UNIT SEVEN

Automation in Clinical Chemistry

 Objectives
 Upon completion of this unit the student will be able to:

 Define terms related to automation

 Describe the component parts of automated analyzers

 Discuss principles of current automated systems

 Describe the first stages in setting up a new instrument

in the laboratory
 Initial set-up
 Calibration
 Outline

 Definition of automation

 Component parts of automated analyzers

 Principles of current automated systems

 Automation - mechanization of a procedure
 Turnaround time: time for a test result to be reported
once the laboratory receives the specimen.
 Spectrophotometer: measuring the light of specific
wavelength transmitted through the solution in a cuvette
to determine the concentration of an analyte.
 Calibration-to transform the instrument response
measurement to a predicted output.
 Random-Access - different tests for each patient on the
same instrument
 Standard: a pure solution with known concentration
 Primary - A pure solution verified by the reference
method
 Secondary - A pure solution verified by a highly
accurate method
 Calibrator - a substance or mixture dissolved in a matrix
used to calibrate an instrument
 QC samples - Similar in makeup to patient samples used
for verifying validity
Spectrophotometry as part of Automation
 Manual spectrophotometer is common
 Detection system for clinical chemistry tests
 Back-up technique when the automated system is
temporarily not performing well

 The principle behind automated analysis of many clinical

chemistry tests is also spectrophotometry
 Automated analyzers mechanize the chemical analysis
process
Automated Chemistry Analyzer Components
 Sample cup holder
 Sample pump and pipettor
 Reagent pump and pipettor
 Test cuvettes
 Mixer
 Incubator
 Detection system
 Spectrophotometer
 Other
 Read –out device
 Waste container 10
Principle of Current Automated Systems
 Basic spectrophotometric liquid clinical chemistry
 AMS Autolab, Human Humastar80, Vegasys
 Many others

 Electrochemistry: Ion Selective Electrodes

 AMS Autolab, HumaLyte

 Immunoassay
 Fluorometric or Fluorescent polarization
 Chemiluminescent, Nephelometric
 Sample Pipettor and Pump
 Probe or pipettor

 Wash solution

 Reagent Pump and Pipettor

 Reagent ratio volume pump

 Deliver reagent volume

accurately
 Sample Cuvettes in Automation

 Cuvettes: contains test reaction

 May be placed in instrument by tech

 May be built into the instrument and self-washing

 Optical cell for test solution

 Solution in cuvette absorbs some light and transmits

remaining light based on concentration of analyte/
product.
 Basic Instrument Components
(Spectrophotometric analyzer)

 Basic spectrophotometer detection system components

include:
 Light sources (UV and visible)

 Wavelength selector (monochromator)

 Sample containers (cuvettes)

 Detector

 Signal processor and readout

 Waste Container
 Waste fluid removed
 Safety considerations in treating biohazardous waste
and toxic chemicals
 Part of daily maintenance to empty and disinfect
waste container

Manual Spectrophotometer
Automated Chemistry
Analyzer
Advantage & Disadvantages of Manual Methods
 Disadvantages
 Slower turnaround time (TAT)
 Requires more hands-on Technologist time
 Less precision and accuracy in Quality Control
 Tests may be less sensitive
 Often require larger sample volumes
 Increased safety risk to Techs (biological and reagent)
 Advantages
 May be less expensive and easier to operate
 Less skilled manpower 20
Advantage and Disadvantages of Automated
Methods
 Advantages
 Quicker TAT
 Less handling of biological specimens by Techs
 Greater precision and accuracy in Quality Control
 Greater sensitivity
 Require smaller sample size
 Can run and report many more test results in shorter
period of time
 Disadvantages
 May be more expensive
 More spare parts need to be available
 Requires higher skilled technologists
 Semi-Automation versus Automation
Chemistry Analyzers
 In Semi-automation there are steps performed by the
technologist:
 prepares sample for testing
 loads sample cup onto analyzer
 manually inputs Patient ID and Test(s) Requested into
instrument via keyboard
 In full automation:
 specimens are placed directly on the analyzer
 Barcode reader inputs Patient ID and test request
 Most semi-automated and automated instruments are:
 *Random-Access Analyzers
 Can run 50 or more tests per hour
 Technologist has more time for other lab responsibilities
(walk- away)
 Reports from the instrument are printed in “ready to send
format” to the patient’s hospital chart or hand deliver to
patient or clinician

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How to Unpack an Instrument (The instrument
is here, now what should I do?)
 A new automated instrument has
just been received in the
laboratory.
 The technologist must now set up,
calibrate and validate the
instrument, comparing it to the
manual method.
Automation Analyzer Vendors or Engineers
 Your instrument vendor (engineer)
may help with the installation,
calibration and validation of your
new instrument
 Engineers (vendors) are an
important resource:
 Keep their contact information
taped to your instruments
 Initial Instrument Setup
 Pre-installation Steps
 Out-of-the box steps
 Establish a working procedure
 Pre-installation Requirements
 Check for the following items:
 Proper electrical wiring and voltage, and uninterrupted
power
 UPS surge protectors and /or stabilizers
 Generators should be available
 Temperature controlled
 Adequate distilled water supply
 Check for the following items:
 Proper waste disposal capability
 Adequate air circulation / flow around instrument
 Dust free environment (cover when not in use)
 Stable bench top
 Before Beginning the Instrument Validation
 Turn on the power
 Permit instrument to stabilise/equilibrate
 Let all components reach proper temperature
 Set in any parameters that may be required
 Ranges, Temperatures
 Initial Instrument Calibration
 Follow manufacturers recommendation for reagent and control
preparation
 Place calibrator(s) on instrument in proper order sequence
 Run prepared calibrator(s) on both automated and manual
methods
 3-5 standards are analyzed for analyte
 Absorbance is measured
 Absorbance versus concentration graph is plotted
 Linearity is determined
 Concentration curve is stored in analyzer
 QC samples verify concentration curve
 Calibration Curve

1.00
absorbance

0.80

0.60

0.40

0.20

0.00
0 20 40 60 80 100 120

concentration
 Ongoing Automation Analyzer Calibration
 Determine QC results by standard curve or factor
 If controls within stated value for analyzer and
methodology, then move to instrument validation
 Test calibration will be repeated
 When there is a new lot number of reagent or
 In accordance with manufacturer’s recommendations
 On more frequent basis as indicated by quality control
results
 Evaluation of a New Automation Method

1. Precision

2. Comparison

3. Linearity

4. Reference range

5. Interferences
 Establishing Reference Ranges
 Reference ranges should be established for manual and
automated methods
 Materials used
 20 healthy patient samples previously obtained are run
over a period of at least 3 consecutive days
 Calculation of Reference Ranges

 Calculate x and SD for the data points

 Use ± 2 standard deviations to determine the

reference range for the healthy patients
 Instrument Maintenance

 This should be done by the technologists who

have received prior training.
 It includes for example, systematic and routine
cleaning, simple adjustment or replacement of
instrument and equipment parts.
 Daily, Weekly, Monthly
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Daily and Planned Preventative Maintenance
 It is important to follow good practices in using the
automated clinical chemistry analyzer:
 Performing daily maintenance according to
manufacturer’s instructions
 Checking the photometric linearity and
 Checking the wavelength frequently
 Record your results
 Track changes and problems
 Occurrence logbook
 Example Daily Maintenance:
 Priming Reagent Pump Tubing
 Ensures that no air bubbles are present
 Ensures that reagent will reach reaction tube
 Temperature Calibration
 Ensures cuvette temperature is accurate and stable
 Especially important for enzyme assays
 Recording the results you obtain for spectrophotometric
evaluation and maintaining the records.
 *If you don’t record what you do…then you didn’t do
Implementation Plan of new Analyzers
 Implementation only after Method Evaluation**
 Establish a working procedure [Write SOP)]
 Establish the quality control system
 Establish reference ranges
 Healthy range, specific patient population studies
 Instruct laboratory personnel
 Introduce the method into routine use
 Monitor routine performance
 Instrument Maintenance
 Summary Review Questions
1. What are some important terms and definitions related to
automation in clinical chemistry?
2. List the main components of an automated Clinical
Chemistry Analyzer.
3. Classify advantages and disadvantages of manual
spectrophotometric analysis and automated analyzers.
4. What steps are necessary for installation of a new
automated analyzer?
5. Why is method evaluation needed for automated clinical
chemistry analysis?
6. Name some examples of daily maintenance.
7. Describe the steps of calibration.
 References
1. Kaplan, L, Pesce A. Clinical Chemistry,,2nd Ed., CV Mosby
Co., St Louis, 1989
2. http://teaching.shu.ac.uk/hwb/chemistry/tuto
rials/molspec/uvvisab3.htm
3. http://www.ibms.org/pdf/pdf_science/princip
les_spectrophotometry.pdf
4. THE BIOMEDICAL SCIENTIST; Principles of
Spectrophotometry, p 135-137. February 2005

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