may be developed to achieve such personalized offloading treatment. First, we suggest modular devices, where different mechanical features (rocker-bottom sole, knee-high cast walls/struts, etc.) can be added or removed from the device to accommodate different patients' needs and the evolving needs of the patient throughout the treatment period. Second, advanced manufacturing techniques and novel materials could be used to personalize the design of their devices, thereby improving common hindrances to their use, such as devices being heavy, bulky, and hot. Third, sensors could be used to provide real-time feedback to patients and clinicians on plantar pressures, shear, weight-bearing activity, and adherence. CONCLUSIONS: By the use of these approaches, we could provide patients with personalized devices to optimize plantar tissue stress, thereby improving clinical outcomes.

Laser Sintering Approaches for Bone Tissue Engineering.

The adoption of additive manufacturing (AM) techniques into the medical space has revolutionised tissue engineering. Depending upon the tissue type, specific AM approaches are capable of closely matching the physical and biological tissue attributes, to guide tissue regeneration. For hard tissue such as bone, powder bed fusion (PBF) techniques have significant potential, as they are capable of fabricating materials that can match the mechanical requirements necessary to maintain bone functionality and support regeneration. This review focuses on the PBF techniques that utilize laser sintering for creating scaffolds for bone tissue engineering (BTE) applications. Optimal scaffold requirements are explained, ranging from material biocompatibility and bioactivity, to generating specific architectures to recapitulate the porosity, interconnectivity, and mechanical properties of native human bone. The main objective of the review is to outline the most common materials processed using PBF in the context of BTE; initially outlining the most common polymers, including polyamide, polycaprolactone, polyethylene, and polyetheretherketone. Subsequent sections investigate the use of metals and ceramics in similar systems for BTE applications. The last section explores how composite materials can be used. Within each material section, the benefits and shortcomings are outlined, including their mechanical and biological performance, as well as associated printing parameters. The framework provided can be applied to the development of new, novel materials or laser-based approaches to ultimately generate bone tissue analogues or for guiding bone regeneration.

3D Plotting of Calcium Phosphate Cement and Melt Electrowriting of Polycaprolactone Microfibers in One Scaffold: A Hybrid Additive Manufacturing Process.

The fabrication of patient-specific scaffolds for bone substitutes is possible through extrusion-based 3D printing of calcium phosphate cements (CPC) which allows the generation of structures with a high degree of customization and interconnected porosity. Given the brittleness of this clinically approved material, the stability of open-porous scaffolds cannot always be secured. Herein, a multi-technological approach allowed the simultaneous combination of CPC printing with melt electrowriting (MEW) of polycaprolactone (PCL) microfibers in an alternating, tunable design in one automated fabrication process. The hybrid CPC+PCL scaffolds with varying CPC strand distance (800-2000 µm) and integrated PCL fibers featured a strong CPC to PCL interface. While no adverse effect on mechanical stiffness was detected by the PCL-supported scaffold design; the microfiber integration led to an improved integrity. The pore distance between CPC strands was gradually increased to identify at which critical CPC porosity the microfibers would have a significant impact on pore bridging behavior and growth of seeded cells. At a CPC strand distance of 1600 µm, after 2 weeks of cultivation, the incorporation of PCL fibers led to pore coverage by a human mesenchymal stem cell line and an elevated proliferation level of murine pre-osteoblasts. The integrated fabrication approach allows versatile design adjustments on different levels.

Personalized Volumetric Tissue Generation by Enhancing Multiscale Mass Transport through 3D Printed Scaffolds in Perfused Bioreactors.

Engineered tissues provide an alternative to graft material, circumventing the use of donor tissue such as autografts or allografts and non-physiological synthetic implants. However, their lack of vasculature limits the growth of volumetric tissue more than several millimeters thick which limits their success post-implantation. Perfused bioreactors enhance nutrient mass transport inside lab-grown tissue but remain poorly customizable to support the culture of personalized implants. Here, a multiscale framework of computational fluid dynamics (CFD), additive manufacturing, and a perfusion bioreactor system are presented to engineer personalized volumetric tissue in the laboratory. First, microscale 3D printed scaffold pore geometries are designed and 3D printed to characterize media perfusion through CFD and experimental fluid testing rigs. Then, perfusion bioreactors are custom-designed to combine 3D printed scaffolds with flow-focusing inserts in patient-specific shapes as simulated using macroscale CFD. Finally, these computationally optimized bioreactor-scaffold assemblies are additively manufactured and cultured with pre-osteoblast cells for 7, 20, and 24 days to achieve tissue growth in the shape of human calcaneus bones of 13 mL volume and 1 cm thickness. This framework enables an intelligent model-based design of 3D printed scaffolds and perfusion bioreactors which enhances nutrient transport for long-term volumetric tissue growth in personalized implant shapes. The novel methods described here are readily applicable for use with different cell types, biomaterials, and scaffold microstructures to research therapeutic solutions for a wide range of tissues.

In vitro and in vivo investigation of a zonal microstructured scaffold for osteochondral defect repair.

Articular cartilage is comprised of zones that vary in architecture, extracellular matrix composition, and mechanical properties. Here, we designed and engineered a porous zonal microstructured scaffold from a single biocompatible polymer (poly [ϵ-caprolactone]) using multiple fabrication strategies: electrospinning, spherical porogen leaching, directional freezing, and melt electrowriting. With this approach we mimicked the zonal structure of articular cartilage and produced a stiffness gradient through the scaffold which aligns with the mechanics of the native tissue. Chondrocyte-seeded scaffolds accumulated extracellular matrix including glycosaminoglycans and collagen II over four weeks in vitro. This prompted us to further study the repair efficacy in a skeletally mature porcine model. Two osteochondral lesions were produced in the trochlear groove of 12 animals and repaired using four treatment conditions: (1) microstructured scaffold, (2) chondrocyte seeded microstructured scaffold, (3) MaioRegen™, and (4) empty defect. After 6 months the defect sites were harvested and analyzed using histology, micro computed tomography, and Raman microspectroscopy mapping. Overall, the scaffolds were retained in the defect space, repair quality was repeatable, and there was clear evidence of osteointegration. The repair quality of the microstructured scaffolds was not superior to the control based on histological scoring; however, the lower score was biased by the lack of histological staining due to the limited degradation of the implant at 6 months. Longer follow up studies (e.g., 1 yr) will be required to fully evaluate the efficacy of the microstructured scaffold. In conclusion, we found consistent scaffold retention, osteointegration, and prolonged degradation of the microstructured scaffold, which we propose may have beneficial effects for the long-term repair of osteochondral defects.

Image analyses for engineering advanced tissue biomanufacturing processes.

Industrial cell culture processes are inherently expensive, time-consuming, and variable. These limitations have become a critical bottleneck for the industrial translation of human cell and tissue biomanufacturing, as few human cell culture products deliver sufficient benefit, value, and consistency to offset their high manufacturing costs and produce useful clinical or biomedical solutions. Recent advances in biomedical image analysis and computational modelling can enhance the design and operation of high-efficiency tissue biomanufacturing platforms, as well as the high-content characterisation and monitoring of culture performance, to enable bioprocess control, optimisation, and automation. These computational technologies aim to maximize culture outcomes while minimizing variability and process development expense. In this review, we outline current resources and approaches which harness biomedical imaging and image-based computational models to design and operate efficient and robust human tissue biomanufacturing platforms.

Soft pneumatic actuators for mimicking multi-axial femoropopliteal artery mechanobiology.

Tissue biomanufacturing aims to produce lab-grown stem cell grafts and biomimetic drug testing platforms but remains limited in its ability to recapitulate native tissue mechanics. The emerging field of soft robotics aims to emulate dynamic physiological locomotion, representing an ideal approach to recapitulate physiologically complex mechanical stimuli and enhance patient-specific tissue maturation. The kneecap's femoropopliteal artery (FPA) represents a highly flexible tissue across multiple axes during blood flow, walking, standing, and crouching positions, and these complex biomechanics are implicated in the FPA's frequent presentation of peripheral artery disease. We developed a soft pneumatically actuated (SPA) cell culture platform to investigate how patient-specific FPA mechanics affect lab-grown arterial tissues. Silicone hyperelastomers were screened for flexibility and biocompatibility, then additively manufactured into SPAs using a simulation-based design workflow to mimic normal and diseased FPA extensions in radial, angular, and longitudinal dimensions. SPA culture platforms were seeded with mesenchymal stem cells, connected to a pneumatic controller, and provided with 24 h multi-axial exercise schedules to demonstrate the effect of dynamic conditioning on cell alignment, collagen production, and muscle differentiation without additional growth factors. Soft robotic bioreactors are promising platforms for recapitulating patient-, disease-, and lifestyle-specific mechanobiology for understanding disease, treatment simulations, and lab-grown tissue grafts.

Development of 3D Printed Biodegradable Mesh with Antimicrobial Properties for Pelvic Organ Prolapse.

To address the increasing demand for safe and effective treatment options for pelvic organ prolapse (POP) due to the worldwide ban of the traditional polypropylene meshes, this study introduced degradable polycaprolactone (PCL)/polyethylene glycol (PEG) composite meshes fabricated with melt-electrowriting (MEW). Two PCL/PEG mesh groups: 90:10 and 75:25 (PCL:PEG, wt%) were fabricated and characterized for their degradation rate and mechanical properties, with PCL meshes used as a control. The PCL/PEG composites showed controllable degradation rates by adjusting the PEG content and produced mechanical properties, such as maximal forces, that were higher than PCL alone. The antibacterial properties of the meshes were elicited by coating them with a commonly used antibiotic: azithromycin. Two dosage levels were used for the coating: 0.5 mg and 1 mg per mesh, and both dosage levels were found to be effective in suppressing the growth of S. aureus bacteria. The biocompatibility of the meshes was assessed using human immortalized adipose derived mesenchymal stem cells (hMSC). In vitro assays were used to assess the cell viability (LIVE/DEAD assay), cell metabolic activity (alamarBlue assay) and cell morphology on the meshes (fluorescent and electron microscopy). The cell attachment was found to decrease with increased PEG content. The freshly drug-coated meshes showed signs of cytotoxicity during the cell study process. However, when pre-released for 14 days in phosphate buffered saline, the initial delay in cell attachment on the drug-coated mesh groups showed full recovery at the 14-day cell culture time point. These results indicated that the PCL/PEG meshes with antibiotics coating will be an effective anti-infectious device when first implanted into the patients, and, after about 2 weeks of drug release, the mesh will be supporting cell attachment and proliferation. These meshes demonstrated a potential effective treatment option for POP that may circumvent the issues related to the traditional polypropylene meshes.

Ultrasound Imaging Offers Promising Alternative to Create 3-D Models for Personalised Auricular Implants.

Three-dimensional imaging and advanced manufacturing are being applied in health care research to create novel diagnostic and surgical planning methods, as well as personalised treatments and implants. For ear reconstruction, where a cartilage-shaped implant is embedded underneath the skin to re-create shape and form, volumetric imaging and segmentation processing to capture patient anatomy are particularly challenging. Here, we introduce 3-D ultrasound (US) as an available option for imaging the external ear and underlying auricular cartilage structure, and compare it with computed tomography (CT) and magnetic resonance imaging (MRI) against micro-CT (µCT) as a high-resolution reference (gold standard). US images were segmented to create 3-D models of the auricular cartilage and compared against models generated from µCT to assess accuracy. We found that CT was significantly less accurate than the other methods (root mean square [RMS]: 1.30 ± 0.5 mm) and had the least contrast between tissues. There was no significant difference between MRI (RMS: 0.69 ± 0.2 mm) and US (0.55 ± 0.1 mm). US was also the least expensive imaging method at half the cost of MRI. These results unveil a novel use of ultrasound imaging that has not been presented before, as well as support its more widespread use in biofabrication as a low-cost imaging technique to create patient-specific 3D models and implants.

Capturing patient anatomy for designing and manufacturing personalized prostheses.

Prostheses play a critical role in healthcare provision for many patients and encompass aesthetic facial prostheses, prosthetic limbs and prosthetic joints, bones, and other implantable medical devices in musculoskeletal surgery. An increasingly important component in cutting-edge healthcare treatments is the ability to accurately capture patient anatomy in order to guide the manufacture of personalized prostheses. This article examines methods for capturing patient anatomy and discusses the degrees of personalization in medical manufacturing alongside a summary of current trends in scanning technology with a focus on identifying workflows for incorporating personalization into patient-specific products. Over the next decade, with increased harmonization of both personalization and automated prosthetic manufacturing will be the realization of improved patient compliance, satisfaction, and clinical outcomes.

Melt electro-written scaffolds with box-architecture support orthogonally oriented collagen.

Melt electro-writing (MEW) is a state-of-the-art technique that supports fabrication of 3D, precisely controlled and reproducible fiber structures. A standard MEW scaffold design is a box-structure, where a repeat layer of 90° boxes is produced from a single fiber. In 3D form (i.e. multiple layers), this structure has the potential to mimic orthogonal arrangements of collagen, as observed in the corneal stroma. In this study, we determined the response of human primary corneal stromal cells and their deposited fibrillar collagen (detected using a CNA35 probe) following six weeksin vitroculture on these box-structures made from poly(ϵ-caprolactone) (PCL). Comparison was also made to glass substrates (topography-free) and electrospun PCL fibers (aligned topography). Cell orientation and collagen deposition were non-uniform on glass substrates. Electrospun scaffolds supported an excellent parallel arrangement of cells and deposited collagen to the underlying architecture of aligned fibers, but there was no evidence of bidirectional collagen. In contrast, MEW scaffolds encouraged the formation of a dense, interconnected cellular network and deposited fibrillar collagen layers with a distinct orthogonal-arrangement. Collagen fibrils were particularly dominant through the middle layers of the MEW scaffolds' total thickness and closer examination revealed these fibrils to be concentrated within the pores' central regions. With the demand for donor corneas far exceeding the supply-leaving many with visual impairment-the application of MEW as a potential technique to recreate the corneal stroma with spontaneous, bidirectional collagen organization warrants further study.

Poly-ε-Caprolactone/Fibrin-Alginate Scaffold: A New Pro-Angiogenic Composite Biomaterial for the Treatment of Bone Defects.

We hypothesized that a composite of 3D porous melt-electrowritten poly-ɛ-caprolactone (PCL) coated throughout with a porous and slowly biodegradable fibrin/alginate (FA) matrix would accelerate bone repair due to its angiogenic potential. Scanning electron microscopy showed that the open pore structure of the FA matrix was maintained in the PCL/FA composites. Fourier transform infrared spectroscopy and differential scanning calorimetry showed complete coverage of the PCL fibres by FA, and the PCL/FA crystallinity was decreased compared with PCL. In vitro cell work with osteoprogenitor cells showed that they preferentially bound to the FA component and proliferated on all scaffolds over 28 days. A chorioallantoic membrane assay showed more blood vessel infiltration into FA and PCL/FA compared with PCL, and a significantly higher number of bifurcation points for PCL/FA compared with both FA and PCL. Implantation into a rat cranial defect model followed by microcomputed tomography, histology, and immunohistochemistry after 4- and 12-weeks post operation showed fast early bone formation at week 4, with significantly higher bone formation for FA and PCL/FA compared with PCL. However, this phenomenon was not extrapolated to week 12. Therefore, for long-term bone regeneration, tuning of FA degradation to ensure syncing with new bone formation is likely necessary.

Degradation of Melt Electrowritten PCL Scaffolds Following Melt Processing and Plasma Surface Treatment.

Melt electrowriting (MEW) has been widely used to process polycaprolactone (PCL) into highly ordered microfiber scaffolds with controllable architecture and geometry. However, the integrity of PCL during specific processes involved in routine MEW scaffold development has not yet been thoroughly investigated. This study investigates the impact of MEW processing on PCL following exposure to high temperatures required for melt extrusion as well as atmospheric plasma, a widely used surface treatment for improving MEW scaffold hydrophilicity. The change in polymer molecular weight and melt temperature is characterized, in comparing unprocessed and processed samples, in addition to analysis of the mechanical and surface properties of the scaffolds. No significant difference in the molecular weight or mechanical properties of the PCL scaffolds is evident following 5 days of cyclic heating to 90 °C. Exposure to plasma for up to 5 min significantly increased hydrophilicity and surface adhesion force, characterized via contact angle and atomic force microscope, however, significant polymer degradation occurred evidenced by increased brittleness of the scaffolds. This study demonstrates the degradation of PCL following fabrication via MEW and surface treatment to guide the optimization of scaffold development for subsequent applications in tissue engineering and biofabrication.

A quantitative analysis of cell bridging kinetics on a scaffold using computer vision algorithms.

Tissue engineering involves the seeding of cells into a structural scaffolding to regenerate the architecture of damaged or diseased tissue. To effectively design a scaffold, an understanding of how cells collectively sense and react to the geometry of their local environment is needed. Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro scaffold model to study cellular spatial-temporal kinetics. These scaffolds were paired with custom computer vision algorithms to investigate cell nuclei, cell membrane actin and scaffold fibres over different pore sizes (200-600 µm) and time points (28 days). We find that cells proliferated much faster in the smaller (200 µm) pores which halved the time until confluence versus larger (500 and 600 µm) pores. Our analysis of stained actin fibres revealed that cells were highly aligned to the fibres and the leading edge of the pore filling front, and we found that cells behind the leading edge were not aligned in any particular direction. This study provides a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model to inform the design of more effective synthetic tissue engineering scaffolds for tissue regeneration. STATEMENT OF SIGNIFICANCE: Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro model to study cellular spatial-temporal kinetics to provide a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model. The insights presented in this work help to inform the design of more effective synthetic tissue engineering scaffolds by reducing cell culture time; which is valuable information for the implant or lab-grown-meat industries.

Scaffold-guided bone regeneration in large volume tibial segmental defects.

Large volume losses in weight bearing long bones are a major challenge in clinical practice. Despite multiple innovations over the last decades, significant limitations subsist in current clinical treatment options which is driving a strong clinical demand for clinically translatable treatment alternatives, including bone tissue engineering applications. Despite these shortcomings, preclinical large animal models of large volume segmental bone defects to investigate the regenerative capacity of bone tissue engineering strategies under clinically relevant conditions are rarely described in literature. We herein present a newly established preclinical ovine animal model for the treatment of XL volume (19 cm3) segmental tibial defects. In eight aged male Merino sheep (age > 6 years) a mid-diaphyseal tibial segmental defect was created and stabilized with a 5.6 mm Dynamic Compression Plate (DCP). We present short-term (3 months) and long-term (12-15 months) results of a pilot study using medical grade Polycaprolactone-Tricalciumphosphate (mPCL-TCP) scaffolds combined with a dose of 2 mg rhBMP-7 delivered in Platelet-Rich- Plasma (PRP). Furthermore, detailed analyses of the mechanical properties of the scaffolds as well as interfragmentary movement (IFM) and DCP-surface strain in vitro and a comprehensive description of the surgical and post-surgery protocol and post-mortem analysis is given.

Novel resin tissue array system reduces sample preparation time, labour and reagent costs in bone tissue histology.

Resin histology plays an essential role in the analysis of hard tissues, such as bone and teeth, as well as in the context of metallic implant analysis. However, the techniques of resin embedding, followed by ground sectioning, are very costly due to significantly increased reagent cost and labour time when compared to the conventional paraffin histology approach. In the present study, a novel resin array system was developed to increase the affordability of a project analysing rat femur tissues containing metallic or polymeric implants. The resin array system enabled the simultaneous embedding of the femur samples in groups of eight samples compared to the conventional resin method where samples are processed individually. The ground sections produced with the resin array system allowed uniform ROI selection, ground section thickness, staining consistency, and histological analysis with Goldner's trichrome stain, offering a substantial opportunity for reproducible immunohistochemistry which is unable to be achieved when processing samples embedded individually. The application of this novel resin array system significantly reduced resource usage when compared to doing the same analysis on individual samples. A reduction of approximately 40% was achieved for both total labour time and total reagent cost through the use of the array system compared with individual embedding. This novel resin array system has widespread applicability to many bone, hard tissue, and metallic implant studies, offering substantial conservation of research funds and increased accessibility to advanced techniques for commercial partners due to more cost-effective sample preparation and more accurate, reproducible data.