IWA 15:2015
(Main)Specification and method for the determination of performance of automated liquid handling systems
Specification and method for the determination of performance of automated liquid handling systems
IWA 15:2015 specifies methods for testing the volumetric performance of air-displacement, system-liquid filled and positive displacement automated liquid handling systems (ALHS), including an estimation of measurement uncertainties and established traceability to reference standards (preferably, traceability to SI Units). The testing methods specified in this document may also be used to measure the volumetric performance of automated liquid delivery systems which do not aspirate the test liquid. IWA 15:2015 also specifies statistical methods for the determination of random and systematic errors (including intra-plate and inter-plate comparisons), analysis of measured results when using multichannel dispensing heads, and analysis depending on dispense patterns. It further defines terms and formulae to be used for summarizing test results. IWA 15:2015 also specifies the information to be provided to users of ALHS, including the display of summary results and performance claims. IWA 15:2015 is applicable to all ALHS with complete, installed liquid handling devices, including tips and other essential parts needed for delivering a specified volume, which perform liquid handling tasks without human intervention into microplates. Manipulation of the microplates on the deck of the automated liquid handling system may be achieved automatically, semi-automatically, or manually. IWA 15:2015 addresses the needs of: - suppliers of ALHS, as a basis for quality control including, where appropriate, the issuance of supplier's declarations; - test houses and other bodies, as a basis for independent certification and calibration; - users of the equipment, to enable calibration, verification, validation, and routine testing of trueness and precision. The tests established in this IWA should be carried out by trained personnel.
Spécification et méthode pour la détermination de performance des systèmes automatisés de manipulation de liquides
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Standards Content (Sample)
INTERNATIONAL IWA
WORKSHOP 15
AGREEMENT
First edition
2015-10-15
Specification and method for the
determination of performance of
automated liquid handling systems
Spécification et méthode pour la détermination de performance des
systèmes automatisés de manipulation de liquides
Reference number
IWA 15:2015(E)
©
ISO 2015
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IWA 15:2015(E)
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IWA 15:2015(E)
Contents Page
Foreword .v
1 Scope .1
2 Normative references .1
3 Terms and definitions .1
3.1 Definitions . 2
3.2 Abbreviated terms . 8
4 Operation of automated liquid handling systems .9
4.1 Types of automated liquid handling systems . 9
4.1.1 Types of piston operated automated liquid handling systems . 9
4.1.2 Types of other (pump operated) automated liquid handling systems. 9
4.2 Adjustment .10
4.2.1 Need for adjustment .10
4.2.2 Liquid classes .10
4.2.3 Adjustment of ALHS settings .10
4.3 Tips .10
4.3.1 General.10
4.3.2 Air-displacement tips .10
4.3.3 Positive displacement tips .11
4.3.4 Fixed tips.11
4.4 Environmental conditions .11
4.4.1 Discussion and recommendations.11
4.4.2 Factory acceptance testing .11
4.4.3 Site acceptance and user testing .12
5 Volumetric performance .12
5.1 Introductory discussion .12
5.2 Data collection and examination .14
5.3 Indexing to track data .15
5.3.1 Indexing from the channel perspective .15
5.3.2 Indexing from the microplate perspective .15
5.4 Descriptive statistics on an individual channel basis .16
5.5 Descriptive statistics on a run order basis .18
5.6 Descriptive statistics for entire data sets .18
5.7 Differences between channels .19
5.8 Handling of sub-deliveries .19
6 Measurement methods .20
6.1 Overview of methods suitable for measuring ALHS performance .20
6.2 Methods for use with any ALHS platform (open methods) .29
6.2.1 Ratiometric photometry .29
6.2.2 Gravimetry, single channel measurement .29
6.2.3 Gravimetry, full-plate measurement for correlation with photometry .29
6.2.4 Gravimetric regression method for low volumes .30
6.2.5 Photometry using Orange G .30
6.2.6 Hybrid method: gravimetry and photometry with Tartrazine . .30
6.2.7 Hybrid method: photometry and gravimetry with p-nitrophenol .31
6.2.8 Hybrid method: gravimetry and photometry with Ponceau S .31
6.2.9 Pressure sensing .31
6.2.10 Calorimetric measurement .31
6.2.11 Optical image analysis .31
6.3 Methods specific to an ALHS model or accessory (closed methods) .32
6.3.1 Gravimetry and hybrid method: gravimetry and photometry .32
6.3.2 Photometry with Tartrazine .32
7 Specification of ALHS volumetric performance .33
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IWA 15:2015(E)
7.1 Mandatory information to be supplied by manufacturer .33
7.2 Optional information that can be supplied by manufacturer .33
8 Reporting .34
8.1 Reporting the results .34
8.1.1 General.34
8.1.2 Test reports and calibration certificates .34
8.1.3 Calibration certificates.35
9 Potential future work .36
Annex A (informative) Applications of descriptive statistics .38
Annex B (informative) Test methods for ALHS performance .50
Annex C (normative) Calculation of liquid volumes from balance readings .114
Annex D (informative) Workshop contributors .116
Bibliography .117
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IWA 15:2015(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
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electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
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The committee responsible for this document is ISO/TMBG, Technical Management Board Groups.
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International Workshop Agreement IWA 15:2015(E)
Specification and method for the determination of
performance of automated liquid handling systems
1 Scope
This International Workshop Agreement (IWA) specifies methods for testing the volumetric
performance of air-displacement, system-liquid filled and positive displacement automated liquid
handling systems (ALHS), including an estimation of measurement uncertainties and established
traceability to reference standards (preferably, traceability to SI Units). The testing methods specified
in this document may also be used to measure the volumetric performance of automated liquid delivery
systems which do not aspirate the test liquid.
This IWA also specifies statistical methods for the determination of random and systematic errors
(including intra-plate and inter-plate comparisons), analysis of measured results when using
multichannel dispensing heads, and analysis depending on dispense patterns. It further defines terms
and formulae to be used for summarizing test results.
This IWA also specifies the information to be provided to users of ALHS, including the display of
summary results and performance claims.
This IWA is applicable to all ALHS with complete, installed liquid handling devices, including tips and
other essential parts needed for delivering a specified volume, which perform liquid handling tasks
without human intervention into microplates. Manipulation of the microplates on the deck of the
automated liquid handling system may be achieved automatically, semi-automatically, or manually.
This IWA addresses the needs of:
— suppliers of ALHS, as a basis for quality control including, where appropriate, the issuance of
supplier’s declarations;
— test houses and other bodies, as a basis for independent certification and calibration;
— users of the equipment, to enable calibration, verification, validation, and routine testing of trueness
and precision.
The tests established in this IWA should be carried out by trained personnel.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories
3 Terms and definitions
For purposes of this document, the following terms and definitions apply.
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IWA 15:2015(E)
3.1 Definitions
3.1.1
accuracy
closeness of agreement between a delivered volume and the
target volume
Note 1 to entry: The concept ‘accuracy’ is not a quantity and is not given a numerical quantity value. A liquid
delivery is said to be more accurate when it is accomplished with a smaller liquid handling error.
[SOURCE: ISO/IEC Guide 99:2007, 2.13, modified]
3.1.2
air displacement
liquid handling principle in which a body of air is contained between the piston and the test liquid
Note 1 to entry: It is possible to have a large air gap (piston systems), or smaller air gap between the test liquid
and the system liquid (liquid filled systems).
3.1.3
ALHS uncertainty
non-negative parameter characterizing the dispersion of the measured volumes relative to the
target volume
Note 1 to entry: Uncertainty is inversely related to accuracy, and is a quantity value. This value should be
expressed in accordance with ISO/IEC Guide 98-3.
[SOURCE: ISO/IEC Guide 99:2007, 2.26, modified]
3.1.4
aliquot
single delivery during a multi-dispense
3.1.5
automated liquid handling system
ALHS
system with a complete, installed liquid handling device, including tips and other essential parts needed
for delivering a specified volume without human intervention into microplates
Note 1 to entry: Examples of automated liquid handling systems include automated pipetting systems (APS), and
automated dispensing systems (ADS).
3.1.6
calibration
operation that, under specified conditions, establishes a relation
between the target volume of the ALHS and the delivered volume
Note 1 to entry: A calibration may be expressed by a statement, a calibration curve or a calibration table. It may
include a correction, but correction or adjustment is not a required element of a calibration.
[SOURCE: ISO/IEC Guide 99:2007, 2.39, modified]
3.1.7
dead air volume
captive air volume
air gap
air volume between the lower part of the piston
and the surface of the aspirated liquid
Note 1 to entry: It is possible to have a large air gap (piston systems), or smaller air gap for liquid filled systems.
Sometimes called captive air volume.
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IWA 15:2015(E)
Note 2 to entry: Commonly, an air gap can be adjusted through ALHS system parameters, while the dead air
volume or captive air volume cannot be adjusted (see 4.2.1).
3.1.8
delivered volume
quantity delivered by a liquid handling system
Note 1 to entry: Delivered volume is a conceptual term and cannot be known with complete certainty due to
measurement error.
3.1.9
dispense height
height at which the test liquid is dispensed relative to a stated reference
3.1.10
dispensing system
system for delivering liquids from a pre-filled liquid reservoir
3.1.11
disposable tip
tip, which is attached once and after use, as defined by the manufacturer, detached and intended to be
discarded
Note 1 to entry: Disposable tips are usually made of plastic.
Note 2 to entry: Disposable tips are in contrast to fixed tips, which are described in 4.3.4.
3.1.12
dry contact dispensing
dispensing of liquid while tip is in contact with the dry target
3.1.13
factory acceptance testing
internal vendor testing to ensure ALHS performance to specifications
3.1.14
forward mode pipetting
direct mode pipetting
pipetting mode where the entire aspirated volume is delivered
3.1.15
immersion depth
depth of the tip below the liquid surface
Note 1 to entry: Immersion depth can be applied to both aspiration and dispensing (wet contact).
[SOURCE: Toolpoint Photometric Volume Check Procedure:2008, modified]
3.1.16
individually controlled channel
liquid handling channel that can be operated independently of other channels
3.1.17
labware
materials used in conjunction with liquid handling operations
Note 1 to entry: Labware includes disposable tips, reservoirs, receiving vessels, adapters and microplates.
3.1.18
maximum permissible error
upper or lower permitted extreme value for the deviation of the dispensed volume from the target volume
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IWA 15:2015(E)
3.1.19
maximum specified volume
largest volume for which the manufacturer offers specifications
Note 1 to entry: The maximum specified volume may vary depending on instrument configuration (e.g. disposable
tip size, syringe size).
3.1.20
measured volume
quantity reported by a volume measuring system
Note 1 to entry: In practice, all measurements contain some measurement error. The measured volume is a
quantity value and serves as an estimate of the delivered volume which is not known with complete certainty.
3.1.21
measurement method
measurement procedure
detailed description of a measurement according to one or more measurement principles
Note 1 to entry: The source document (ISO/IEC Guide 99) draws a distinction between ‘measurement method’ and
‘measurement procedure’ and that distinction is ignored here. In this IWA, the terms are used interchangeably.
Note 2 to entry: The measurement method descriptions in this IWA detail the steps needed to make a volume
measurement and calculate certain descriptive statistics. Additional details needed to operate the ALHS are
part of the ‘test process’ as defined in 3.1.43. In this IWA, the measurement method is one of the components of
a ‘test process.’
[SOURCE: ISO/IEC Guide 99:2007, 2.6, modified]
3.1.22
measurement uncertainty
non-negative parameter characterizing the dispersion of the measured volumes
relative to the delivered volume
Note 1 to entry: Uncertainty is inversely related to accuracy, and is a quantity value. This value should be
expressed in accordance with the ISO/IEC Guide 98-3.
[SOURCE: ISO/IEC Guide 99:2007, 2.26, modified]
3.1.23
metrological traceability
property of a measurement result whereby the result can be related to a reference through a
documented unbroken chain of calibrations, each contributing to the measurement uncertainty
Note 1 to entry: Additional information can be found in the notes to definition (ISO/IEC Guide 99:2007, 2.41) and
the related term ‘metrological traceability chain’ (ISO/IEC Guide 99:2007, 2.42).
[SOURCE: ISO/IEC Guide 99:2007, 2.41]
3.1.24
microplate
flat plate with an array of wells
[1-5]
Note 1 to entry: Some dimensions of microplates are defined in ANSI/SLAS standards.
3.1.25
minimum specified volume
smallest volume for which the manufacturer offers specifications
Note 1 to entry: The minimum specified volume may vary depending on instrument configuration.
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IWA 15:2015(E)
3.1.26
multichannel head
group of liquid handling channels operated in common
Note 1 to entry: Common arrangements of multichannel heads include 8, 96, 384, and 1536 channel heads. Other
arrangements are possible, e.g. 2 channel to 1536 channel configurations.
Note 2 to entry: Pipetting channels in a multichannel head may be controlled by a single, common drive, or each
channel may be controlled individually.
3.1.27
multi dispense
repeat dispense
sequential dispense
a collection of dispenses without intervening aspiration
Note 1 to entry: First dispense can be different, and is frequently wasted.
Note 2 to entry: Repeat dispenses usually dispense repeatedly the same volume, while sequential dispenses
usually dispense different volumes.
3.1.28
non-contact dispensing
contact-free dispensing
free-jet dispensing
dispensing of the liquid while tip is in air and without contacting the target or the liquid contained
in the target
3.1.29
outlier
member of a set of values which is inconsistent with the other members of that set
3.1.30
pipetting system
system for aspirating and dispensing a specified volume of liquid
[SOURCE: Toolpoint Gravimetric Volume Check Procedure:2008, modified]
3.1.31
positive displacement
direct displacement
liquid handling principle in which a mechanical actuator is in direct contact with the test liquid
3.1.32
precision
the closeness of agreement between the measured volume of independent
delivered volumes under stipulated conditions
Note 1 to entry: Precision is conceptual and not a quantity value.
Note 2 to entry: Measurement precision is usually expressed numerically by measures of random error, such as
standard deviation, variance, or coefficient of variation under the specified conditions of measurement.
Note 3 to entry: The ‘stipulated conditions’ can be, for example, repeatability conditions of measurement,
intermediate precision conditions of measurement, or reproducibility conditions of measurement (see
ISO 5725-1:1994).
[SOURCE: ISO 5725-1:1994, 3.12, modified]
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IWA 15:2015(E)
3.1.33
random error
component of liquid handling error that in replicate deliveries
varies in an unpredictable manner
[SOURCE: ISO/IEC Guide 99:2007, 2.19, modified]
3.1.34
reservoir
liquid container
vessel that contains the liquid
3.1.35
reverse mode pipetting
pipetting mode in which excess volume is aspirated and remains in the tip after delivery
3.1.36
single dispense
individual dispense
single dispense per aspiration
3.1.37
site acceptance testing
in-situ testing at the user’s site, typically part of the installation process
3.1.38
supplier’s declaration
document by which a supplier gives written assurance that an ALHS conforms to the requirements of
one or more commonly accepted industry standards
Note 1 to entry: This IWA can be referenced as an applicable industry standard.
3.1.39
systematic error
component of volumetric error that in replicate deliveries remains
constant or varies in a predictable manner
Note 1 to entry: Systematic error is estimated by calculating the average volume of a series of deliveries and
comparing it to the indicated volume of the automated liquid handling system. Frequently this result is expressed
as a percentage of the indicated volume.
[SOURCE: ISO/IEC Guide 99:2007, 2.17, modified]
3.1.40
system liquid
liquid used to transmit energy between a mechanical actuator and the test liquid
Note 1 to entry: System liquids can reduce or completely eliminate system dead air volume.
Note 2 to entry: System liquid is usually deionized water. For special applications organic solvents such as DMSO
or aqueous solutions such as saline (e.g. 0,9 % NaCl) can be used.
Note 3 to entry: System liquid can be used for flushing and rinsing tips to minimize cross contamination.
3.1.41
target volume
indicated volume
selected volume
volume which is intended to be delivered
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IWA 15:2015(E)
3.1.42
test liquid
liquid used for the volume measurement
Note 1 to entry: May be aqueous or other solvents. Aqueous test liquids can be pure water or contain other
compounds such as buffers, dyes or salts. The chemical composition of the test liquid can vary significantly
depending on method.
3.1.43
test process
detailed description of an ALHS testing procedure including
system operation and measurement method
Note 1 to entry: The test process includes all details needed to reproduce the test or interpret the results. The
measurement method is defined in 3.1.21, and is only a part of the test process.
3.1.44
test report
document reporting the result of the testing
Note 1 to entry: Details regarding information contained in test reports is specified in Clause 8.
3.1.45
test result
value of a characteristic obtained by carrying out a specified test method
Note 1 to entry: Test result is a broader concept than measured volume. The test result can be a single measured
volume, a set of measured volumes, or descriptive statistics such as the mean or standard deviation of multiple
measurements. The test method should specify what form the test results take.
[SOURCE: ISO 5725-1:1994, 3.2]
3.1.46
traceability
metrological traceability
property of a measurement result whereby the result can be related to a reference through a
documented unbroken chain of calibrations, each contributing to the measurement uncertainty
[SOURCE: ISO/IEC Guide 99:2007, 2.41]
3.1.47
trueness
closeness of agreement between the average volume delivered in a
large series of deliveries and the target volume
Note 1 to entry: Trueness is inversely related to systematic error, but is not related to random error.
[SOURCE: ISO/IEC Guide 99:2007, 2.14, modified]
3.1.48
validation
...
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