AUTOMATION

DR.V.G.KARPAGHAVALLI
DEPT OF BIOCHEMISTRY
STANLEY MEDICAL COLLEGE
 OBJECTIVES
• Definitions
• Advantages
• History
• Basic concepts
• Steps involved in automation
 Automation
• Automation in clinical chemistry describes the process
where an analytical instrument perform many tests
with only minimal involvement of an analyst.

• The International Union of Pure and Applied Chemistry

(IUPAC) define automation as "The replacement of
human manipulative effort in the performance of a
given process by mechanical and instrumental devices
that are regulated by feedback of information so that
an apparatus is self-monitoring or self adjusting”.
 Advantages
• Handle larger workloads without comparable increases in
staff.
• Instrument performs a repetitive task by itself,
• allows the instrument to perform a variety of different tasks.
• Intelligent automation allow some individual instruments to
self-monitor and respond appropriately to changing
conditions.
• reduction in the errors of analysis through the elimination of
tasks that are repetitive .
• The improved reproducibility has led to a significant
improvement in the quality of laboratory tests.
• less time consumption per sample analysis,
• more number of tests done in less time,
 Evolution of automation
DATES SAMPLING PROCESSING REACTION COMPUTATION

1901-1950 H H H H

1950-1959 M H/M M H/M

1960-1969 M M M M/A

1970-1979 M M A A

1980 to M/A A A A
present

• H-HUMAN
• M- MECHANISATION
• A- AUTOMATION
 History
• 1956- first auto analyser Leonard Skeggs –Glucose,
urea, calcium
• Multichannel system 20 analytes-150samples/hr
• 1959- Robot Chemist discrete analysis
• 1968 -centrifugal analysers for discrete analysis
• 1970 –electronic automation and LIS
• 1980 random access analysers, discrete, STAT,
endpoint ,kinetic assay, photodiode array
• Dry chemistry analysis
• Integrated modular analysers
• Total lab automation
 Terminology
• Single channel analysis
• Multiple channel analysis
• Sequential analysis
• Batch analysis
• Discrete analysis
• Throughput
 Basic Concepts
• Automated analyzers generally incorporate
mechanized versions of basic manual
laboratory techniques and procedures.
• modern instrumentation is packaged in a wide
variety of configurations
• random-access analysis
– Analyses are performed on a collection of
specimens sequentially, with each specimen
analyzed for a different selection of tests.
 other configurations
• Continuous- Flow analyzers:-first automated
analyzers used in clinical laboratories.
– Single-channel analysis
– Multiple-channel analysis
• Centrifugal analyzers -use discrete pipetting
to load aliquots of specimens and reagents
sequentially into discrete chambers in a rotor,
with the specimens subsequently analyzed in
parallel .
 Unit Operations in an Analytical
Process
• Specimen identification
• Specimen delivery
• Specimen processing
• Sample introduction and internal transport
• Sample loading and aspiration
• Reagent handling and storage
• Reagent delivery
• Chemical reaction phase
• Measurement approaches
• Signal processing, data handling, and process control
 1-Specimen Identification
• the identifying link between patient and
specimen is noted at the patient’s bedside,
and maintained throughout
– 1) transport of the specimen to the laboratory,
– 2) subsequent specimen analysis, and
– 3) preparation of a report
 Bar code labeling
• The unique label is affixed to the specimen
collection container
• Code 39 is followed
• A bar coding system
• bar code is an array of rectangular bars and
spaces arranged in a predetermined pattern
• light beam from the scanner is absorbed by the
dark bars but reflected by the light spaces.
• light signal  electrical signal  digitized.
Code 39 allows both the patient’s name and id no in human and machine readable form
Advantages of using bar code labels
• Elimination of work lists for the system
• Avoidance of mistakes during placement of tubes
in the analyzer
• Analysis of specimens in random sequence.
• Avoidance of possible tube mix-up when serum
must be transferred to a secondary container.
• Decrease in identification errors.
– Automatic reading of bar code labels reduces the
error rate from 1 :300 characters (for human entry) to
about 1 : million
 RFID labels
• RFID labels can be encrypted to shield the
encoded data, ensuring that sensitive
information is kept confidential.
 2-Specimen Delivery
• Automated methods often used to deliver
specimens to the laboratory include:-
– pneumatic tube systems,
– electric track vehicles, and
– mobile robots.
 Pneumatic tube systems
• Rapid specimen transportation
and are reliable when installed
as point-to-point services.
 Mobile robots
• used successfully to transport
laboratory specimens both
within the laboratory and
outside the central
• Some mobile robots have
been integrated with robotic
systems that automate
loading and unloading of
specimens
• others initiate an audible or
visual signal on arrival at a
specified station
 Electric track vehicles
• Electric track vehicles have a larger carrying capacity than
pneumatic tube systems and do not have problems with
damaging specimens by acceleration and/or deceleration
forces.
• Some systems maintain the carrier in an upright position
• The containers can hold dry ice or refrigerated gel packs
with specimens if desired.
• Disadvantage
– cost of moving the track and loading/unloading stations
– staff may be necessary to unload the carts and transport the
specimens to their final destination
 3-Specimen Preparation
Conventional • Automation
• The clotting of blood in • Use of whole blood
specimen collection tubes, – For ISE
• their subsequent – Dry reagent films
centrifugation, and
• Automated preparation
• the transfer of serum to
– Special wheel 2 degree
secondary tubes
freedom X and Z
• If performed manually, the
process results in a delay • Use of robotics
in the preparation of a
specimen for analysis.
Basic configurations of robotic devices

CARTESIAN CYLINDRICAL ARTICULATING

4-Sample handling, transport and delivery
• In most situations the specimen for automatic
analysis is serum or plasma.
• Analyzers sample directly from primary collection
tubes or cups with aliquots from the original
specimen tubes
• Sample cups are designed to:-
– minimize dead volume,
– minimize evaporation,
– decrease thermolability,
– photodegradation
Sample loading zone may be
• (1) a revolving tray or turntable,
• (2) a mechanical belt, or
• (3) a rack or set of racks by which specimens are
delivered in a predetermined order to the sample
aspiration station of the analyzer.
Sample probe design
• The use of level sensors, which restrict the penetration
of sample probes into specimens and provide
smoother motion control, greatly reduces splatter.
• Developed closed-container sampling systems
– the specimen probe passes through a hollow needle that
initially penetrates the primary container’s rubber stopper.
Sample loading zone
 5-Specimen Processing
• Removal of Protein and Other Interferents
– (1) dialysis,
– (2) column chromatography, and
– (3) Filtration
• Separations in Immunoassay Systems
To separate free and bound antibodies , automated immunoassay
analyzers use bound antibodies or proteins in a solid-phase format.
– (1) beads,
– (2) coated tubes,
– (3) microtiter plates,
– (4) magnetic and nonmagnetic microparticles, and
– (5) fiber matrices.
Separations in Immunoassay Systems
 Sample transport and delivery
Continuous-flow systems, • In discrete analysis
(Random access analysis)

peristaltic pumps Positive–liquid displacement pipettes

Centrifugal analyzers
 6-Reagent Handling and Storage
• Ready to use liquid reagents
• Inventory is maintained by system -no of tests
• On board refrigerated storage for reagents
• Some analyzers use dry tablet reagents
• Others use reagent-impregnated slides or
strips.
• Still others rely entirely on electrodes to react
with specimens
 Reagent Identifcation
• Labels on reagent containers include
information such as
– (1)reagent identification,
– (2) volume of the contents or number of tests,
– (3) expiration date, and
– (4) lot number.
• Many reagent containers carry bar codes that
contain some or all of this information,
 advantages of reagent bar codes
• inventory management,
• ability to insert reagent containers in random
sequence, and
• ability to automatically dispense a particular volume
of liquid reagent.
• level sensing system on the reagent probe, alert the
operator
• In immunoassay systems, a bar code on a reagent
container contains key information about calibration
curve .
 Open Versus Closed Systems
• With an open analyzer, the operator is able to
use“in-house” reagents or reagents from a variety
of suppliers.
• Such analyzers usually have considerable flexibility
and are adapted readily to new methods and
analytes.
• A closed-system analyzer requires the reagent to
be provided by the manufacturer.
• Most immunoassay systems and point-of –care
applications are closed
 7-Reagent Delivery
• Liquid reagents are delivered to mixing and
reaction chambers by pumps or by positive
displacement syringe devices.
• For those analyzers in which more than one
reagent is acquired and dispensed by the
same syringe, washing or flushing of the probe
is essential to prevent reagent carry-over.
 8-Chemical Reaction Phase-

• continuous-flow system –

• In discrete analysis (Cuvette )

Reusable cuvettes needs laundry systems for Disposable on board manufactured

rinsing and drying cuvettes
 Mixing of Reactants
• In a discrete system, these include:
– 1. Forceful dispensing.
– 2. Magnetic stirring.
– 3. Vigorous lateral displacement.
– 4. A rotating paddle.
– 5. The use of ultrasonic energy.
• Continuous-flow analyzers- tumbling action of the stream
in a mixing coil.
• Dry reagent systems -the serum completely interacts with
the dry chemicals as it flows through the matrix of the
reaction unit.
Dry reagent systems
Timing of Reactions
• In discrete random-access analyzers, samples
and reagents are added to a cuvette in a timed
sequence, and detector signals are measured
at intervals to follow the course of each
reaction.
Thermal Regulation
• Devices used to control temperature include
– (1) air baths,
– (2) water baths, and
– (3) contact with warm plates.
 9-Measurement Approaches
Automated chemistry analyzers use a variety of optical
measurement devices including
– (1) photometers
– (2) spectrophotometers,
– (3) reflectance photometers,
– (4) fluorometers, and
– (5) luminometers.
Immunoassay systems use reaction schemes that produce
– (1) fluorescence,
– (2) chemiluminescence, and
– (3) electrochemiluminescence.
Ion-selective electrodes and other electrochemical
techniques
 Photometry/Spectrophotometry
• Measurement of absorbance requires the following three basic
components
• 1. An optical source – tungsten lamps, quartz-halogen lamps, deuterium
lamps,mercury lamps, xenon lamps, and lasers. 300 to 700 nm.
• 2. A means of spectral isolation-
– interference filters peak transmissions of 30% to 80% and bandwidths of 5 to 15
nm
– Monochromators with movable gratings and slits provide a continuous choice of
wavelengths.
– many manufacturers use a stationary, holographically ruled grating, coupled
with a stationary photodiode array, to isolate the spectrum
• 3. A detector.
– Photodiodes either as individual components or in multiples as an array.
– Photomultiplier tubes
• Proper alignment of cuvets with the light path(s) is important in both
 Reflectance Photometry
• The intensity of the reflected light from the
reagent carrier is compared with that reflected
from a reference surface
 Fluorometry
Fluorescence is the emission of electromagnetic
radiation by a species that has absorbed exciting
radiation from an outside source.
Turbidimetry and Nephelometry
to measure plasma proteins and to perform
therapeutic drug monitoring.
Chemiluminescence and Bioluminescence
excitation event is caused by a chemical or
electrochemical reaction
 Electrochemical methods
• The most widely used in ion-selective electrodes.
• These electrodes have replaced flame photometry
in the determination of sodium and potassium.
• The relationship between ion activity and the
concentration of ions in the specimens must be
established with calibrating solutions, and such
electrodes need to be recalibrated frequently to
compensate or alterations in electrode response.
 10-Signal Processing, Data Handling, and
Process Control
• Analog signals from detectors are converted to digital forms by analog
to-digital converters at a rate of 103 to 105 conversions per second.

• complex, nonlinear standard responses from nonisotopic immunoassays

and reflectance spectrometry are readily transformed into linear
calibration curve

• Autoverification -is the process whereby patient results generated from

interfaced instruments are compared by computer software against
laboratory-defined acceptance parameters.
– If results fall within these defined parameters, the results are
automatically released for reporting with no additional laboratory
staff intervention.
– Any data that fall outside the defined parameters are reviewed by
 Unit Operations in an Analytical
Process
• Specimen identification
• Specimen delivery
• Specimen processing
• Sample introduction and internal transport
• Sample loading and aspiration
• Reagent handling and storage
• Reagent delivery
• Chemical reaction phase
• Measurement approaches
• Signal processing, data handling, and process control
STAND ALONE AUTOANALYSER
INTEGRATED MODULE CHEMISTRY , ISE AND IMMUNOASSAY
 TOTAL AUTOMATION FOR THE
CLINICAL LABORATORY
• Significant progress has been made in
automating preanalytical and postanalytical
activities and integrating these operations
with analytical systems.
 Automated Specimen Processing
• receiving the specimen,
• inspecting it for appropriateness (labeling, container
type, temperature, and quantity of specimen),
• logging onto the LIS,
• labeling the specimen with an accession number, and
• separating urgent and stat specimens from routine
specimens.
• sort for centrifugation and aliquoted
• sort into instrument-specific racks for analyzers.
 TOTAL LAB AUTOMATION
• conveyor transport the specimens are moved to various
workstations,
• interfacing to automated analyzers,
• more sophisticated process control, and,
• a specimen storage and retrieval system.
• Some systems use an open design, which permits
interfaces to analyzers from a variety of vendors, whereas
other systems are of a closed design and are interfaced
only to the vendor’s own or a limited number of
analyzers.
Conveyor Belts- main feature of integrated or so-
called total laboratory automation systems

Loop conveyor

a unidirectional conveyor
 Laboratory Automation System (LAS)

• Also called middleware

• Is the control software that read specimen’s bar code
and obtain information from the laboratory’s LIS
about specimen type and ordered tests.
– calculate the number of aliquots and the proper volume for
each depending on the tests requested,
– route the specimens to analyzers,
– recap the specimens,
– retain the specimens for repeat, reflex, and dilution testing.
– autoverification of the test results
– linked with HMIS and results released along with
demographic details of patient and doctor’s name
 PRACTICAL CONSIDERATIONS
Automation of a part or all operations
Evaluation of Requirements:
• Evaluation begins with mapping of the current
laboratory work-flow from the arrival of patient
specimens through completion of testing and reporting
of results.
• Determining process steps that
– (1) are bottlenecks,
– (2) waste labor, and
– (3) are prone to error
 Other areas
Urine analyzers
• It is more difficult, because of the broad range of
concentrations of many urine constituents
• This requires a low limit of detection to measure
low concentrations and
• expanded linearity to permit measurements of high
concentrations without dilution.
• However, with new-generation analyzers,
automation of urinalysis is gaining acceptance
 Cell Counters
complete blood count (CBC) have been
automated through the use of
• the “Coulter principle,” which is based on cell
conductivity,
• light scatter, and
• flow cytometry.
 To conclude
• The history of automation in the clinical laboratory is long and
varied.
• Manual testing is clearly of the past century for a modern
laboratory except for a few very specialised tests.
• modern automated methods have become inevitable
especially to avoid the inherent variability of manual
procedures.
• The challenge is for laboratories to embrace the right kind of
automation to best meet their specific patient testing needs
• There are myriad options available, from stand-alone
integrated systems, to pre- and post-analytical modules that
can be mixed and matched with analytical units, to total
laboratory automation. This is definitely a situation in which
Thank you
 References

1. James C. Boyd, and Charles D. Hawker, chapter 19, Automation in the

Clinical Laboratory, Tietz Textbook Of Clinical Chemistry And Molecular
Diagnostics 5th ed(2012),469-485.
2. David A Armbruster, David R Overcash, Jaime Reyes, Clinical Chemistry
Laboratory Automation in the 21st Century - Amat Victoria curam (Victory
loves careful preparation) Clin Biochem Rev 35 (3) 2014:143-153
3. Bakan Ebubekir, Ozturk Nurinnisa and Kilic-Baygutalp Nurcan* Automation
in the clinical laboratory: integration of several analytical
andintralaboratory pre- and post-analytical Systems ,Turk J Biochem 2017;
42(1): 1–13