Laboratory Automation

实验室自动化
  • 文章类型: Journal Article
    有越来越多的人,欢迎,开放的硬件趋势,科学团队建立和分享他们的新仪器的设计。这些设备,通常建立在低成本的微处理器和微控制器上,可以很容易地连接以实现复杂的,自动化和智能实验。当设计使用开放通信网络标准时,来自不同实验室和制造商的设备可以使用单一协议进行控制,甚至可以相互通信。然而,科学实验室仍然有大多数旧的,功能完美的设备,往往使用旧的,有时是专有的,通信标准。为了鼓励在现代自动化实验中继续和综合使用该设备,我们开发和演示LabThingsRetro。这使我们能够改造旧仪器以使用现代物联网标准,我们用光学显微镜的闭环反馈来演示,数字成像和流体泵送。
    There has been an increasing, and welcome, open hardware trend towards science teams building and sharing their designs for new instruments. These devices, often built upon low-cost microprocessors and microcontrollers, can be readily connected to enable complex, automated and smart experiments. When designed to use open communication web standards, devices from different laboratories and manufacturers can be controlled using a single protocol and even communicate with each other. However, science labs still have a majority of old, perfectly functional equipment which tends to use older, and sometimes proprietary, standards for communications. In order to encourage the continued and integrated use of this equipment in modern automated experiments, we develop and demonstrate LabThings Retro. This allows us to retrofit old instruments to use modern Web-of-Things standards, which we demonstrate with closed-loop feedback involving an optical microscope, digital imaging and fluid pumping.
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  • 文章类型: Journal Article
    支持性的机器人解决方案接管了平凡的生活,而是生物医学研究和开发实验室人力的基本任务。协作和移动机器人技术的最新技术可以在以人为中心和低结构的环境中使用。他们的适应能力,然而,受到它们引入的额外复杂性的阻碍。在我们的论文中,我们旨在纠缠复杂的实验室机器人集成架构。我们从分层分解实验室工作流程开始,并将活动表示映射到自动化控制架构的层和组件。我们详细阐述了这个框架,以拾取和放置实验室器皿运输为例,这是一个至关重要的支持步骤,我们认为这是该领域专家最感兴趣的领域。我们的概念提案用作参考架构模型,其关键原则在参考实现中使用,并符合国际标准化工作。
    Supportive robotic solutions take over mundane, but essential tasks from human workforce in biomedical research and development laboratories. The newest technologies in collaborative and mobile robotics enable the utilization in the human-centered and low-structured environment. Their adaptability, however, is hindered by the additional complexity that they introduce. In our paper we aim to entangle the convoluted laboratory robot integration architectures. We begin by hierarchically decomposing the laboratory workflows, and mapping the activity representations to layers and components of the automation control architecture. We elaborate the framework in detail on the example of pick-and-place labware transportation - a crucial supportive step, which we identified as the number one area of interest among experts of the field. Our concept proposal serves as a reference architecture model, the key principles of which were used in reference implementations, and are in line with international standardization efforts.
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  • 文章类型: Editorial
    背景:现代高通量技术能够同时处理大量样品,同时还提供快速和准确的程序。近年来,自动液体处理工作站已经成为可重复样品制备的既定技术。他们提供了灵活性,使它们适用于不断扩大的应用范围。通常,这样的方法对于主要设计用于细胞系处理和异源生物测试的实验程序是完善的。相反,很少关注自动化液体处理器在整个生物体分析中的应用,这通常涉及耗时的实验室程序。
    结果:这里,Annona等人提出了所有步骤的全自动工作流程,从RNA提取到实时PCR处理,用于海鞘海洋模型Cionarobusta中的基因表达定量。对于过程验证,作者比较了使用液体处理器获得的结果与经典手动程序的结果。结果显示了可比的结果,特别是在样品处理的初始步骤中,证明了显著的时间节省。
    结论:这项工作将该技术的可能应用领域扩展到全身生物,缓解手动程序可能产生的问题。通过最小化错误,避免交叉污染,减少动手时间,简化程序,它可以用于大规模筛查调查。
    BACKGROUND: Modern high-throughput technologies enable the processing of a large number of samples simultaneously, while also providing rapid and accurate procedures. In recent years, automated liquid handling workstations have emerged as an established technology for reproducible sample preparation. They offer flexibility, making them suitable for an expanding range of applications. Commonly, such approaches are well-developed for experimental procedures primarily designed for cell-line processing and xenobiotics testing. Conversely, little attention is focused on the application of automated liquid handlers in the analysis of whole organisms, which often involves time-consuming laboratory procedures.
    RESULTS: Here, Annona et al present a fully automated workflow for all steps, from RNA extraction to real-time PCR processing, for gene expression quantification in the ascidian marine model Ciona robusta. For procedure validation, the authors compared the results obtained with the liquid handler with those of the classical manual procedure. The outcome revealed comparable results, demonstrating a remarkable time saving particularly in the initial steps of sample processing.
    CONCLUSIONS: This work expands the possible application fields of this technology to whole-body organisms, mitigating issues that can arise from manual procedures. By minimizing errors, avoiding cross-contamination, decreasing hands-on time and streamlining the procedure, it could be employed for large-scale screening investigations.
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  • 文章类型: Journal Article
    全面实验室自动化(TLA)是微生物实验室的重要组成部分,越来越多的出版物表明自动化在分析标准化方面的潜在影响。条纹质量,和周转时间(TAT)。该项目的目的是对TLA对尿液等常用处理标本的工作流程的影响进行详细调查。这是一项回顾性观察研究,比较了两个时间段(TLA前与TLA后)的尿液样本培养处理。在TLA前阶段共接种了35,864个尿液样本,在TLA后阶段共接种了47,283个尿液样本。从划线到鉴定的中位时间从TLA前的22.3小时减少到TLA后的21.4小时(p<0.001),从划线到最终验证报告的中位时间从TLA前的24.3小时减少到TLA后的23小时(p<0.001)。进一步的分析表明,观察到的TAT差异主要是由污染样品和阳性样品驱动的。我们的发现表明,TLA有可能减少实验室样品的周转时间。然而,实验室工作流程的改变(例如延长平板读数和抗生素药敏试验的开放时间或减少孵育时间)可能会进一步最大化TLA的效率并优化TAT.
    Total laboratory automation (TLA) is a valuable component of microbiology laboratories and a growing number of publications suggest the potential impact of automation in terms of analysis standardization, streaking quality, and the turnaround time (TAT). The aim of this project was to perform a detailed investigation of the impact of TLA on the workflow of commonly treated specimens such as urine. This is a retrospective observational study comparing two time periods (pre TLA versus post TLA) for urine specimen culture processing. A total of 35,864 urine specimens were plated during the pre-TLA period and 47,283 were plated during the post-TLA period. The median time from streaking to identification decreased from 22.3 h pre TLA to 21.4 h post TLA (p < 0.001), and the median time from streaking to final validation of the report decreased from 24.3 h pre TLA to 23 h post TLA (p < 0.001). Further analysis revealed that the observed differences in TAT were mainly driven by the contaminated and positive samples. Our findings demonstrate that TLA has the potential to decrease turnaround times of samples in a laboratory. Nevertheless, changes in laboratory workflow (such as extended opening hours for plate reading and antibiotic susceptibility testing or decreased incubation times) might further maximize the efficiency of TLA and optimize TATs.
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  • 文章类型: Journal Article
    细胞热移位测定(CETSA)使得能够研究细胞环境中的蛋白质-配体相互作用。它提供了有关小分子和大分子配体在相关生理环境中的结合亲和力和特异性的有价值的信息,从而形成了药物发现的独特工具。尽管存在用于扩展CETSA的高通量实验室协议,随后的数据分析和质量控制仍然很费力,限制了实验通量。这里,我们引入了可扩展且稳健的数据分析工作流程,该流程允许将CETSA整合到常规高通量筛查(HT-CETSA)中.这个新的工作流程自动化数据分析,并纳入质量控制(QC),包括异常值检测,样品和板QC,和结果分类。我们描述了工作流程,并展示了它对典型实验工件的鲁棒性,显示缩放效果,并讨论了通过消除手动数据处理步骤来实现数据分析自动化的影响。
    The Cellular Thermal Shift Assay (CETSA) enables the study of protein-ligand interactions in a cellular context. It provides valuable information on the binding affinity and specificity of both small and large molecule ligands in a relevant physiological context, hence forming a unique tool in drug discovery. Though high-throughput lab protocols exist for scaling up CETSA, subsequent data analysis and quality control remain laborious and limit experimental throughput. Here, we introduce a scalable and robust data analysis workflow which allows integration of CETSA into routine high throughput screening (HT-CETSA). This new workflow automates data analysis and incorporates quality control (QC), including outlier detection, sample and plate QC, and result triage. We describe the workflow and show its robustness against typical experimental artifacts, show scaling effects, and discuss the impact of data analysis automation by eliminating manual data processing steps.
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  • 文章类型: Journal Article
    本文介绍了工程生物学策略和技术在实验室工作流程自动化中的应用,主要是在基于设计的生物材料和生物设计应用的背景下,Build,测试和学习范例。自动化程度越来越高的趋势也带来了一系列挑战。一方面,自动化与更高的吞吐量和更高的可复制性相关。另一方面,自动化工作流的实现需要的指令集远比手动工作流所需的要广泛得多。自动化任务还必须按照工作流中指定的顺序执行,用正确的逻辑,利用合适的生物铸造资源,同时收集测量和相关数据。本文介绍了一种自动化工作流程的方法,该方法正在SynbiCITE的伦敦生物铸造厂进行试验。该解决方案用有向图表示工作流程,使用编排器来执行它们,并依赖于现有的标准。该方法非常灵活,不仅适用于单个位置的工作流程自动化,还适用于分布式工作流程(例如,用于生物制造)。最后一部分介绍了实现的概述-使用基于稀释的测定的简单示例,测量,和数据分析工作流程。
    The paper addresses the application of engineering biology strategies and techniques to the automation of laboratory workflow-primarily in the context of biofoundries and biodesign applications based on the Design, Build, Test and Learn paradigm. The trend toward greater automation comes with its own set of challenges. On the one hand, automation is associated with higher throughput and higher replicability. On the other hand, the implementation of an automated workflow requires an instruction set that is far more extensive than that required for a manual workflow. Automated tasks must also be conducted in the order specified in the workflow, with the right logic, utilizing suitable biofoundry resources, and at scale-while simultaneously collecting measurements and associated data. The paper describes an approach to an automated workflow that is being trialed at the London Biofoundry at SynbiCITE. The solution represents workflows with directed graphs, uses orchestrators for their execution, and relies on existing standards. The approach is highly flexible and applies to not only workflow automation in single locations but also distributed workflows (e.g. for biomanufacturing). The final section presents an overview of the implementation-using the simple example of an assay based on a dilution, measurement, and data analysis workflow.
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  • 文章类型: Journal Article
    糖组学,关注聚糖在生物过程中的作用,特别是它们对折叠的影响,糖缀合物样抗体的稳定性和受体相互作用,对我们理解生物学至关重要。免疫球蛋白G(IgG)N-糖基化的变化与各种生理和病理生理条件有关。然而,耗时的手动样品制备是糖组学诊断实施中的限制之一。该研究旨在开发一种在TecanFreedomEvo200平台上进行样品制备的自动化方法,并将其效率和精度与手动方法进行比较。
    最初的方法开发包括32个混合血浆技术重复。在方法比较中使用另外24个汇集的样品以及从10,001Dalmatians生物库收集的78个随机重复的血浆样品,以比较手动和自动方法。
    开发产生了一种新的自动化方法。对于自动化方法,对于手动方法,包含91%的总样品聚糖的聚糖峰显示小于5%的变化,而92%的总样品显示小于5%的变化。Passing-Bablok回归的结果表明12个聚糖峰(GP)的自动和手动方法之间没有差异。然而,对于8个GP存在系统差异,而四个全科医生存在系统和比例差异。
    开发的用于IgG聚糖分析的自动化样品制备方法减少了对危险化学品的暴露,并提供了简化的工作流程。尽管方法之间略有不同,新的自动化方法显示出高精度,并被证明与手动方法高度可比。
    UNASSIGNED: Glycomics, focusing on the role of glycans in biological processes, particularly their influence on the folding, stability and receptor interactions of glycoconjugates like antibodies, is vital for our understanding of biology. Changes in immunoglobulin G (IgG) N-glycosylation have been associated with various physiological and pathophysiological conditions. Nevertheless, time-consuming manual sample preparation is one of the limitations in the glycomics diagnostic implementation. The study aimed to develop an automated method for sample preparation on the Tecan Freedom Evo 200 platform and compare its efficiency and precision with the manual counterpart.
    UNASSIGNED: The initial method development included 32 pooled blood plasma technical replicates. An additional 24 pooled samples were used in the method comparison along with 78 random duplicates of plasma samples collected from 10,001 Dalmatians biobank to compare the manual and automated methods.
    UNASSIGNED: The development resulted in a new automated method. For the automated method, glycan peaks comprising 91% of the total sample glycan showed a variation of less than 5% while 92% of the total sample showed a variation of less than 5% for the manual method. The results of the Passing-Bablok regression indicated no differences between the automated and manual methods for 12 glycan peaks (GPs). However, for 8 GPs systematic difference was present, while both systematic and proportional differences were present for four GPs.
    UNASSIGNED: The developed automated sample preparation method for IgG glycan analysis reduced exposure to hazardous chemicals and offered a simplified workflow. Despite slight differences between the methods, the new automated method showed high precision and proved to be highly comparable to its manual counterpart.
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  • 文章类型: Journal Article
    抗菌药敏试验(ASTs)在对抗多重耐药病原体方面至关重要,然而它们可能很耗时,劳动密集型,和不稳定。以替加环素治疗脓毒症的AST为主要模型,在这里,我们建立了一个自动化的临床抗菌药物敏感性测试拉曼测定系统(CAST-R),基于D2O探测的拉曼光谱。具有用于样品预处理的液体机器人和用于数据采集和质量控制的基于机器学习的控制方案,3-h,自动化CAST-R工艺将AST加速>10倍,过程96平行的抗生素暴露反应,并产生高质量的拉曼光谱。通过代谢活性的加速最小抑制浓度被提出作为基于代谢的AST的定量和广泛适用的参数,在100个鲍曼不动杆菌分离株上进行测试时,与肉汤微量稀释法(BMD)显示出99%的基本一致性和93%的分类一致性。对26份临床阳性血液样本进行8种抗菌药物的进一步检测,包括替加环素,美罗培南,头孢他啶,氨苄西林/舒巴坦,苯唑西林,克林霉素,万古霉素,左氧氟沙星与基于BMD的结果具有93%的分类一致性。自动化,速度,可靠性,CAST-R的普遍适用性表明其在指导抗菌药物临床使用方面的潜在效用。
    Antimicrobial susceptibility tests (ASTs) are pivotal in combating multidrug resistant pathogens, yet they can be time-consuming, labor-intensive, and unstable. Using the AST of tigecycline for sepsis as the main model, here we establish an automated system of Clinical Antimicrobials Susceptibility Test Ramanometry (CAST-R), based on D2O-probed Raman microspectroscopy. Featuring a liquid robot for sample pretreatment and a machine learning-based control scheme for data acquisition and quality control, the 3-h, automated CAST-R process accelerates AST by >10-fold, processes 96 paralleled antibiotic-exposure reactions, and produces high-quality Raman spectra. The Expedited Minimal Inhibitory Concentration via Metabolic Activity is proposed as a quantitative and broadly applicable parameter for metabolism-based AST, which shows 99% essential agreement and 93% categorical agreement with the broth microdilution method (BMD) when tested on 100 Acinetobacter baumannii isolates. Further tests on 26 clinically positive blood samples for eight antimicrobials, including tigecycline, meropenem, ceftazidime, ampicillin/sulbactam, oxacillin, clindamycin, vancomycin, and levofloxacin reveal 93% categorical agreement with BMD-based results. The automation, speed, reliability, and general applicability of CAST-R suggest its potential utility for guiding the clinical administration of antimicrobials.
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  • 文章类型: Journal Article
    实验室管理自动化对于实现实验研究领域的互操作性和加速科学发现至关重要。资源的整合和跨组织的知识共享使科学发现能够通过提高实验室的生产率而加速。优化融资效率,并应对新出现的全球挑战。本文提出了一种通过《世界阿凡达》实现研究实验室数字化和自动化管理的新框架,一个包罗万象的动态知识图谱。这个数字实验室框架作为一个灵活的工具,使用户能够有效地利用来自不同系统和格式的数据,而不局限于特定的软件或协议。建立专门的本体和代理,并将其与QR码等技术相结合,RFID标签,和移动应用程序,使我们能够开发模块化应用程序,解决与实验室管理相关的一些关键挑战。这里,我们展示了用于爆炸性化学品的自动跟踪和干预系统,以及用于资产管理和信息检索的易于使用的移动应用程序。实施这些,我们已经实现了BIM和BMS数据与实验室清单和化学知识的语义链接。我们的方法可以捕获关键数据点并减少库存处理时间。所有数据来源均按照公平原则记录,确保其可访问性和互操作性。
    Laboratory management automation is essential for achieving interoperability in the domain of experimental research and accelerating scientific discovery. The integration of resources and the sharing of knowledge across organisations enable scientific discoveries to be accelerated by increasing the productivity of laboratories, optimising funding efficiency, and addressing emerging global challenges. This paper presents a novel framework for digitalising and automating the administration of research laboratories through The World Avatar, an all-encompassing dynamic knowledge graph. This Digital Laboratory Framework serves as a flexible tool, enabling users to efficiently leverage data from diverse systems and formats without being confined to a specific software or protocol. Establishing dedicated ontologies and agents and combining them with technologies such as QR codes, RFID tags, and mobile apps, enabled us to develop modular applications that tackle some key challenges related to lab management. Here, we showcase an automated tracking and intervention system for explosive chemicals as well as an easy-to-use mobile application for asset management and information retrieval. Implementing these, we have achieved semantic linking of BIM and BMS data with laboratory inventory and chemical knowledge. Our approach can capture the crucial data points and reduce inventory processing time. All data provenance is recorded following the FAIR principles, ensuring its accessibility and interoperability.
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  • 文章类型: Journal Article
    背景:我们比较了WantaiWan200+(WantaiBioPharm,北京,中国)关于帕多瓦大学医院(AOPD)使用的其他方法,意大利。方法:5027份剩余样本的血浆(P)或血清(S),从2023年5月至9月收集,在-20℃下进行分析或冷冻。贝克曼DXI800(DXI),罗氏Cobas8000e801(RC),SnibeMaglumi4000plus(SM),在AOPD处使用DiaSorinLiaxXL(DL)和结合位点Optilite(BS)设备。P-降钙素原(PCT),DXI;P-肌钙蛋白I(TnI),DXI;S-CA125,DXI;无SPSA(f-PSA),DXI;S-总PSA(t-PSA),DXI;S-IL6,SM;P-肌钙蛋白T(TnT),RC;P-NT-proBNP,RC;P-神经元特异性烯醇化酶(NSE),RC;S-CA15-3,DL;S-CA19-9,DL;S-AFP,DL;和S-CEA,在新鲜样品中测试DL。P-肌红蛋白(Myo),DXI;P-Cyfra21-1,RC;S-β2微球蛋白(B2MIC),BS;S-HE4,SM;S-PGI,SM;S-PGII,在冷冻和解冻样品中分析SM;S-CA72-4,SM;和S-CA50,SM。Bland-Altman(BA),Passing-Bablok(PB)和Cohen的Kappa(CKa)指标被用作统计数据。结果:发现11种分析物具有极好的可比性。例如,t-PSACKa为0.94(95CI:0.90至0.98),PB斜率和截距分别为1.02(95CI:0.99至1.03)和0.02(95CI:0.01至0.03),BA偏倚分别为2.25(95CI:-0.43至4.93)。十个测试的被测对象显示出次优的可比性。评估EFLM(EuBIVAS)性能规格的生物学差异,以评估所测量偏差的临床相关性。结论:对万泰万200+\性能的评估表明,方法之间的差异没有超过计算的偏差。计量可追溯性可能会影响某些被测对象的比较。
    Background: We compared the performance of 21 different assays performed by the Wantai Wan200+ (Wantai BioPharm, Beijing, China) with respect to other methods in use at the University Hospital of Padova (AOPD), Italy. Methods: The plasma (P) or serum (S) of 5027 leftover samples, collected from May to Sept 2023, was either analyzed or frozen at -20 °C. Beckman DXI800 (DXI), Roche Cobas 8000 e801 (RC), Snibe Maglumi 4000 plus (SM), DiaSorin Liaison XL (DL) and Binding Site Optilite (BS) equipment were used at the AOPD. P-procalcitonin (PCT), DXI; P-Troponin I (TnI), DXI; S-CA125, DXI; S-free PSA (f-PSA), DXI; S-total PSA (t-PSA), DXI; S-IL6, SM; P-Troponin T (TnT), RC; P-NT-proBNP, RC; P-Neuron-Specific Enolase (NSE), RC; S-CA15-3, DL; S-CA19-9, DL; S-AFP, DL; and S-CEA, DL were tested in fresh samples. P-Myoglobin (Myo), DXI; P-Cyfra21-1, RC; S-β2 microglobulin (B2MIC), BS; S-HE4, SM; S-PGI, SM; S-PGII, SM; S-CA72-4, SM; and S-CA50, SM were analyzed in frozen and thawed samples. Bland-Altman (BA), Passing-Bablok (PB) and Cohen\'s Kappa (CKa) metrics were used as statistics. Results: An excellent comparability profile was found for 11 analytes. For example, the t-PSA CKa was 0.94 (95%CI: 0.90 to 0.98), and the PB slope and intercept were 1.02 (95%CI: 0.99 to 1.03) and 0.02 (95%CI: 0.01 to 0.03), respectively; the BA bias was 2.25 (95%CI: -0.43 to 4.93). Ten tested measurands demonstrated a suboptimal comparability profile. Biological variation in EFLM (EuBIVAS) performance specifications was evaluated to assess the clinical relevance of measured biases. Conclusions: Evaluation of the Wantai Wan200+\'s performance suggests that between-method differences did not exceed the calculated bias. Metrological traceability may influence the comparisons obtained for some measurands.
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