Hjelm et al Clinical equipment for primary health care in developing countriesIIIIIIIIIIIII III i’’ .i ,I |11 .11111 .11 III1.111111 I!1 II III1.1111 I_1111 IIII IIIII

introduced. It might even be necessary to develop a type ofmobile laboratory especially designed for use in developingcountries, in which all basic laboratory tests could be carriedout. This need not be more complex than a simple benchsupplied complete with all necessary equipment.

The experience gathered during the development of thePotLab and MonA concepts should be useful for this typeof project.

parties and similar meetings should be organised on acontinuing basis.

ACKNOWLEDGMENTSDuring the development of this project, many people world-wide,too numerous to mention, have helped with advice, hospitality,evaluation work, etc. Their collaboration is gratefully acknowledged.

General conditionsThere was general agreement that the PotLab and MonAconcepts fulfilled most specifications for photometers to beused at lower levels in the primary health care of develop-ing countries.

It was recommended that WHO should take an active partin the implementation of PotLab and MonA concepts by:(a) supplying information on the suitability of equipmertfor developing countries especially to organisations con-cerned with such supplies, e.g. UNICEF;(b) supporting the development of suitable analyticalprocedures;(c) involving international professional organisat.ions, e.g.International Federation of Clinical Chemistry (IFCC),International Committee for Standardization in Haemat-ology (ICSH), and the International Union of ImmunologicalSocieties (IUIS), in the development of methods and trainingprogrammes.(d) seeking involvement of the health care industry in boththe development aspects of projects and in overcoming theproblems that have so far limited availability of equipmentdesigned specifically for developing countries.

It was recommended that WHO should take steps toproduce specifications for a general clinical laboratorysystem, dedicated to the lower levels of primary health carein developing countries, because of the expected importancesuch a system would have for the screening and treatment ofcommon disorders.

All participants agreed that the meeting had been avaluable forum for the exchange of ideas between.interested.

REFERENCES[1] Clinical chemistry for developing countries. Report of the

joint International Federation of Clinical Chemistry andWorld Health Organization Meeting, September 20-24 1971,Geneva, Switzerland.

[2] Mitchell, F.L. The indigenisation of pathology. Annals ofClinical Biochemistry, 1975, 12, 45.

[3] Mitchell, F.L. Simplified instrumentation for the clinicallaboratory. Bulletin ofPan American Health Organisation,1976, 10, 212.

[4] Bull, G.M., Mitchell, F.L. The provision of clinical laboratoryservices in developing countries. Tropical Doctor, 1978,8, 104.

[5] Brown, S.S. A British approach to technology for rural care:’appropriate’ clinical laboratory systems. CS10 Communic-ations (1979), in press.

[6] Rideout, J.M. The Journal of Automatic Chemistry, 1979,1,(4), 223.

[7] WHO Consultation on Standardization in Haematology,Bilthoven, April/May, 1975. Document LAB/75.3.

[8] WHO Consultation on Standardization in Clinical Chemistry,Geneva, February 1975. Document LAB/75.2.

[9 Pocock, S.N., Rideout, J.M. The Journal ofAutomaticChemistry, 1979, 1(4) 222.

[10] Hjelm, M, The use of ’push the button’ analysers in clinicalchemistry. Organisation des Laboratoires-Biologie Prospect-ive. IIIe Collogue de Pont-a-Mousson, 1975. L’expansionScientifique Francaise, p.11.

[11] Wilding, P. and Kennedy, J.H. Manual of Routine Methodsin Clinical Chemistry for use in intermediate laboratories.1978, WHO LAB/78.1.

A total systems approach tolaborato ry automationPeter B. StockwellLaboratory of The Government Chemist, Stamford Street, London SE1 9NQ, U.K.

The concept of laboratory automation is a subject of muchconfusion. One of the major reasons for this is that there isno common understanding of the terminology itself as asubject except in a clinical sense. For example in the latestedition of Kirk-Othmer: Encyclopedia of Chemical Techno-logy 1] no direct reference to automated analysis is made;it includes only a reference to biomedical automatic analysers,thus neglecting a wide area of the use of automated analyses.The International Union of Pure and Applied Chemical(IUPAC) definition of automation clearly excludes mostsystems commonly marketed as automatic. It states "auto-mation is the use of combinations of mechanical devices toreplace, refine, extend or supplement human effort andfacilities in the performance of a given process, in which atleast one major operation is controlled, without humanintervention, by a feedback system". Almost all develop-ments described as automatic are classified within the IUPACdefinition of mechanisation; this states "mechanisation is theuse of mechanical devices to replace, refine, extend or

supplement human effort". A more simple definition ofautomation which is widely accepted by workers in thefield is, "the use of any facility either electronic or mech-anical, which eliminates some aspect of manual interactionand improves the efficiency of the analytical process". Inthis context, feedback mechanisms have little positiveadvantage to offer at present, although the use of micro-processor techniques clearly modifies this situation. Accordingto the definition which has been adopted for this paper,automation in laboratory analysis can be applied at any ofthe various stages throughout a procedure and attempts tominimise the level of routine operator intervention. Inaddition, it attempts to improve the level of quality controlby the use of mechanical, electronic and computer techniquesin a cost effective manner. Automatic analysis is furtherconfused, deliberately by commercial suppliers on occasions,by the automation aspects of an instrument purporting to befully automatic but referring to only part of the analyticalprocedure; most often, this is the measurement stage. A

2A6 The Journal of Automatic Chemistry

ANALYTICAL PROCEDURES

SAMPLEPREPARATION

MEASUREMENT

REPORT

Figure 1. Factors involved in analytical procedure.

Ill

Stockwell A total systems approach to laboratory automation

schematic representation of an analytical procedure as shownin Figure 1. Currie [2], defines the procedure as a systemsproblem and discusses the analytical process in some depth.The total systems approach to automation considers theanalytical problem in its widest sense, including interactionwith the customer both at the sampling and reporting stages.

In commercial chromatographic systems, the term auto-mation generally implies electronic or computer dataprocessing with, in some instances, the addition of injectionby a mechanical syringe. Such systems provide only limitedautomation. The calculation of peak areas is a time-consumingactivity but post-run calculations are often necessary.Injection of the sample through a syringe into a gas chroma-tographic column whilst being a skilled exercise occupiesonly a few seconds. In many situations the most time con-suming activity is the sample preparation and pretreatmentprior to sample .injection. In addition, the calculation ofpeak area is only the initial stage of any calculation routine.One commercial company has recognised this situation andan automated liquid chromatographic has been described byBurns [3].

Good automation to provide the most efficient use of aninstrumental system, relies on a proper and detailed speci-fication of the analytical requirements, followed by thesupport of a multidisciplinary activity to meet the specifi-cation as defined. A total systems approach implies consid-eration of the needs of all groups involved: the needs of thecustomer, the analyst, the laboratory manager and thelaboratory itself. For many reasons the full extent of theanalytical problems is not presented by the analyst in hisdiscussions with commercial suppliers or an in-house auto-mation group. For example, he may approach the auto-mation group and ask to be provided with an integrator tomeasure gas chromatographic peak areas, the analyticalrequirement eventually being to calculate the water in tardelivered from cigarettes using a gas chromatographic separa-tion and measurement. The analyst, who may in fact havelittle awareness of the scope of automation or the facilitiesoffered by available technology, presents ’how he sees theproblem being solved’ rather than setting out the real analy-tical needs. These two proposals present very different pro-blems. Since the analytical problem may not be a singleanalysis and may require the combination of a number ofanalytical measurements, the central coordination functionof an in-house computer system is important. This isexemplified by reference to the analytical and reportingprocedures required for the survey of commercial cigarettesto determine the ranking of the tar and nicotine contents.The analyst is concerned primarily with single analyticalresults but, in addition, the laboratory manager requires thestatistical mean moisture level .of a brand of cigarettesas one of the analytical parameters used in determining theaccepted ranking parameter, dry tar. This is obtained bysubtracting the moisture and associated nicotine level fromthe level of tar delivered.A total systems approach does not automatically result in

a fully computerised microprocessor controlled system ifthis is uneconomic. In some problems the most cost effectiveanswer is the introduction of mechanical dispensing andswitching systems controlled by simple cam timer 16gic. Asystem for testing dental materials and their resistance tosudden and prolonged temperature changes is an exampleof this approach [4]. In other situations, as a direct resultof the systems study, the analysis may remain in a manualregime but with the methodology changed significantly toimprove reliability and precision.

Specification of the problemThis is undoubtedly the most difficult part of designing andinstalling any automation scheme. For any new analyticalrequirement where automation is applied at the outset thismay not be such a serious problem as where automation is

Volume 1 No. 4 July 1979 217

Stockwell A total systems approach to laboratory automation

AutomaticChemistryGroup

AUTOMATION & COMPUTING SMOKING PRODUCTS

Section SectionHead Head

ComputerGroup

ElectronicsGroup

Instrument Applications InterfacingDesign Software

Preliminary Software Control ofResearch Development Experiments

Consultancy Computer ComputeTOperation Network

Economic& Scientific Statistics MicroprocessorAssessments Development

Research SmokeChemistry

Sub-Groupleader

Analysts

Sample Preparation& Analysts

Revenue

JOINT COMMITTMENT INVOLVEMENT AT ALL LEVELS

MUTUAL RESPECT, INTERACTION CONTINUAL

Figure 2. Various functions and inter-relationshipsbetween automation group and user group.

applied to procedures which have been undertaken manuallyfor many years. In the latter cases it may be very difficult todistinguish between the analytical needs and what the analystactually does manually. This is due to the analyst beingunaware of what is possible and economic in an automatedapproach. There are, no doubt, many ways of meeting.theobjective of defining a proper specification, but the approachtaken in this laboratory has been successfully applied to theautomation of a range of analytical problems. Whateverapproach is preferred, it is vitally important that the auto-mation group team or systems designer, whether in-house orprovided through a commercial organisation, must haste agood understanding of analytical chemistry.

The automation and computing group at the Laboratoryof the Government Chemist, was formed in 1969 with asmall team of analysts, each of whom had an interest inapplying automation to analytical problems. As the grouphas developed and expanded, the specialist skills, notably incomputer programming, electronics, statistics and mechanicalengineering have been incorporated into its functions.Particular care has been taken to retain the underlyingexpertise in analytical chemistry. In almost all projects orprogrammes the project leader of choice is a senior systemsdesigner with a good analytical background. More recently,the skills associated with microelectronics and microprocessorshave also been acquired. However, while the designer mustresist incorporating such novel devices in automated instru-mental systems where they are clearly superfluous, he mustbe aware of new technology and use it as a cost effectivesolution to the problem under consideration.

The customer, the analyst and the end user of the results(if this is not the originating customer) therefore have anextremely important role in any automation scheme.Without their full co-operation the success of the venturecan be seriously impaired. In addition to automated chemicalprocedures and sample handling techniques, the proposedscheme of automation may very well combine electronics,computing, and statistics through a sampling and qualitycontrol programme. The skill require to develop the necessaryautomation thus requires the formation of a multidisciplinaryteam which must interface with the users. Jointly, thedetailed specification must be defined and then developmentand implementation of the level of automation to meet thisspecification must proceed. Only when the groups concernedhave an effective dialogue with each other, are aware of the

constraints placed on each other and are totally committedto the value of automation, will the end result of the develop-ment be good automation. The resulting instrument willwork reliably in a routine situation and its usefulness couldbe clearly demonstrated. The various skills required in theautomation group are illustrated by reference to Figure 2,and have been discussed by Stockwell [5]. The approach toautomating the tobacco smoke analysis in this laboratoryserves to illustrate the total systems approach and its value,particularly to the staff in the tobacco section. Also shownin Figure 2 is the interaction between the two subdivisionsin the work programme. A sense of involvement, even on thepart of the most junior analyst and continual interactionbetween all members of the team must be encouraged fromthe specification stage through to the implementation ofthe automation developed.

Automation of the survey to determine the tar andnicotine levels in cigarettes available in the UKPublication of the report ’Smoking and Health Now’ by theRoyal College of Surgeons in 1971 [6] encouraged theDepartment of Health and Social Security in England tocommission the Laboratory of the Government Chemist toconduct a survey of all commercial cigarettes available onthe UK market. The object of this survey is to publish aleague table at six-monthly intervals which lists all brandsaccording to their tar and nicotine levels. The table wouldalso serve to advise the public of the relative health risksencountered by smoking cigarettes of different brands.

In the initial stages of the survey the level of automationwas restricted. The smoking and analytical protocols origin-ally adopted had to be similar to those in general use through-out the tobacco industry and these were basically manualprocedures. With the knowledge that the survey would be acontinuing requirement, the strategy adopted in the install-ation of an automated scheme took account of the longterm advantages of automating the analytical techniquesthemselves as well as the sample preparation and data pro-cessing aspects. The development of the automation schemefrom the initial survey, where only simple preparation anddata processing and reporting were automated, through to amore sophisticated online automated system as discussedhere, has been presented by Copeland and Stockwell [6].It is not intended in this paper to cover this ground againbut rather to use the example as an illustration of the various

218 The Journal of Automatic Chemistry

Stockwell A total systems approach to laboratory automation

Smoking machine

SE UP

Balance

Computer530

Gas-liquid Chromatograph

REPORT

Auto Analyser

Figure 3. Inter-relationship of automatic analyses linkedonline to central computer.

aspects of the total systems approach to automation.Because many of the automated devices have been intro-

duced whilst the survey work was in progress, it was veryimportant to prove their suitability for long term routineuse and, most importantly, to show that the results obtainedusing automation were statistically similar to those obtainedmanually. This is important in order to confirm that no biasis introduced by the transfer from the manual to the auto-matic regime,, examined. In practice, the relative ranking ofbrands must not be altered by transferring from a manual toan automatic system.

Since automation of the chemistry necessarily followedafter the implementation, of a sophisticated data processingand reporting structure, it is sensible that the computershould ultimately form a central co-ordinating and manage-ment function, that is act as a central registry of information.Discussions between the automation team and the user groupdefined a detailed specification for the requirements andeconomic assessments of the automation needs were carriedout jointly. Where an economic case existed automation wasintroduced. Where appropriate and when they exist commer-cial instruments were installed; where not, commercialsystems were modified in-house. Where commercial instru-ments were unavailable then automation was implementedusing instruments developed entirely within the Laboratory.The solutions proposed for individual analyses have not beenrestricted to any one of the many philosophies of automaticanalysis, and continuous flow or discrete analytical methodo-logies have been used as appropriate.

Table illustrates the various stages involved in theexperimental procedure. The first stage was to define thecustomer’s objective as stated above. Proper experimentaldesign ensures that the various measurements reportedshould be within the precision and accuracy required by thecustomers, the aim of these experiments being to report themean dry tar value with a precision on that mean of less than

+ 0.5 mg tar. As such, thirty measurements are made, each onfive cigarettes, over the six months of the survey. Samplecollection was an important facet because the values obtainedfor the measured analytes must be representative of thecigarettes actually available to the consumer. Collection atthe site of manufacture seemed to be the best solution.Sampling instructions are issued by the centralising computerto the collecting agency and gummed labels are printed toidentify and accompany the sample. These are transferredto the sample report forms. Samples of tar are generatedusing a conventional 20 channel automated smoking machine(Filtrona 300). This smokes each cigarette of the 5 sampleset in a controlled, defined manner agreed throughout theindustry. To ensure that day-to-day and inter channel varia-tions are minimised, a pseudo random smoking programmeis devised by the computer. Within each smoking programme(or run) so defined, a channel is allocated to analyse areference cigarette, to provide a quality control check. Thetar is then collected for each of the samples and retained on afilter pad prior to analysis. As a further quality control check,the puff count is measured; puff count is the total number of35ml puffs required to smoke the cigarettes to a definitepoint defined as the butt mark. More recently this parameterhas attained greater importance due to the requirement tomeasure carbon monoxide levels within the smoking proced-ures. This and other analytical parameters are illustrated inFigure 3 which shows all the measurements linked in anonline manner to the central computer. The weight .of tarproduced by the cigarattes is measured directly using anonline electronic balance. The dry tar value used for rankingpurposes is determined from this value by subtracting thewater and nicotine (defined as total alkaloids). The filterpads are extracted and an aliquot taken from water measure-ment using a gas chromatograph. The gas chromatographincorporates an automated injection system which is cottrol-led by the central computer. The computer also digitises the

Volume No. 4 July 1979 219

Stockwell A total systems approach to laboratory automation

analogue data, integrates the peak areas and carries out sub-sequent data reduction and reporting. The levels of totalalkaloids are measured using the continuous flow principleon a Technicon AutoAnalyzer using a cyanogen bromideprocedure.

The results for each batch of 20 analyses are then presentedto the analyst together with analytical calibration data. Thecombined analytical measurements are available to the sectionmanager who can relate these measurements to the data basefor each of the cigarette brands. The validity of each resultcan be compared with past data, to highlight changes incigarette specifications and analytical variations. Graphicaloutputs and histograms provide a valuable additional facilityavailable to the management. Cusum plots form an effectivemeans of evaluating this historical data and also of comparingdata with other contributing laboratories.

Once data have been validated they are incorporated intothe data base for the particular brand and used in the currentsurvey. Each monthly set of results and the accumulatedstatistical mean data are reported to the customer andexchanged with the industry. Finally, at the end of thesurvey a table, ranking the brands in ascending order of tarlevel (the League table), is prepared by the central computersystem in a format ready for publication to the generalpublic.

Figure 4 shows the various analytical processes and theprogramming format which achieves the levels of automation

so far described. The process of automation has evolvedsince the initial survey and, because of the close liaisonbetween the automation group and the tobacco section,it has been able to cope with the customer’s changingdemands. It is flexible enough to be further enhanced tomeet changing needs such as the addition of further analytemeasurements. Carbon monoxide has recently been includedin the survey parameters; however, these are not yet pub-lished in the UK. The scope of the survey has been changedand data can now be generated for Health Tax purposes andthe programmes can be extended to cover other surveyswhich may be undertaken on a contract basis in the. future.

The experience gained in operating this analytical schemehas been extremely useful for other aspects of work in theLaboratory. Contrary to popular belief which clearly expectsthat automation and computerisation, in particular, requirethe analyst to abdicate control to a machine, the schemedevised has provided the analyst with a considerable degreeof control over the procedures. It is necessary to accept theconstraints on the analyst, on the customer and on the systemdesigner, and there must be a willingness to work towardseconomic benefits and not exclusively towards scientificand technical interests.

Automation of the complete processes from the initialsampling including the various measurement stages throughto the final reporting has been clearly demonstrated. Thefinal product, the published league table of tar and nicotine

Labels

140 Brands runs

Samples 5 cycles

6 months 210 plans

Smoking plans

Sample selection

Propanol extraction

GLC with autoinjector

H2SO, extraction

File preparation

C.F.N. weighed

MACHINE SMOKING-Puff Counter

N.D.I.R.

AutoAnalyser using CNBr

Daily Report and error diagnostics

BRAND FILE

Brand code Factory No. of results

Access code Price Address

Brand name Inserts

Mnfr. Smoking Plans

Country

Surveys LOG

details

RESULTS FILELGC MFR

Age, Factory, Plan mods.

lmg

Average Puffs

coCO

T.P.M. calculated-

Water calculated

Nicotine calculated

P.M. (W.N.F.) calculated

(Labeller)

(Planner)

(Altar)

(RSUP)

(Altar)

Manipulate brand details

Print brand details

Sample costing=

Labels

Smoking plans

Print Log

Monthly housekeeping

Monthly print

Outlier check

Manipulate data

Final check

(RSUP) Multipart print

FULL RESULTS/TABLES/CUSUMS

Data distribution

Figure 4. Diagramatic representation of the relationshipbetween the automatic analytical instruments, the datafiles, and the large interactive control programmes.

220 The Journal of Automatic Chemistry

Stockwell A total systems approach to laboratory automation

LOW TARUndo4Under 4Under 4

88

Embassy Ultra Mild 0.3John Pby King Siz Ultra Mild Under 0.3SlkCut UIt Mild with Substitute Under0.3

temmK.S o.6PeerSlcial Extra MildKinSize(w,th Cyt) 0.6

8 PiccadillyMiM 0.58 SilkCut Kin8SLwithS 0.78 SlkCut No.3withSubstRu 0.79 BelairMenthol Kings 0.69 F.ndssyNo. ExtraMild 0.7s Embmyo.Stx 0.S

9 John Ptaym’KinSizwithNSM 0 7

9 PetStuyvesant Exb’a Mild KinSLt,e 0.89 No.6Extra Mild 0.79 SlkCut 0.99 SlkCut Intwnabon 0.99 SlkCutI(nSz 1.09 SlkCutNo.3 0.89 SlkCut No. S 0.810 ConsuMenth! 0.6

10 Consulate No.2 0.610 F.xbMild 0.810 Player’s No. 10with NSId 0.7

LOW TO MIDDLE TAR

12 B&H MiMwithStM#ute 1.112 Gautoises Filter Mild 0.712 Jhn PlayerCadtonPremium 1.113 Gauloises Longues 0.813 GitanesInt1Itmal 1.113 John PlayerCar#on LongSize 1.313 PlayeNo. 10 Extra Mild 0.813 St.Mori 0.914 BlackCat No.9 1.014 John PlayerCartton King Size 1.514 Kent 1.114 Peter Stu,)vesant KingSize 1.114 Philip Morns International 1.214 Piccadilly No.7 1.015 Benson&Hedm;.Mild 1.415 FilterTip 1.015 Chesterfield KirSize Irilter 1.315 [squeBleu O.815 GitanesCaporal Filter O.91,5 PeerSpecial Mild KinSize (with Cytrel) 1.1

Figure 5. End product of analyses- part of a posterillustrating the league table of the tar and nicotine levelsin cigarettes available on UK market.

Table 1. Illustration of tar and nicotine analyses problem andanalytical solution.

Sampling Duplicate gummed labels sent to samplingsite. These serve to identify sample through-out survey and are attached to sample packetand later test note.

2 Smoking programme Computer prepares sets of randomisedsmoking programmes. Each of which selectsthe appropriate band to be smoked on eachof the smoking machines twenty channels.Within each run a monitor cigarette is alsosmoked for quality control purposes.

3 Sample preparationand analysis

4 Analytical reporting

Filter pads are weighed prior to smokingand again once 5 cigarettes smoked and tarcollected. Analytical processes linked tocentral computer are shown in more detailin figure 3.

Calibration data and individual results areavailable to each analyst. Laboratorymanager has access to detailed brand results,is able to select data and or institute retestanalyses. Trend analysis via histograms andthe cusum facility also. provide qualitycontrol under direction of the tobaccosection manager. Files all protected by password entry system.

5 Statistical reporting Monthly trend results and six monthlyrolling average results with summary statis-tics data are available. Results made availablethrough DHSS to cooperating industrylaboratories.

6 Final reporting League table ranking brands in assendingorder of tar produced reading for publicttion.

levels is shown in Figure 5. In many laboratory situationsautomation to this extent may not be merited on economicgrounds, however it is valuable to consider even simpleanalytical problems in the manner described above. Improve-ments in methodology rather than automation may wellresult by the proper definition of the analytical requirementsand these in themselves may produce untold advantages.Consideration of the problems of data processing and com-puterisation outside the context of the complete problem,including the analytical procedure, may well result in expen-sive and inefficient levels of automation.

AcknowledgementsBecause of the complex nature of this automation programmeand the need for such detailed and close co-operation, manypeople, notably all the members of the automation team,have been associated with different facets of this work.Their skills and enthusiasm for automation and computingare gratefully acknowledged.

REFERENCES1] Encyclopedia of Chemical Technology, Kirk Othmer, Third

Edition, John Wiley and Sons, New York.[2] Currie, L.A., Treatise of Analytical Chemistry Part Vol

Third Edition, Editors Kolthoff, I.M., and Elving, P.J., Wiley,New York.

[3] Burns, D.A., Seventh Technicon International Congress, NewYork, 1976, Proceedings publ. 1977.

[4] Morley, F., and Stockwell, P.B., Journal of Dentistry, 1977,5, 39.

[5 Stockwell, P.B., Journal of Automatic Chemistry 1978, 1, 10.[6] Copeland, G.K.E., and Stockwell, P.B., Topics in Automatic

Chemistry Editors Stoekwell, P.B., and Foreman, J.K. publ0Horwood, Chichester, Sussex p. 265.

Volume No. 4 July 1979 221