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=What are the key elements of a LIMS for food and beverage testing?=
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'''Title''': ''What are the key elements of a LIMS for food and beverage testing?''
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'''Author for citation''': Shawn E. Douglas
==Sandbox begins below==
 
{{raw:wikipedia::Detection limit}}
'''License for content''': [https://creativecommons.org/licenses/by-sa/4.0/ Creative Commons Attribution-ShareAlike 4.0 International]
 
'''Publication date''': September 2022
 
==Introduction==
A food and beverage [[laboratory]] may analyze anything from ingredients and additives to finalized food and beverage products, and many things in between. The types of analyses associated with these and other substrates and matrices can be equally diverse, depending on the role the food and beverage laboratory is playing in the overall larger framework of the industry. As has been noted in other work, the lab work of the research and development (R&D) role, for example, may look different than that of the food and beverage lab conducting activities in the pre-manufacturing/manufacturing role and the post-production regulation and security role.<ref name="DouglasWhatTypes22">{{cite web |url=https://www.limswiki.org/index.php/LIMS_FAQ:What_types_of_testing_occur_within_a_food_and_beverage_laboratory? |title=What types of testing occur within a food and beverage laboratory? |author=Douglas, S.E. |publisher=LIMSwiki |date=24 August 2022 |accessdate=12 September 2022}}</ref>
 
Among all these activities is the driving goal of better ensuring a safer, more high-quality food and beverage product for consumers. This goal is furthered by the industry's past lessons and regulatory considerations that were made as a result of those lessons.<ref name="DouglasWhatIs22">{{cite web |url=https://www.limswiki.org/index.php/LIMS_FAQ:What_is_the_importance_of_a_food_and_beverage_testing_laboratory_to_society%3F |title=What is the importance of a food and beverage testing laboratory to society? |author=Douglas, S.E. |publisher=LIMSwiki |date=16 August 2022 |accessdate=12 September 2022}}</ref> However, these regulatory requirements place an additional burden on labs trying to meet this common goal, as well as their own internal goals towards quality and excellence. This broad array of analytical techniques and set of regulatory considerations means such labs will continue to turn to [[Informatics (academic field)|informatics]] solutions like the [[laboratory information management system]] (LIMS) and other food safety software, in turn requiring those [[information management]] solutions reliably meet the unique needs of their lab.
 
This brief topical article will examine the typical food and beverage lab's operations and workload, and suggest a base set of LIMS functionality (i.e., system requirements) that is critical to fulfilling the information management and [[workflow]] requirements of this lab type. Additional unique requirements will also be briefly discussed.
 
'''Note''': Any citation leading to a software vendor's site is not to be considered a recommendation for that vendor. The citation should however still stand as a representational example of what vendors are implementing in their systems.
 
==Food and beverage laboratory workflow, workload, and information management==
An earlier work looked at the type of testing occurring in food and beverage labs. That examination revealed a wide array of activities going on within the industry, depending on the role the lab plays within the industry, including analyses for innovative improvement, aroma/flavor, nutritional reformulation, stability, packaging safety, labeling, quality control, authenticity, and accreditation.<ref name="DouglasWhatTypes22" /> For example, improving the flavor of plant-based meat substitutes comes with somewhat different analytical techniques and disciplinary requirements than improving the three-dimensional food printing of said meat substitutes.<ref name="PatelBev21">{{cite web |url=https://spectrum.ieee.org/3d-printed-meat |title=Beyond Burgers: Animal and Plant Cells Combined for 3D-Printed Steaks |author=Patel, P. |work=IEEE Spectrum |date=18 February 2021 |accessdate=12 September 2022}}</ref> Further, both of these R&D workflows likely differ significantly from the food and beverage lab testing for contaminants in a finished product. When you also take into consideration that "[e]very food supply chain will have its own set of product specifications and QC parameters,"<ref name="SmithInteg19">{{cite web |url=https://foodsafetytech.com/feature_article/integrated-informatics-optimizing-food-quality-and-safety-by-building-regulatory-compliance-into-the-supply-chain/ |title=Integrated Informatics: Optimizing Food Quality and Safety by Building Regulatory Compliance into the Supply Chain |author=Smith, K. |work=Food Safety Tech |date=02 July 2019 |accessdate=12 September 2022}}</ref> the workflow picture gets even more complex. Undoubtedly, this means a significant diversity in workflow and workload considerations for the wide variety of industry labs out there.
 
What is more certain about all these labs' workflows and workloads is the need for quality and consistency to be woven into them in the name of consumer safety and satisfaction, as well as regulatory compliance. At every step of the way—despite any differences in analyses, substrates, and instrumentation among these labs—is this common need to ensure safety, quality, and compliance as part of the end result of operations. The lab attempting to improve the flavor profile of a blended wine may depend on a variety of complex chemical analyses to monitor acids<ref>{{Cite journal |last=Ivanova-Petropulos |first=Violeta |last2=Tašev |first2=Krste |last3=Stefova |first3=Marina |date=2016-12-27 |title=HPLC method validation and application for organic acid analysis in wine after solid-phase extraction |url=http://www.mjcce.org.mk/index.php/MJCCE/article/view/1073 |journal=Macedonian Journal of Chemistry and Chemical Engineering |volume=35 |issue=2 |pages=225 |doi=10.20450/mjcce.2016.1073 |issn=1857-5625}}</ref>, while the lab attempting to verify the heavy metal content in spinach will use a different set of analytical technique and equipment<ref>{{Cite journal |last=Ng |first=Chuck Chuan |last2=Rahman |first2=Md Motior |last3=Boyce |first3=Amru Nasrulhaq |last4=Abas |first4=Mhd Radzi |date=2016-12 |title=Heavy metals phyto-assessment in commonly grown vegetables: water spinach (I. aquatica) and okra (A. esculentus) |url=http://springerplus.springeropen.com/articles/10.1186/s40064-016-2125-5 |journal=SpringerPlus |language=en |volume=5 |issue=1 |pages=469 |doi=10.1186/s40064-016-2125-5 |issn=2193-1801 |pmc=PMC4833764 |pmid=27119073}}</ref>; however, both labs are focused on performing the activities with some form of safety, quality, and compliance in mind. As such, this article won't look further at specific workflows but rather look more broadly at ensuring those workflows are more optimal, especially through the effective use of information management solutions like a LIMS.
 
===LIMS===
The use of LIMS in food production facilities and labs is not a new concept.<ref>{{Cite journal |last=Çağındı |first=Özlem |last2=Ötleş |first2=Semih |date=2004-12 |title=Importance of laboratory information management systems (LIMS) software for food processing factories |url=https://linkinghub.elsevier.com/retrieve/pii/S0260877404000846 |journal=Journal of Food Engineering |language=en |volume=65 |issue=4 |pages=565–568 |doi=10.1016/j.jfoodeng.2004.02.021}}</ref> However, little information can be found as to the percentage of today's food and beverage laboratories using a LIMS in their workflow. Several surveys from 2020, however, hint that LIMS are important to these types of labs. A survey of 135 professionals—nine percent of them from the food and beverage industry—from laboratory consultancy Astrix Technology found that more than 77 percent of respondents had at least one LIMS implemented in their organization.<ref name="Astrix2020LIMS">{{cite web |url=https://astrixinc.com/wp-content/uploads/2021/03/Astrix-2020-LIMS-Market-Research-Report.pdf |format=PDF |title=Astrix 2020 LIMS Market Research Survey Report |publisher=Astrix Technology, LLC |date=March 2021 |accessdate=12 September 2022}}</ref> A separate survey from ''Lab Manager'' about analytical instrument use among readers found that more than 16 percent of them were using instruments for food and beverage analysis.<ref name="Crawford-BrownResults20">{{cite web |url=https://www.labmanager.com/surveys/results-from-the-lab-manager-analytical-instrument-survey-22109 |title=Results from the Lab Manager Analytical Instrument Survey |work=Lab Manager |author=Crawford-Brown, C. |date=25 March 2020 |accessdate=12 September 2022}}</ref> Combined, these surveys suggest that the food and beverage industry is not trivially represented among labs. By extension—and particularly given the importance of integrating instrumentation and their produced data in such an environment<ref name="SmithInteg19" /><ref name="ApteIsYour20">{{cite web |url=https://foodsafetytech.com/column/is-your-food-testing-lab-prepping-for-an-iso-iec-17025-audit/ |title=Is Your Food Testing Lab Prepping for an ISO/IEC 17025 Audit? |author=Apte, A. |work=Food Safety Tech |date=20 October 2020 |accessdate=12 September 2022}}</ref><ref name="SiemensProcess22">{{cite web |url=https://assets.new.siemens.com/siemens/assets/api/uuid:ca5438d3-5b52-4b41-aae0-aaaa3685484e/pibr-00021-0820-food-bev-portrait.pdf |format=PDF |title=Food & Beverage Process Automation and Instrumentation |publisher=Siemens Industry, Inc |date=2022 |accessdate=12 September 2022}}</ref>—a LIMS or other informatics solution appears to be increasingly critical to eliminating manual processes, improving sample management, increasing productivity, and improving regulatory conformance.<ref name="Astrix2020LIMS" /> This, of course, lends to the food and beverage lab's focus on safety, quality, and compliance.
 
A LIMS can improve laboratory workflows and workloads while enhancing safety, quality, and compliance in a number of ways. A fragmented mix of paper-based and electronic information sources can be a detriment to the traceability of or rapid accessibility to ingredients, additives, quality control samples, standard operating procedures (SOPs), environmental monitoring data, chain of custody data, and other vital aspects of food and beverage production. A well-implemented LIMS can reduce the silos of information and data, while at the same time make that information and data more secure and readily accessible. Given the regulatory demands for providing rapid proof of traceable product movement and relevant quality control data, the LIMS acts as the central integrator and audit trail for that information.<ref name="SmithInteg19" /><ref name="McDermottHowDig18">{{cite web |url=https://foodsafetytech.com/column/how-digital-solutions-support-supply-chain-transparency-and-traceability/ |title=How Digital Solutions Support Supply Chain Transparency and Traceability |author=McDermott, P. |work=Food Safety Tech |date=31 July 2018 |accessdate=13 September 2022}}</ref><ref name="EvansTheDig19">{{cite web |url=https://foodsafetytech.com/feature_article/the-digital-transformation-of-global-food-security/ |title=The Digital Transformation of Global Food Security |author=Evans, K. |work=Food Safety Tech |date=15 November 2019 |accessdate=13 September 2022}}</ref> Because the LIMS improves traceability—including through its automated interfaces with instruments and other data systems—real-time monitoring of supply chain issues, quality control data, instrument use, and more is further enabled, particularly when paired with configurable dashboards and alert mechanisms. By extension, food and beverage producers can more rapidly act on insights gained from those real-time dashboards.<ref name="SmithInteg19" /> This is also means that the food and beverage testing lab can react more rapidly to issues that compromise compliance with certification to the [[ISO 17025]] standard or Food and Drug Administration (FDA) [[LII:FDA Food Safety Modernization Act Final Rule on Laboratory Accreditation for Analyses of Foods: Considerations for Labs and Informatics Vendors|Food Safety Modernization Act]] (FSMA) requirements.<ref name="ApteIsYour20" /><ref name="PaszkoTrace15">{{cite web |url=https://foodsafetytech.com/feature_article/traceability-leveraging-automation-to-satisfy-fsma-requirements/ |title=Traceability: Leveraging Automation to Satisfy FSMA Requirements |author=Paszko, C. |work=Food Safety Tech |date=19 August 2015 |accessdate=13 September 2022}}</ref><ref name="PaszkoHow15">{{cite web |url=https://foodsafetytech.com/feature_article/how-lims-facilitates-iso-17025-certification-in-food-testing-labs/ |title=How LIMS Facilitates ISO 17025 Certification in Food Testing Labs |author=Paszko, C. |work=Food Safety Tech |date=26 October 2015 |accessdate=13 September 2022}}</ref><ref name="DanielsUsing17">{{cite web |url=https://foodsafetytech.com/column/using-lims-get-shape-fdas-visit/ |title=Using LIMS to Get In Shape for FDA’s Visit |author=Daniels, T. |work=Food Safety Tech |date=22 March 2017 |accessdate=13 September 2022}}</ref> Finally, many modern LIMS tailored to the food and beverage industry come pre-configured out of the box with analytical and quality control workflow support tools that can be further optimized to a lab's unique workflow.<ref name="IngallsHowAdv20">{{cite web |url=https://foodsafetytech.com/feature_article/how-advanced-lims-brings-control-consistency-and-compliance-to-food-safety/ |title=How Advanced LIMS Brings Control, Consistency and Compliance to Food Safety |author=Ingalls, E. |work=Food Safety Tech |date=06 August 2020 |accessdate=13 September 2022}}</ref>
 
===Other informatics options===
As an aside, it must be noted that the LIMS is not the sole information management solution for food and beverage producers and laboratories. Software-based information management solutions are being marketed to food and beverage labs in other ways. Some vendors have taken to marketing the somewhat related [[laboratory execution system]] (LES), which tends to focus more on laboratory test method execution at the process level while integrating other R&D functionalities found in, for example, [[electronic laboratory notebook]]s (ELNs).<ref name="iVentionLES">{{cite web |url=https://hs.iles.cloud/en/food-and-beverages-lab-execution |title=iLES Food & Beverages Lab Execution |publisher=iVention BV |accessdate=12 September 2022}}</ref><ref name="LVSHowLIMS20">{{cite web |url=https://www.news-medical.net/whitepaper/20200416/How-LIMS-can-Improve-your-Food-and-Beverage-Testing-Lab.aspx |title=How LIMS can Improve your Food and Beverage Testing Lab |author=LabVantage Solutions |work=News Medical |date=16 April 2020 |accessdate=12 September 2022}}</ref> Other vendors have moved away from the "LIMS" and "LES" moniker completely, referring to their software as simply "food safety software." These offerings appear to focus on helping a producer do more than manage laboratory testing output by addressing other organizational needs such as developing regulatory-driven safety plans, generating schedules for environmental testing, improving communication and compliance, improving reaction time to non-conformances, improving audit readiness and reporting, ensuring greater compliance, and identifying trends across the entire enterprise.<ref name="CorviumWhatIs19">{{cite web |url=https://corvium.com/what-is-a-food-intelligence-platform-lims-vs-food-safety-software/ |title=What Is a Food Intelligence Platform? LIMS vs. Food Safety Software |publisher= |date=09 May 2019 |accessdate=12 September 2022}}</ref><ref name="FLQSafety">{{cite web |url=https://www.foodlogiq.com/solutions/safety-and-quality/ |title=Safety & Quality Management |publisher=FoodLogiQ |accessdate=12 September 2022}}</ref><ref name="SCFoodSafety">{{cite web |url=https://safetychain.com/food-safety-software/ |title=Food Safety Software |publisher=SafetyChain Software, Inc |accessdate=12 September 2022}}</ref><ref name="F3AgTechBest">{{cite web |url=https://agtech.folio3.com/food-safety-software/ |title=Best Food Safety Software For Quality Management Of Food |publisher=Folio3 Software, Inc |accessdate=12 September 2022}}</ref><ref name="FDAIPower">{{cite web |url=https://www.fooddocs.com/ |title=FoodDocs: AI-Powered Food Safety System with a HACCP builder |publisher=FoodDocs |accessdate=12 September 2022}}</ref> In comparison, some LIMS may or may not address these issues; this functionality will be discussed further in the section on specialty LIMS requirements.
 
==Base LIMS requirements==
Given the above, it's clear LIMS adoption and use is important to the continued success of food and beverage labs. However, in most cases, a generic LIMS won't do; it's imperative the lab find a solution that meets all or most of its workflow requirements. This more often than not requires a configurable solution that enables trained users to quickly make the changes they need, if those changes make sense within the overall data structure of the LIMS.
 
What follows is a list of system functionality important to most any food and beverage laboratory, with a majority of that functionality found in many vendor software solutions.<ref name="SmithInteg19" /><ref name="ApteIsYour20" /><ref name="McDermottHowDig18" /><ref name="EvansTheDig19" /><ref name="IngallsHowAdv20" /><ref name="iVentionLES" /><ref name="StarlimsFood22">{{cite web |url=https://www.starlims.com/wp-content/uploads/food-and-bev-lims-spec-document.pdf |format=PDF |title=STARLIMS Food and Beverage Industry LIMS Specification Document |publisher=STARLIMS Corporation |date=November 2021 |accessdate=14 September 2022}}</ref>
 
'''Test, sample and result management'''
 
*Sample log-in and management, with support for unique IDs
*Sample batching
*[[Barcode]] and RFID support
*End-to-end sample and inventory tracking
*Pre-defined and configurable industry-specific test and method management, including for bacteria (i.e., microbiology), heavy metals (i.e., chemistry), drug residues (i.e., pharmaceutical chemistry), and other substances
*Pre-defined and configurable industry-specific workflows
*Configurable screens and data fields
*Specification management
*Test, sampling, instrument, etc. scheduling and assignment
*Test requesting
*Data import and export
*Robust query tools
*Analytical tools, including [[data visualization]], statistical analysis, and [[data mining]] tools
*Document and image management
*Version control
*Project management
*Method and protocol management
*Investigation management
*Facility and sampling site management
*Storage management and monitoring
 
'''Quality, security, and compliance'''
 
*[[Quality assurance]] / [[quality control]] mechanisms
*Mechanisms for compliance with ISO 17025 and HACCP, including support for critical control point (CCP) specifications and limits
*Results, method, protocol, batch, and material validation, review, and release
*Data validation
*Trend and control charts for statistical analysis and measurement of uncertainty
*User qualification, performance, and training management
*[[Audit trail]]s and [[chain of custody]] support
*Configurable and granular role-based security
*Configurable system access and use (authentication requirements, account usage rules, account locking, etc.)
*[[Electronic signature]] support
*Data [[encryption]] and secure communication protocols
*Archiving and [[Data retention|retention]] of data and information
*Configurable data [[backup]]s
*Status updates and alerts
*Environmental monitoring support
*Incident and non-conformance notification, tracking, and management
 
'''Operations management and reporting'''
 
*Configurable dashboards for monitoring, by product, process, facility, etc.
*Customizable rich-text reporting, with multiple supported output formats
*Custom and industry-specific reporting, including certificates of analysis (CoAs) ...
*Industry-compliant labeling
*Email integration
*Instrument interfacing and data management
*Third-party software interfacing (e.g., LES, scientific data management system [SDMS], other database)
*Data import, export, and archiving
*Instrument calibration and maintenance tracking
*Inventory and material management
*Supplier/vendor/customer management
*Integrated (or online) system help
 
==Specialty LIMS requirements==
As noted previously, some software vendors are addressing food and beverage processor needs beyond the laboratory through their food safety software. A standard LIMS tailored for the food and beverage industry may already contribute to some of these wider organizational functions, but many may not, or may vary in what additional functionality they provide. In that regard, a food and beverage LIMS vendor may also include specialized functionality that helps the food and beverage producer and its laboratory<ref name="CorviumWhatIs19" /><ref name="iVentionLES" /><ref name="StarlimsFood22" /><ref name="Douglas>{{Cite web |last=Douglas, S.E. |date=May 2022 |title=17. Production management |work=LIMSpec 2022 R1 |url=https://www.limswiki.org/index.php?title=LII:LIMSpec/Specialty_Laboratory_Functions#17._Production_management |publisher=LIMSwiki.org |accessdate=14 September 2022}}</ref>:
 
*Manage stability studies:
*Manage recipes, as well as master and batch production records:
*'''Take advantage of ELN functionality''':  Given the level of R&D to be found in a food and beverage facility, the ELN is a familiar companion to other informatics systems. A few LIMS vendors may have a built-in ELN with their LIMS or offer an ELN that comes readily integrated with the LIMS. Some elements of ELN functionality may even be found in a few solutions. At a minimum—and nodded to in the base functionality above—the LIMS should support ELN functionality through its ability to effectively connect to a third-party ELN.
*'''Develop regulatory-driven safety plans''': The Hazard Analysis and Critical Control Points (HACCP) quality control method is recommended or required for food and testing labs (and is an influence on ISO 17025). Some LIMS vendors have recognized this and integrated support for building HACCP steps into laboratory workflows. In some cases this may be as sophisticated as allowing the user to diagram HACCP in their lab or facility as a visualization tool.
*'''Generate schedules for environmental testing''': While a LIMS can help assign and schedule a variety of laboratory tasks, broader organizational goals of testing the production environment on a scheduled, reportable basis may not be so straightforward, particularly without facility and sampling site management functionality that allows for highlighting specific test points in the facility. Even offsite or randomized testing may not be fully supported by a generic LIMS, requiring a LIMS flexible enough to compensate for the need for broader scheduled and randomized testing and retesting.
*Improve communication and compliance:
*'''Improve reaction time to non-conformances''': Many LIMS will have some basic form of non-conformance and incident management tools, but the robustness and extensibility of that functionality may be lacking. Can it send an SMS or email to the appropriate supplier in real-time when a pre-defined set of circumstances concerning that supplier's ingredients occurs? Can it re-prioritize or pause other related activities that are scheduled due to the identified non-conformance or incident? This is a useful area of functionality for the potential LIMS buyer to confirm with a vendor.
*Improve audit readiness and reporting:
*Ensure greater regulatory compliance:
 
==Conclusion==
This brief topical article sought to answer "what are the key elements of a LIMS for food and beverage testing??" It notes that ...
 
* LIMS and agriculture genotyping workflows: https://pubmed.ncbi.nlm.nih.gov/16914063/
* Data management systems in the food industry: https://link.springer.com/chapter/10.1007/978-1-4939-0311-5_3
* Manufacturing execution system in food and beverage: https://www.sciencedirect.com/science/article/abs/pii/S0260877420300315
 
==References==
{{Reflist|colwidth=30em}}
 
<!---Place all category tags here-->
[[Category:LIMS FAQ articles (added in 2022)]]
[[Category:LIMS FAQ articles (all)]]
[[Category:LIMS FAQ articles on food and beverage]]

Latest revision as of 18:25, 10 January 2024

Sandbox begins below

Template:Short description

The limit of detection (LOD or LoD) is the lowest signal, or the lowest corresponding quantity to be determined (or extracted) from the signal, that can be observed with a sufficient degree of confidence or statistical significance. However, the exact threshold (level of decision) used to decide when a signal significantly emerges above the continuously fluctuating background noise remains arbitrary and is a matter of policy and often of debate among scientists, statisticians and regulators depending on the stakes in different fields.

Significance in analytical chemistry

In analytical chemistry, the detection limit, lower limit of detection, also termed LOD for limit of detection or analytical sensitivity (not to be confused with statistical sensitivity), is the lowest quantity of a substance that can be distinguished from the absence of that substance (a blank value) with a stated confidence level (generally 99%).[1][2][3] The detection limit is estimated from the mean of the blank, the standard deviation of the blank, the slope (analytical sensitivity) of the calibration plot and a defined confidence factor (e.g. 3.2 being the most accepted value for this arbitrary value).[4] Another consideration that affects the detection limit is the adequacy and the accuracy of the model used to predict concentration from the raw analytical signal.[5]

As a typical example, from a calibration plot following a linear equation taken here as the simplest possible model:

where, corresponds to the signal measured (e.g. voltage, luminescence, energy, etc.), "Template:Mvar" the value in which the straight line cuts the ordinates axis, "Template:Mvar" the sensitivity of the system (i.e., the slope of the line, or the function relating the measured signal to the quantity to be determined) and "Template:Mvar" the value of the quantity (e.g. temperature, concentration, pH, etc.) to be determined from the signal ,[6] the LOD for "Template:Mvar" is calculated as the "Template:Mvar" value in which equals to the average value of blanks "Template:Mvar" plus "Template:Mvar" times its standard deviation "Template:Mvar" (or, if zero, the standard deviation corresponding to the lowest value measured) where "Template:Mvar" is the chosen confidence value (e.g. for a confidence of 95% it can be considered Template:Mvar = 3.2, determined from the limit of blank).[4]

Thus, in this didactic example:

There are a number of concepts derived from the detection limit that are commonly used. These include the instrument detection limit (IDL), the method detection limit (MDL), the practical quantitation limit (PQL), and the limit of quantitation (LOQ). Even when the same terminology is used, there can be differences in the LOD according to nuances of what definition is used and what type of noise contributes to the measurement and calibration.[7]

The figure below illustrates the relationship between the blank, the limit of detection (LOD), and the limit of quantitation (LOQ) by showing the probability density function for normally distributed measurements at the blank, at the LOD defined as 3 × standard deviation of the blank, and at the LOQ defined as 10 × standard deviation of the blank. (The identical spread along Abscissa of these two functions is problematic.) For a signal at the LOD, the alpha error (probability of false positive) is small (1%). However, the beta error (probability of a false negative) is 50% for a sample that has a concentration at the LOD (red line). This means a sample could contain an impurity at the LOD, but there is a 50% chance that a measurement would give a result less than the LOD. At the LOQ (blue line), there is minimal chance of a false negative.

Template:Wide image

Instrument detection limit

Most analytical instruments produce a signal even when a blank (matrix without analyte) is analyzed. This signal is referred to as the noise level. The instrument detection limit (IDL) is the analyte concentration that is required to produce a signal greater than three times the standard deviation of the noise level. This may be practically measured by analyzing 8 or more standards at the estimated IDL then calculating the standard deviation from the measured concentrations of those standards.

The detection limit (according to IUPAC) is the smallest concentration, or the smallest absolute amount, of analyte that has a signal statistically significantly larger than the signal arising from the repeated measurements of a reagent blank.

Mathematically, the analyte's signal at the detection limit () is given by:

where, is the mean value of the signal for a reagent blank measured multiple times, and is the known standard deviation for the reagent blank's signal.

Other approaches for defining the detection limit have also been developed. In atomic absorption spectrometry usually the detection limit is determined for a certain element by analyzing a diluted solution of this element and recording the corresponding absorbance at a given wavelength. The measurement is repeated 10 times. The 3σ of the recorded absorbance signal can be considered as the detection limit for the specific element under the experimental conditions: selected wavelength, type of flame or graphite oven, chemical matrix, presence of interfering substances, instrument... .

Method detection limit

Often there is more to the analytical method than just performing a reaction or submitting the analyte to direct analysis. Many analytical methods developed in the laboratory, especially these involving the use of a delicate scientific instrument, require a sample preparation, or a pretreatment of the samples prior to being analysed. For example, it might be necessary to heat a sample that is to be analyzed for a particular metal with the addition of acid first (digestion process). The sample may also be diluted or concentrated prior to analysis by means of a given instrument. Additional steps in an analysis method add additional opportunities for errors. Since detection limits are defined in terms of errors, this will naturally increase the measured detection limit. This "global" detection limit (including all the steps of the analysis method) is called the method detection limit (MDL). The practical way for determining the MDL is to analyze seven samples of concentration near the expected limit of detection. The standard deviation is then determined. The one-sided Student's t-distribution is determined and multiplied versus the determined standard deviation. For seven samples (with six degrees of freedom) the t value for a 99% confidence level is 3.14. Rather than performing the complete analysis of seven identical samples, if the Instrument Detection Limit is known, the MDL may be estimated by multiplying the Instrument Detection Limit, or Lower Level of Detection, by the dilution prior to analyzing the sample solution with the instrument. This estimation, however, ignores any uncertainty that arises from performing the sample preparation and will therefore probably underestimate the true MDL.

Limit of each model

The issue of limit of detection, or limit of quantification, is encountered in all scientific disciplines. This explains the variety of definitions and the diversity of juridiction specific solutions developed to address preferences. In the simplest cases as in nuclear and chemical measurements, definitions and approaches have probably received the clearer and the simplest solutions. In biochemical tests and in biological experiments depending on many more intricate factors, the situation involving false positive and false negative responses is more delicate to handle. In many other disciplines such as geochemistry, seismology, astronomy, dendrochronology, climatology, life sciences in general, and in many other fields impossible to enumerate extensively, the problem is wider and deals with signal extraction out of a background of noise. It involves complex statistical analysis procedures and therefore it also depends on the models used,[5] the hypotheses and the simplifications or approximations to be made to handle and manage uncertainties. When the data resolution is poor and different signals overlap, different deconvolution procedures are applied to extract parameters. The use of different phenomenological, mathematical and statistical models may also complicate the exact mathematical definition of limit of detection and how it is calculated. This explains why it is not easy to come to a general consensus, if any, about the precise mathematical definition of the expression of limit of detection. However, one thing is clear: it always requires a sufficient number of data (or accumulated data) and a rigorous statistical analysis to render better signification statistically.

Limit of quantification

The limit of quantification (LoQ, or LOQ) is the lowest value of a signal (or concentration, activity, response...) that can be quantified with acceptable precision and accuracy.

The LoQ is the limit at which the difference between two distinct signals / values can be discerned with a reasonable certainty, i.e., when the signal is statistically different from the background. The LoQ may be drastically different between laboratories, so another detection limit is commonly used that is referred to as the Practical Quantification Limit (PQL).

See also

References

  1. IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "detection limit".
  2. "Guidelines for Data Acquisition and Data Quality Evaluation in Environmental Chemistry". Analytical Chemistry 52 (14): 2242–49. 1980. doi:10.1021/ac50064a004. 
  3. Saah AJ, Hoover DR (1998). "[Sensitivity and specificity revisited: significance of the terms in analytic and diagnostic language."]. Ann Dermatol Venereol 125 (4): 291–4. PMID 9747274. https://pubmed.ncbi.nlm.nih.gov/9747274. 
  4. 4.0 4.1 "Limit of blank, limit of detection and limit of quantitation". The Clinical Biochemist. Reviews 29 Suppl 1 (1): S49–S52. August 2008. PMC 2556583. PMID 18852857. https://www.ncbi.nlm.nih.gov/pmc/articles/2556583. 
  5. 5.0 5.1 "R: "Detection" limit for each model" (in English). search.r-project.org. https://search.r-project.org/CRAN/refmans/bioOED/html/calculate_limit.html. 
  6. "Signal enhancement on gold nanoparticle-based lateral flow tests using cellulose nanofibers". Biosensors & Bioelectronics 141: 111407. September 2019. doi:10.1016/j.bios.2019.111407. PMID 31207571. http://ddd.uab.cat/record/218082. 
  7. Long, Gary L.; Winefordner, J. D., "Limit of detection: a closer look at the IUPAC definition", Anal. Chem. 55 (7): 712A–724A, doi:10.1021/ac00258a724 

Further reading

  • "Limits for qualitative detection and quantitative determination. Application to radiochemistry". Analytical Chemistry 40 (3): 586–593. 1968. doi:10.1021/ac60259a007. ISSN 0003-2700. 

External links

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