1. Prepared By:
Mr. PARTH P.
M. Pharm, Sem –II
Q. A. Department-SJTPC
Guided By:
Mr. Jignesh S. Shah
Asst. Professor of Q. A. Department-SJTPC, Rajkot
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2. Contents
Benefits of Automation
Need for Automation
Objective of Automation
Classification of Automatic analyzers
Types of Automatic analysis technique
Automation approach in analysis
Basic Automatic Analysis System
Automated Method in P’Copoeia
Good Automated Laboratory Practices
2
3. .
“One machine can do the work of fifty
ordinary men, no machine can do the work
of one extraordinary man”
Complete automation will lead to human
prohibition in pharma industries.
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4. Definition
IUPAC define automation as ‘the use of combinations of mechanical
and instrumental devices to replace, refine, extend or supplement
human effort and facilities in the performance of a given process, in
which at least one major operation is controlled without human
intervention, by a feedback mechanism’.
Mechanization, on the other hand, is defined as ‘the use of
mechanical devices to replace, refine, extend or supplement human
effort’. The distinction between the two terms is quite clear
according to IUPAC ,insofar as ‘automation’ describes systems that
involve a feedback loop
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5. Human Accuracy & precision Cost cutting
prohibition
Too large number of sample Increasing number of analyte
Advance
automation in
microchip , and
Complex statistical calculation Strict regulation microprocessor5
6. Benefits of Automation
Faster analyses up to 120 samples per hour
Up to 300 samples can be analyzed in batch
Automatic data recording and preparation
Being a closed system, automation reduces contamination, for e.g.,
from atmospheric gases
Greater accuracy and reproducibility of results as all samples are
subject to same processes
Smaller sample and reagent volumes which reduces cost
Automatic range changing, drift control and automatic sample
preparation 6
7. Need for automation.
The partial or complete replacement of human participation in
laboratory process is a growing trend
Increasingly stricter control of growing number of samples in
which a large number of analyts are to be determined at
increasingly low concentration
Cost reduction
In research for increased accuracy, precision, and productivity,
the pharmaceutical analyst seeks to select optimal measurement
and to automate as appropriate
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8. Automated device
They are defined as those encasing automation.
They are conceived to make decisions with the aid of feedback
system, without human intervention.
There is a different operation sequence for each situation
(sample).Some system are self-monitoring and self-adjusting ,have
greater independence than automatic devices and are sometimes
called ‘completely automatic’.
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9. Objective of Automation
Automation is used for:-
Facilitating an analytical technique or method
Processing of large number of samples
Determination of several components in the same sample
Reduction of human participation to
Avoid error
Cut costs
Increasing sample throughput
Process (industrial or otherwise ) control
Lowering consumption of sample and/or reagent(s)
Samples, occasionally dealt with in large number or valuable to
deal with manually
Analyts, which are sometime present in very dissimilar or low
concentration in sample.
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10. .
Reagents, some of which are rare or expensive even unstable.
Rapidity, frequently essential in large laboratories such as those in
hospitals, urgently requiring the analytical result, and of industrial
and other laboratories require in constant availability of data for
process controls.
Economy, in personnel and material expenditure.
Precision, closely related to the elimination of both definite and
indefinite errors arising from the so-called ‘human factor’ (tiredness,
mood, prejudice, pathological, complaints and so forth)
Data generation , some analytical technique are based on the
acquisition of a large number do data, especially in the drug
discovery and development stages.
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11. Classification of automatic analyzers:
According to the degree of automation
Automatic
semi-automatic
According to the way in which samples and reagents are
transported
Batch (discrete)
Continuous
Segmented
Unsegmented
Robotics
According to the number of analytes per sample
One parameter
Multi-parameter
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12. According to flexibility
Specific
Flexible
According to source
Commercial
Hand-made
According to the state of aggregation of sample
Gas analyzer
Liquid analyzer
Solid analyzer
According to sample frequency
One-off
Periodic
Continuous 12
13. Types of Automatic Analysis
Technique
Basically there are two types of automatic analysis
techniques/instruments:-
Discrete sampling instrument- In discrete sampling, each sample
undergoes reaction and measurement in a separate cuvet or chamber.
These samples may be analyzed sequentially or in parallel.
Continuous –flow sampling instrument- In continuous flow
sampling, the samples flow sequentially and continuously in tube
perhaps being separated by air bubble. They are each sequentially
mixed with reagent in the same tube at the sample point down stream
and then flow sequentially into a detector
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14. A. Continuous Flow Analysis
There are two kind of Continuous Flow Analysis:
i. Segmented flow analysis
It includes a peristaltic pump that continuously aspirates sample and
reagent, a variable no. of tubes constituting a manifold to circulate
liquid and a detector system.
Aspirated sample are segmented by injecting air bubbles that should
be remove before they can be reaching to the detector.
At detector air bubble are removed and thus each sample is separated
by washing solution, thus a square shaped detector response is
obtained, the height of rectangle is directly proportional to conc. of
analyte.
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15. .
ii. Flow Injection Analysis
FIA is like a HPLC without a column. It is low pressure and
without separation. The injected sample mixes and reacts with the
flowing stream. A transient signal is recorded.
FIA is based on the injection of a liquid sample into a moving
continuous nonsegmented carrier stream of a suitable liquid. The
injected sample forms a zone which is then transported towards a
detector. Mixing with reagent in the flowing stream mainly occurs
by diffusion-controlled process and a chemical reaction occurs.
Detectors continuously record the physical parameter as it changes
as a result of passage of sample material through flow cell.
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17. .
There are mainly five types Flow Injection Analysis:
i. Syringe based injection system
ii. Injection with rotary valve
iii. Proportional injection
iv. Merged injection
v. Hydrodynamic injection
Comparison of peaks of SFA and FIA
SFA peak FIA peak
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18. B. Discrete Analyzers ( Batch Analyzer)
A discrete analyzer handles each individual sample as a separate
entity and is usually a single channel instrument.
In some designs both sample and reagent are metered into discrete
reaction vessels.
However , most of the system have specially design cells that already
contain pre pack amount of required reagent for given analyte and
thus making sample introduction only the necessary step.
In both cases reagents are combine with sample in discrete cuvettes
where mixing, incubation and final color measurement occurs.
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19. Automation Approach in Analysis:
1. A serial (or sequential ) automation process
2. A parallel automation process
3. Hybrid Automation Systems
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20. 1.A Serial (Sequential) Automation
Process
The general characteristic of a serial automation process is
that a given determination reaches completion before the
next determination begins, although with some serial
automation systems, the second determination may be
started before the first is completed.
Serial automation could also be configured in an on-line
arrangement, where tandem processes in the chemical
determination are performed by collection from a flowing
stream.
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21. 2.Parallel Automation Process
Parallel Automation Process for chemical analysis is, simply, a
process where more than one automated chemical
manipulation is performed simultaneously.
These parallel manipulations can encompass some or all of the
following discrete analytical chemistry operations:
Experiment initiation,
Sampling (obtaining the samples),
Sample preparation,
Component separation,
Analyts detection and
reduction/reporting
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22. Such an on-line system could be used to
acquire a sample,
process it, and
perform the associated chemical measurement step
E.g.. in the case of
on- line micro dialysis/LC/MS or
on-line solid-phase extraction/LC/MS/MS
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23. 3. Hybrid Automation Systems
Hybrid automation systems for chemical analysis combine features
of both serial and parallel systems.
Some processes are conducted in serial, some are conducted in
parallel, and all are integrated into a single system
Tomtec Quadra-96 liquid handling
workstation.
Conceptualized semi automated 96-well liquid–liquid extraction
procedure.
Zymark combinatorial chemistry workstation
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24. Hybrid Automation = Serial Automation + Parallel
Automation.
Hybrid Automation Systems
In Robotic solid-phase extraction method development system,
a central robotic arm (XP) which service various arm peripherals,
and a 144-port vacuum manifold, used for solid-phase extraction
method development.
The system and development of the solid-phase extraction
columns, which are in parallel. Although a fully parallel system
would have been desirable, it was beyond the capabilities of
commercially available system at this time.
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25. Basic Automatic Analysis System
Sampling unit
Proportioning pump
Manifolds
Dialyzers
Constant temperature bath
Detector
Recorder
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27. Sampling unit:
The sampling unit enables an operator to introduce unmeasured sample
and standards into auto analysis system.
The unit in its earlier form consisted of a circular turntable.
The sample plate carrying these cups rotates at a predetermined speed.
The movement of turntable is synchronized with the movements of
sampling crook.
The crook carries a thin flexible polythene tube, which can dip into cup
and allow water, standard or test solution to be aspirated.
The samplers are fitted with a sample mixer, which enables the sample
to be mixed before and during aspiration.
The automatic samplers employs a different washing action between
samples.
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28. Proportioning Pump:
.
The function of proportioning pump is to continuously and
simultaneously push the fluids, air and gases through the analytical
chain.
Samples and reagents are driven single peristaltic pump.
A series of flexible plastic tubes, one from the sampler the other
from reagent bottles or simply drawing air, are placed length wise
along the platen spring loaded platform.
The roller head assembly is driven by a constant speed gear motor.
When the rollers are pressed down and the motor switched on, they
compress the tube containing liquid streams against the platen.
As the roller advance across the platen, they drive the liquid before
them.
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29. Manifolds:
A manifold mainly consists of a platter, pump tubes, coils, transmission
tubing, fittings and connections.
Mixing coils are used to mix the sample/reagent.
As the mixture through a coil, the air bubble along with the rise and
fall moton produces a completely homogenous mixture.
Delay coils are employed when a specimen must be delayed for a
completion of chemical reaction before reaching the colorimeter.
Various types of fittings are employed to join stream of liquids to split
a stream or to introduce a air segmentation to the stream.
The reagents line are segmented by introducing air through one or
more additional tubes in the manifold.
This produces a series of bubbles at a regular intervals in the liquid
stream. This is designated as bubble pattern
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30. Dialyzer:
.
Dialysis is accomplished to remove protein cells to obtain an
interference free analysis.
The dialyzer module consists of a pair of Perspex plates, the mating
surface of which are mirror grooved in a continuous channel, which
goes in towards the centre on itself and returns to the outside.
A semi permeable cellophane membrane is clamped between the two
plates. Cellophane membrane use has a pore size of 40-60Å.
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31. Constant temperature bath:
On leaving the dialyzer, the stream may be combined by one or more
additional reagents. It is then passed to a heating bath. A
thermostatically controlled immersion heater maintains a constant
temperature within ±0.1.
Detector system:- Mainly used detector
Colorimeter
Flame photo meter
Flourimeter
Signal Processing and Data-Handling:
Modern automatic analysis systems make use of a PC as multi tasking
data processor and system controller. However such multi tasking is
used with the use of microprocessor based analogue interface card
which fits neatly into a standard extension slot inside the computer.
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32. Recorder:
.
The most common type of recorder used with automated system is dc
voltage null-balance potentiometer recorder.
Significant fluctuations in the flow pattern may result in irregularities
of the base line on a recorder.
Irregularities are also produced due to a drift in the electronic circuit.
Pulse suppressor are used to smoothen out fluctuations.
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33. Automated Method in P’Copoeia
Automated method have been found especially useful in testing the
content uniformity of tablets and capsules and in facilitating methods
requiring precisely controlled experimental conditions.
In addition,the detection system and calculation of results for
automated methods are often computerized.
Before, an automated method for testing an article is adopted as an
alternative, it is advisable to ascertain that the results obtained by this
system are equivalent in accuracy and precision to those obtained by
the prescribed p’copoeial method.
Because of their versatility, this system designed for rapid
determination of specified substance often can be readily modified
by the addition of suitable modules and accessories to permit the
determination of one or more additional substance in dosage form.
e.g.in the automated analysis of articles containing both estrogen &
progestogens. 33
34. Good Automated Laboratory
Practices
The foundation of GALP standards comprises six principles inherent in the
EPA’s GLP requirements and its data management policies.
1. The system must provide a method of assuring the integrity of all entered
data.
2. The formulas and decision algorithms employed by the system must be
accurate and appropriate.
3. An audit trail must track data entry and modification to the responsible
individual.
4. A consistent and appropriate change control procedure must be capable of
tracking the system operation and application software.
5. Appropriate user procedure must be followed.
6. Alternative plans for the system failure, disaster recovery and unauthorized
access must be developed.
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35. FEATURES AND ADVANTAGES
OF AUTOMATION SYSTEMS
Speed.
Complexity.
Hardware.
Redundancy of hardware
Software.
Expandability.
Unattended operation.
Error recovery.
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36. Summary
Due to the ongoing demand for speed in industrial chemical
analysis, parallel automation processes are beginning to replace
serial automation processes, especially in those areas where high
numbers of assays or samples are expected.
For in situ or on-line situations where sparse strategic sampling is
the norm, serial automation will likely play a continued role.
Expensive robotic arms, while powerful and flexible, do not directly
lend themselves to parallel automation systems unless the effort is
made to combine them with specialized multichannel hardware. Such
hybrid systems are powerful and useful but are extremely
complicated to implement and maintain.
In the future, it seems likely that automated systems will be
miniaturized and that this miniaturized format will lend itself readily
to increased use of automation.
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37. Reference
Norbert R,Kuzel,Harold E,Roudebush & Charles E.S,
(1969),”Automation techniques in pharmaceutical
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406.
Edward H.Kerns,Li DI,(2005) “Automation in pharmaceutical
profiling” ,Chemical and Screening Science, Wyeth
Research,Princeton,NJ,114-123.
Berridge J.C,(1990), “Advance in automation of
pharmaceutical analysis”, Analytical chemistry department,
Pfizer central research,vol.7,No.12.pp.1313-1321.
David G.C, Thoru Sugawara, “Laboratory Automation in
Chemical Industries”,Marcel Dekker
Sugawara,T.,Cork,D.G.LaboratoryRoboticsandAutomation8:2
21–230,1996.
Skoog, D. A., West, D. M., and Holler, F. J. Fundamentals of
Analytical Chemistry, 7th ed., Saunders College Publishing,
37
Philadelphia, 1996.
