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18 ANALYTICAL METHODS, AUTOMATED

such hybrid devices. Such devices will be available in the market in the near future.

BIBLIOGRAPHY

Cited References

1.Holter NJ. New method for heart studies: Continuous electrocardiography of active subjects over long periods is now practical. Science 1961;134:1214–1220.

2.Heilbron EL. Advances in modern electrocardiographic equipment for long-term ambulatory monitoring. Card Electrophysiol Rev 2002;6(3):185–189.

3.Kadish AH, et al. ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography: a report of the ACC/AHA/ACPASIM task force on clinical competence. Circulation 2001;104:3169–3178.

4.Kinlay S, et al. Event recorders yield more diagnoses and are more cost-effective than 48 hour Holter monitoring in patients with palpitations. Ann Intern Med 1996;124:16–20.

5.Hinman AT, Engel BT, Bickford AF. Portable blood pressure recorder accuracy and preliminary use in evaluation intradaily variations in pressure. Am Heart J 1962;63:663–668.

6.Zachariah PK, et al. Blood pressure load: A better determinant of hypertension. Mayo Clin Proc 1998;63:1085–1091.

7.White WB, Dey HM, Schulman P. Assessment of the daily blood pressure load as a determinant of cardiac function in patients with mild-to-moderate hypertension. Am Heart J 1989;118:782–795.

8.Pickering TG. The clinical significance of diurnal blood pressure variations: dippers andnondippers. Circulation1990;81:700–702.

9.Verdecchia P, et al. White-coat hypertension: not guilty when correctly defined. Blood Press Monit 1998;3:147–152.

10.Pickering TG, et al. How common is white coat hypertension. Hypertension 1988;259:225–228.

11.Palatini P, et al. Target-organ damage in stage-1 hypertensive subjects with white coat and sustained hypertension: results from the HARVEST study. Hypertension 1998;31:57–63.

12.Brown MA, Buddle ML, Martin A. Is resistant hypertension really resistant ? Am J Hypertens 2001;14:1263–1269.

13.Myers MG, Haynes RB, Rabkin SW. Canadian hypertension society quidelines for ambulatory blood pressure monitoring. Am J Hypertens 1999;12:319–331.

14.Pickering T. for the American Society of Hypertension ad-hoc Panel. Recommendations for the use of home (self) and ambulatory blood pressure monitoring. Am J Hypertens 1996;9:1–11.

15.O’Brien E, et al. Use and interpretation of ambulatory blood pressure monitoring: recommendations of the British Hypertension Society. BMJ 2000;320:1128–1134.

16.Halligan A, et al. Twenty-four-hour ambulatory blood pressure measurement in a primigravid population. J Hypertens 1993;11:869–873.

17.Conway J, et al. The use of ambulatory blood pressure monitoring to improve the accuracy and reduce the numbers of subjects in the clinical trials of antihypertensive agents. J Clin Exper Hypertension 1986;8:1247–1249.

18.Cross TM, et al. Performance evaluation of the MinMed continuous glucose monitoring system during patient home use. Diab Technol Ther 2000;2:49–56.

19.Pickup JC, Shaw GS, Claremont DJ. In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer. Diabetes 1989;32:213–217.

20.Jaremko J, Rorstad O. Advances toward the implantable artificial pancreas for treatment of diabetes. Diabs Care 1998;21:444–450.

21.Caduff A, et al. First human experiments with a novel noninvasive, non-optical continuous glucose monitoring system. Biosens Bioelecs 2003;19:209–217.

22.Badugu R, Lakowicz JR, Geddes CD. Ophthalmic glucose sensing: a novel monosaccharide sensing disposable and colorless contact lens. Analyst (England) 2004;129:516–521.

23.Badugu R, Lakowicz JR, Geddes CD. Ophthalmic glucose monitoring using disposable contact lenses—a review. J Fluoresc 2004;14:617–633.

See also ARRHYTHMIA ANALYSIS, AUTOMATED; BIOTELEMETRY; HOME HEALTH CARE DEVICES; PACEMAKERS.

ANALYTICAL METHODS, AUTOMATED

LAKSHMI RAMANATHAN

Mount Sinai Medical Center

LASZLO SARKOZI

Mount Sinai School of Medicine

INTRODUCTION

The chemical composition of blood, urine, spinal fluid, sweat, provides a wealth of information on the well being or illness of the individual. The presence, concentration, and activity of chemical constituents are indicators of various organ functions. Concentrations higher or lower than expected sometimes require immediate attention. Some of the reasons to analyze body fluids:

1.Screening of an apparently healthy population for unsuspected abnormalities.

2.Confirming or ruling out a diagnosis.

3.Monitoring changes during treatment, improvement of condition or lack of improvement.

4.Detecting or monitoring drug levels for diagnosis or maintenance of optimal therapeutic levels.

By the 1950s, demands of clinicians for laboratory tests increased rapidly. Classical methods of manual laboratory techniques could not keep up with these demands. The cost of performing large numbers of laboratory tests by manual methods became staggering and the response time was unacceptable.

The article in the first edition of this Encyclopedia published in 1988 describes the history of laboratory instrumentation during the previous three decades (1). Reviewing that long list of automated instruments, with the exception of a few, all became museum pieces. During the last 15 years the laboratory landscape changed drastically. In addition, new group of automated instruments were introduced during this period. They were developed to perform bedside or near patient testing, collectively called Point of Care Testing instruments. In this period in addition to new testing instruments, perianalytical instrumentation for specimen handling became available. Their combined result is increased productivity and reduction of manpower requirements, which became imperative due to increased cost of healthcare and dwindling resources.

This article will present some financial justification of these investments.

PATIENT PREPARATION, SPECIMEN COLLECTION, AND HANDLING

The prerequisites for accurate testing include proper patient preparation, specimen collection, and specimen handling. Blood specimens yield the most information about the clinical status of the patient though in many cases urine is the preferred sample. For specialized tests, other body fluids that include sweat and spinal fluid are used. When some tests, such as glucose and lipids, require fasting specimens, patients are prepared accordingly.

Common errors affecting all specimens include the following:

Inaccurate and incomplete patient instructions prior to collection.

Wrong container/tube used for the collection. Failure to label a specimen correctly.

Insufficient amount of specimen to perform the test. Specimen leakage in transit due to failure to tighten

specimen container lids.

Interference by cellular elements of blood.

Phlebotomy techniques for blood collection have considerably improved with better gauge needles and vacuum tubes for collection. The collection tubes are color coded with different preservatives so that the proper container can be used for a particular analyte. The cells should be separated from the serum by centrifugation within 2 h of collection. Grossly or moderately hemolyzed specimens may be unsuitable for certain tests. If not separated from serum or plasma, blood cells metabolize glucose and produce a false decrease of5%/h in adults. The effect is much greater in neonates (2). If there is a delay in separating the cells from the serum, the blood should be collected in a gray top tube containing sodium fluoride as a preservative that inhibits glycolysis.

Urine collection is prone to errors as well, some of which include (3):

Failure to obtain a clean catch specimen.

Failure to obtain a complete 24 h collection/aliquot or other timed specimen.

No preservative added if needed prior to the collection.

Once specimens are properly collected and received in the clinical laboratory, processing may include bar coding, centrifugation, aliquoting, testing and reporting of results.

AUTOMATED ANALYZERS

A large variety of instruments are available for the clinical chemistry laboratory. These may be classified in different ways based on the type of technology applied, the test menu, the manufacturer, and the intended application. Depending on the size of the laboratory, the level of

ANALYTICAL METHODS, AUTOMATED

19

automation varies. Clinical chemistry analyzers can be grouped according to throughput of tests and diversity of tests performed and by function, such as immunoassay analyzers, critical care blood gas analyzers, and urinalysis testing systems. Point of Care analyzers vary in terms of accuracy, diversity and menu selection.

Some of the features to consider while evaluating low or high volume analyzers are listed below:

Test menu available on instrument:

Number of different measured assays onboard simultaneously.

Number of different assays programmed/calibrated at one time.

Number of user-defined (open) channels.

Reagents:

Preparation of reagents if any.

Storage of reagents.

On board stability.

Bar-coding for inventory control.

Specimen volume:

Minimum sample volume.

Dead volume.

Instrument supplies:

Use of disposable cuvettes.

Washable/reusable cuvettes.

Clot detection features along with quantitation of hemolysis and turbidity detection.

Auto dilution capabilities of analyzer. Frequency of calibration.

Quality control requirements. Stat capability.

LIS interface.

Maintenance procedures on instrument; anticipated downtime.

Analyzer costs expressed in cost per reportable test.

Our goal is not to review every analyzer available on the market. We have chosen a few of the instruments–vendors. This is by no means endorsing any particular vendor, but merely discussing some of the most frequently utilized features or describing our personal experiences. The College of American Pathologists has provided excellent surveys of instruments and the reader is referred to those articles for more complete details (4).

CHEMISTRY ANALYZERS

Routine chemistry analyzers have broad menus capable of performing an average of 45 (20 to >70) different on board tests simultaneously, selected from an available menu of 26

20

ANALYTICAL METHODS, AUTOMATED

 

Table 1. Automated Analyzers from Different Manufacturers

 

 

 

 

Instrument Type

Generic Menu

Vendor

 

 

 

 

Routine

 

Electrolytes, BUN, Glucose, Creatinine, Protein, Albumin, Lipids,

Abbott, Bayer, Beckman Dade,

chemistry

Iron, Drugs of abuse, Therapeutic drug monitoring, etc.

J&J, Olympus, Roche

Immunoassays

Tumor markers, Cardiac markers, Anemia, B12, Folate and misc.

Abbott, Bayer, Beckman, DPL,

 

 

Endocrine tests

J&J, Olympus, Roche

Critical Care

Blood gases, Cooximetry, Electrolytes Ionized calcium, Lactate,

Abbott, Bayer, Instrumentation Lab,

 

 

Hematocrit

Nova, Radiometer, Roche

 

 

 

 

to >100 different analytes (5,6). Selection is based on test menu, analytic performance, cost (reagents, consumables and labor), instrument reliability (downtime etc.), throughput, and ease of use, customer support and robotic connectivity, if needed. Some automated analyzers from different manufacturers are listed in Table 1.

General Chemistry

Virtually all automated chemistry analyzers offer random access testing, multiple tests can be performed simultaneously and continuously. This is different from batchmode instruments that perform a single test on a batch of samples loaded on the instrument (Abbott TDX and COBAS Bio). Many analyzers are so-called ‘‘open systems’’ that use reagents from either the instrument manufacturer or different vendors. The advantage of these systems being that the customer has a choice of reagent vendors and the reagent can be selected based on performance and cost.

An example of a closed system is a line of analyzers manufactured by Ortho Clinical Diagnostics. The Vitros 950 and the analyzers in this category use a unique, dry chemistry film-based technology developed by Kodak. The slide is a dry, multilayer, analytical element coated on a polyester support. A 10 mL drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers that contain the ingredients for a particular chemical reaction.

The reaction slide (Fig. 1.) for albumin shows the reactive ingredient is the dye (bromcresol green), which is in the reagent layer. The inactive ingredients that include polymeric beads, binders, buffer, and surfactants are in the spreading layer. When the specimen penetrates the reagent layer, the bromcresol green (BCG) diffuses to the spreading layer and binds to albumin from the sample. This binding results in a shift in wavelength of the reflectance maxima of the free dye. The color complex that forms is measured by reflectance spectrophotometry. The amount of albumin-bound dye is proportional to the concentration of albumin in the sample. Once the test is completed the slide is disposed into the waste container.

Some manufacturers close their system by labeling their individual reagent packs with unique barcodes, rejecting packs not distributed by them. Examples of ‘‘open systems’’ include analyzers manufactured by Olympus, Roche (Fig. 2.), Beckman, Dade and Abbott. Many instruments have both open and closed channels allowing greater flexibility in the use of reagents. In addition to diverse menus, open and closed channels, compatibility of analyzers

Slide Diagram

Upper slide mount

Spreading layer (beads)

Reagent layer

bromcresol green dye buffer, pH 3.1

Support layer

Lower slide mount

Figure 1. The Vitros 950 (J&J Diagnostics) slide is a dry, multilayer, analytical element coated on a polyester support. A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers that contain the ingredients for a particular chemical reaction.

Figure 2. The Roche/Hitachi ModularTM analytic system has a theoretical throughput of 3500–5000 tests or 150–250 samples/h. They test 24 different analytes simultaneously with a total menu of > 140 available tests.

with perianalytical technology is becoming an important feature.

Perianalytical systems include front-end automation with specimen processing and aliquoting, track systems or other technologies to move specimens between instruments in the laboratory, and robots to place specimens on and remove them from the analyzers.

Immunoassay Analyzers

Immunoassay systems are presently the fastest growing areas of the clinical laboratory where advances in immunochemical methodology, signal detection systems, microcomputers and robotic processing are taking place at an accelerated pace (7). At present, manufacturers have high volume immunoassay analyzers that can be modularly integrated along with chemistry and hematology analyzers into fully automated laboratory systems. In addition, expanding menus of homogeneous immunoassays allow integration into many laboratories using ‘‘open reagent kits’’ designed for use on automated clinical chemistry analyzers.

One of the several analyzers in this category is the Bayer Advia Centaur (Fig. 3.)

Of the different enzyme immunoassays (EIA) available, only the two homogeneous methods, EMIT and CEDIA have been easily adapted to fully automated chemistry analyzers (8–11). The other EIAs require a separation step to remove excess reagent that will interfere with the quantitation of the analyte. Abbott uses a competitive assay involving a fluorescent-labeled antigen that competes for a limited number of sites on antigen specific antibody. The amount of analyte is inversely proportional

ANALYTICAL METHODS, AUTOMATED

21

to the amount of fluorescence polarization. Chemiluminescence technology is used in the Bayer ACS and Roche Elecsys systems combines very high sensitivity with low levels of background interference. Essentially, it involves a sandwich immunoassay direct chemiluminometric technology, which uses constant amounts of two antibodies. The first antibody in the Lite Reagent is a polyclonal goat anticompound antibody labelled with acridinium ester. The second antibody in the Solid Phase is a monoclonal mouse anticompound antibody, which is covalently coupled to paramagnetic particles. A direct relationship exists between the amount of compound present and the amount of relative light units (RlU) detected by the system (Table 2).

Critical Care Analyzers

Blood gas measurements performed on arterial, venous, and capillary whole blood includes electrolytes and other tests in addition to the gases. These tests are listed in Table 3.

The Nova CCX series combines blood gas measurements with co-oximetry, electrolytes, a metabolic panel and hematology on 50 mL of whole blood. Several blood gas analyzers are utilizing the concept of ‘‘Intelligent Quality Management’’ whereby the analyzers run controls automatically at specified time intervals set by the operator. If a particular analyte is not within the specified range, the analyzer will not report out any patient results on the questionable test. Selected blood gas and critical care analyzers are listed in Table 4.

The unique specimen and turnaround time requirements for blood gases have prevented the tests from

Figure 3. The Bayer Advia Centour system has large on-board capacity for reagents and supplies combined with automated maintenance and monitoring features streamline operations. Categories such as fertility, therapeutic drug monitoring, infectious disease, allergy, cardiovascular, anemia, and oncology, therapeutic drug monitoring and thyroid tests are available. Up to 30 different reagent packs can be placed on the instrument. It has a throughput of 240 tests/h.

22

ANALYTICAL METHODS, AUTOMATED

 

 

 

 

Table 2. Immunoassay Analyzers

 

 

 

 

 

 

 

 

 

 

Manufacturer

 

Model

Methodology

 

 

 

 

 

 

 

 

Abbott diagnostics

 

Axsym

FPIA, MEIA

 

 

 

 

TDX, IMX

FPIA

 

 

 

 

ADX

FPIA

 

 

 

 

Architect

Chemiluminescence

 

 

Bayer Diagnostics

 

ACS 180

Chemiluminescence

 

 

 

 

Centaur

Chemiluminescence

 

 

 

 

Immuno 1

EIA

 

 

Beckman Coulter

 

Access

EMIT

 

 

 

 

LX-20

EMIT

 

 

 

 

DCI

Chemiluminescence

 

 

Boehringer Manheim ES-300

EIA

 

 

 

 

 

Elecsys

Chemiluminescence

 

 

Dade Behring

 

Opus Magnum

EIA

 

 

 

 

Stratus

FIA

 

 

 

 

ACA

EIA, Petinia

 

 

 

 

ACA

EIA, turbidimetric

 

 

Diagnostic Product Corp.

Immulite

Chemiluminescence, EIA

 

 

Nichols Diagnostics CLS ID

Chemiluminescence

 

 

 

Ortho Clinical

 

Eci

Chemiluminescence

 

 

 

 

 

 

Table 3. Test Menus for Critical Care Analyzers

 

 

 

 

 

 

 

 

 

Category

 

Tests Included

 

 

 

 

 

 

 

Blood gases

pH, pCO2, pO2 and other calculated parameters

 

 

Electrolytes

Sodium, potassium, chloride, bicarbonate, ionized calcium

 

 

Co-oximetry

Carboxyhemoglobin, methemoglobin, total hemoglobin, O2 saturation

 

 

Metabolic panel

Glucose, blood urea nitrogen, creatinine, lactate

 

 

Hematology

Hematocrit, hemoglobin, activated clotting time

 

 

 

 

 

 

being performed in combination with general chemistry tests.

Point of Care Testing

Point of care testing (POCT) is defined as laboratory diagnostic testing performed close to the location of the patient. Recent advances over the last decade have resulted in smaller, more accurate devices with a wide menu of tests (12,13). Today POCT can be found from competitive sports to the prison system, from psychiatric counseling to preemployment and shopping mall health screening. Use of POCT devices can be found in mobile transport vehicles such as ambulances, helicopters cruise ships and even the space shuttle.

The advantage of POCT is the ability to obtain extremely rapid laboratory results. However, it is necessary to be aware of the limitations of POCT devices in clinical practice. Venous blood samples often have to be drawn and sent to the main laboratory for confirmation if the results

are not within a certain specified range. Another disadvantage of POCT is costs.

In compliance with the guidelines set by federal, state regulatory agencies and the College of American Pathologists (CAP), point of care testing programs are usually overseen by dedicated staff under the direction of the central laboratory. The responsibilities of the POCT staff include education and training of hospital staff, troubleshooting of equipment, maintaining quality control and

Table 4. Partial List of Critical Care Instruments

Vendor

Instrument

 

 

Abbott (iSTAT)

iSTAT

Bayer

200,300 800 series, Rapidpoint

Diametrics

IRMA

Instrumentation Lab

1600, 1700 series, Gem series

NOVA

Stat profile series, CCX

Radiometer

ABL series

Roche (AVL)

900 series, Omni and Opti series

 

 

Figure 4. The Roche Accu-Check is a small, easy to use blood glucose meter; it is widely used by our Point of Care Testing program. Test results are downloaded to the Laboratory Information System.

quality assurance standards. For a successful POCT program, the laboratory and clinical staff need to effectively work together.

The handheld Accu-Chek POCT device is shown on Fig. 4.

The most widely used point of care tests are bedside glucose testing, critical care analysis, urinalysis, coagulation, occult blood and urine pregnancy testing. Selected point of care devices are listed in Table 5. Other available POCT tests: cardiac markers, pregnancy, influenza A/B, Rapid Strep A, Helicobacter pylori, urine microalbumin and creatinine.

CLINICAL LABORATORY AUTOMATION

Historical Perspective

Along with innovations in instrumentation, automating perianalytical activities such as centrifuging, aliquoting,

Table 5. Selected Point of Care Devices

Test

Vendor

 

 

Bedside glucose test

Abbott (Medisense PCx)

 

Bayer

 

Ortho (Lifescan: One Touch)

 

Roche

Critical care

Abbott (iSTAT)

 

Bayer (Rapidpoint)

 

IL (Gem series)

Coagulation

Abbott (iSTAT)

 

Bayer (Rapid point)

 

Hemosense

 

ITC (Hemochron series)

 

Medtronics (Hepcon)

 

Roche (Coaguchek)

Fecal occult blood

Helena

 

Smithkline Diagnostics

Urinalysis

Bayer (Multistix and Clintek)

 

Roche (Chemstrip and CUA)

 

 

ANALYTICAL METHODS, AUTOMATED

23

delivering specimens to the automated testing instruments, recapping and storing plays significant role in the modern clinical laboratory (14). Robotic systems that automate some or virtually all of the above functions are available. Automated laboratory and information systems offer benefits in terms of speed, operating efficiency, integrated information sharing and reduction of error.

However, the individual needs of each laboratory have to be considered in order to select the optimum combination of instrumentation and perianalytical automation. For small laboratories, front-end work cell automation may be applied economically.Forlargecommercialreference labsandhospital labs, total laboratory automation (TLA) is appropriate where samples move around the whole lab, or from place to place (15).

Clinical laboratory automation evolved with the development of the hematology ‘‘Coulter Counter’’ and the chemistry ‘‘AutoAnalyzer’’ in the 1950s. Automated cell counting by the Coulter involved placing a sample of whole blood in a hemocytometer and using a microscope to count the serial passage of individual cells through an aperture. Likewise, the automated analysis of patient samples for several chemistries dramatically changed the testing process in the chemistry laboratory.

In the 1980s in Japan, Dr. Sasaki’s group developed a point-to-point laboratory system that was based on overhead conveyor transportation, delivering specimens placed in 10 position racks (16). These initial designs are the basis of several automation systems available today.

Automation Options and System Design

Available options for automation include the following:

Interfaced instruments (some can be operated as stand alone analyzers and later linked to a modular system).

Modular instruments (including, processing, and instrument work cells).

Multidiscipline platforms (including multifunction instruments and multiwork cells).

Total laboratory automation robotics system that automates virtually all routine functions in the laboratory.

Automation system design usually rests on the needs of the user. However, the following concepts should be considered:

Modern information technology with hardware and operating systems that are vertically upgraded.

Transportation system management at both the local level (device) and overall system level.

Specimen tracking so that any specimen can be located in the automation system.

Reflex testing where an additional test can be performed at the same instrument or the specimen can be retrieved to another instrument.

Information systems agreement with the Laboratory Information System (LIS).

The ability to interface between the hospital LIS and the laboratory automation system (LAS) has been significantly

24 ANALYTICAL METHODS, AUTOMATED

enhanced by the implementation of the HL7 system-to- system interface. The National Committee on Clinical Laboratory Standards (NCCLS) has issued a proposal level standard (Auto 3 –P) that specifies the HLA interface as the system-to-system communications methodology for connecting an LIS and an LAS (17–21).

NCCLS Guidelines

Components of an optimized laboratory automation system per NCCLS may include:

Preprocessing specimen sorting. Automated specimen centrifugation. Automated specimen aliquoting. Specimen–aliquot recapping/capping. Specimen integrity monitoring. Specimen transportation. Automated specimen sampling.

Automated specimen storage and retrieval.

It is also recommended that process control software should support:

Specimen routing.

Reflex testing.

Repeat testing.

Rules based processing.

Patient data integration.

Available Automation Systems

In the mid-1990s, several laboratory automation technologies implemented hardware-based automation solutions that were centered on defining a limited number of specimen containers compatible with the transportation system. By limiting the number of specimen containers, the hardware can be better defined and more efficient. The original Coulter IDS automation system and the original Hitachi CLAS were based on fixed, rigid or hard-coded hardware technologies.

In the Hitachi CLAS and modular systems, the automation transportation devices use the Hitachi 747 fiveplace specimen container rack. In order to move the specimen container rack from one analyzer to the next, the automation system must carry along four other patient specimens. The requirement to carry along additional specimens along with the target specimen creates significant mathematical complexity in routing and scheduling of tests. The use of a simple specimen container per specimen carrier model allows the routing of an individual specimen to a workstation without interrupting the flow of other individual specimens in the system.

Total laboratory automation is used to describe the Beckman Coulter IDS system (22). We have two parallel systems in our laboratory (Fig. 5). The basic components include the inlet module, where samples are placed, a centrifuge, serum level sensor, decapping unit, aliquoterlabeler units, outlet units, refrigerated storage unit

and a disposal unit. A line PC that interacts with the LIS and all the individual components of the automation system controls the entire system. Each of the automated instruments has their own individual attachment for the handling of specimens being received from the robotic system. View of our automated (perianalytical and analytical) clinical laboratory is shown on Fig. 6.

Work Cell Technologies

The work cell model can be divided into two basic approaches. The first includes all instruments from the same discipline (Chemistry). The second approach is the development of a platform that includes multiple disciplines. An example of this is the Bayer Advia work cell in which chemistry, hematology, immunoassay, and urinalysis processing can take place on one platform. However, this work cell does not have front-end specimen processing and handling capability. Several automated work cells are available in the market at the present time. They include Abbott (Abbott hematology work cell), Beck- man-Coulter (Acel-Net work cell), Bayer (Advia work cell), Johnson and Johnson (lab interlink labframe select), and Roche (modular system). The work cell technology varies from simple specimen transportation to complex specimen management.

LABORATORY AUTOMATION-A FINANCIAL PERSPECTIVE

Several studies are being reported on the financial aspects of automation. The most significant impact has been the reduction in FTEs and improvement in turnaround time. A retrospective analysis of 36 years of the effects of initially automation followed by total laboratory automation in the clinical chemistry laboratory at Mount Sinai Medical Center indicated that workload was significantly increased with a reduction of personnel (23). We present these productivity changes in Table 6.

Increased productivity resulted in significant reduction of performing laboratory tests (Table 7).

The effect of increased productivity is illustrated by the drastic reduction of cost/test (Fig. 7)

CALCULATIONS FOR NET PRESENT VALUE OF THE MOUNT SINAI CHEMISTRY AUTOMATION PROJECT (FIG. 8)

Net Present Value

The Net Present Value (NPV) is the value of the net cash flows generated by the project in 1998 $ (the year in which the project was initiated). The NVP is calculated by discounting the value of the annual cash flows [using values taken from the Present Value Interest Factor (PVIF) table for a given project length and cost of capital] to the purchasing value of the dollar at the date of inception of the project (1998). The length of the investment project is a conservative estimate of the useful economic lifetime of the investment project. In this case, we believe that after 8 years additional investments in upgrades

 

 

 

 

 

 

 

 

 

 

 

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g

 

 

6 6

12 6 6

9−T

 

 

 

 

 

9

9

9−T

12 3

9

6 6 9−T

6 12 6

 

−9

 

 

200-747

 

 

 

 

0

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

9−T

6

 

 

 

 

 

 

 

 

Figure 5. Floor plan of our Total Laboratory Automation. (a) Sample reception. Specimens are picked up, 5 at a time, from 50-position racks and loaded into individual tube holders. A bar-code verification unitdetermines thelegibility ofthe labels, determines ifthe specimenisontherightprocessing location, rejects the suspect samples into a holding area and accepts the correct ones by a message to the Laboratory Information System:‘‘Specimen Received’’. (b) Sample transport. The transport lanes are conveyor belts that move the samples about the system. (c) Centrifugation. Samples are loaded and unloaded automatically. The rotor has 50 positions. In our laboratory 350 specimens/h can be processed in these centrifuges. (d) Serum level detection. After centrifugation the samples are lowered into an optical well and based on the transmitted information the amount of the available serum is calculated.

(e) Cap removal. A gentle rocking motion removes the cups without creating potentially hazardous aerosols. (f) Tube labeling and sample aliquoting. For each primary serum sample secondary aliquot tuber are prepared. The tube labeler prints a bar-code label and applies it to each aliquot tube. The number of aliquot tubes is defined by the system. Disposable pipette tips transfer the serum from the primary to the secondary (aliquot) tubes. The primary tubes are directed to a storage unit. (g) Instrument connections. Several instruments are connected to the transport system. Connection units load and unload samples. Samples not going to the analyzer can continue down the main line.

(h) Cap replacement. When the testing of a secondary aliquot tube has been completed, the tube is directed toward an outlet unit, stockyard or storage locker. Before storage, the tube can receive a clean cap. (i) Refrigerated Sample storage. It holds up to 3000 tubes. Samples can be retrieved automatically through a request in the computer and sent to the location requested by the operator.

26 ANALYTICAL METHODS, AUTOMATED

Figure 6. A portion of the Chemistry automated Core Laboratory at The Mount Sinai Hospital, New York.

beyond normal maintenance may be required. The cost of capital used was the interest rate of the lease taken out to finance the project. The relevant calculations are shown below:

 

12000

 

 

 

 

 

0.9

 

 

Specimens/employee/year

 

 

79c

10,066

0.8

 

 

 

 

 

 

10000

 

 

 

 

 

(1965$)Cost/test

 

 

 

 

 

 

 

 

 

 

 

 

 

 

0.7

 

 

 

 

 

 

 

 

 

 

 

 

8000

 

 

 

 

+27%/year

0.6

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

45c

 

0.5

 

 

 

6000

 

 

 

5,529

0.4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

5,268

 

 

 

 

1997

0.3

 

 

 

 

 

 

4000

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1965

 

22c

21c

–9.5%/year

0.2

2000

2,560

2,745

 

 

15c

 

0.1

 

 

 

 

 

 

1960

1970

1980

1990

2000

2010

 

 

 

 

Year

 

 

 

Figure 7. Automation increased Productivity and reduced cost. While the number of specimens processed increased from 2.500 to 10,000 specimens/year the cost/test was reduced from $0.79 to 0.15 (in 1965$).

Positive Cash Flows

Positive cash flows are those that represent money saved and/or costs avoided as the result of the chemistry auto-

1.Total cost of the lease (capital and interest):

2.Total interest paid over the life of the lease:

3.Annual interest payments:

4.Interest rate paid on lease:

Negative Cash Flows

Negative cash flows represent money spent on the project. This includes capital outlays, lease payments ($3,140,000 or $741,921/year for 5 years, represented the portion on chemistry automation), project-related expenses (annual maintenance contract, years 1999 and 2000 ¼ $74,240 annually, 2001–2005 ¼ $39,000 annually.

Table 6. Increased Productivity

$121,963/month 60 months

¼

$7,318,480

$7,318,380 $6,194,650

¼

$1,123,730

$1,123,730/5 years

¼

$ 224,730

($224,746/$6,194,650) 100

¼

3,628%

 

 

 

 

 

mation project. There are recurring positive cash flows, resulting from savings that are essentially perpetual, such as salaries and benefits of workers replaced permanently by the chemistry automation project. Savings realized in a given year that are not expected to be repeated in subsequent years are nonrecurring positive cash flows. Staff pay raises during the years 1998, 1999, 2000, and 2002 were

 

 

 

 

No. of

No. of

No. of

Total No. of

Year

Tech Staff

Other Staff

Total Staff

Tests/Tech

Tests/tot. Staff

Tests/Specimen

Specimens

 

 

 

 

 

 

 

 

1965

19

6.00

24.00

14,000

10,600

4.2

2,560

1970

34

17.00

51.00

36,205

24,150

8.8

2,745

1980

39

22.00

61.00

82,359

53,732

10.0

5,268

1997

38

17.00

55.00

94,058

66,099

11.8

5,529

2000

29

13.00

42.00

151,190

104,558

10.4

10,066

2002

29

39.00

35.00

169,582

128,530

10.5

12,190

 

 

 

 

 

 

Table 7. Cost/Test Reduction

 

 

 

 

 

 

 

 

 

 

 

 

 

Year

Tech Salary, $

Salary $/Test

Supplies $/Test

Total $/Test

Salary 1965 $/Test

Supplies 1965 $/Test

Total 1965 $/Test

 

 

 

 

 

 

 

 

1965

5,170

0.70

0.19

0.79

0.70

0.09

0.79

1970

9,114

0.38

0.17

0.55

0.31

0.14

0.45

1980

16,500

0.37

0.20

0.57

0.14

0.08

0.22

1997

38,000

0.66

0.41

1.07

0.13

0.08

0.21

2000

41,000

0.45

0.36

0.81

0.08

0.07

0.15

2002

44,000

0.38

0.34

0.72

0.07

0.06

0.13

 

 

 

 

 

 

 

 

 

NPV Profile – Chemistry

$2,000,000

automation

 

NPV =

 

$1,500,000

When NPV = 0

NPV

Internal rate of

return (IRR) = 22

$1,000,000

 

$500,000

$

0

4

8

1

1

2

2

2

3

Interest rate (%)

Figure 8. The Internal Rate of Return for the Chemistry Automation project was a remarkable 22%.

financed directly from chemistry automation project savings. These amounts are not reflected in the net salary and benefits savings. As such they are positive cash flow, since they represent costs covered by the automation savings that otherwise would have had to be financed through other sources.

The NPV Profile and Internal Rate of Return

The interest rate employed to discount the value of cash flows to the baseline year (1998) is the marginal cost of capital (the interest rate of the lease), which is 4%. The interest rate at which the NPV equals zero is especially interesting. This is called the internal rate of return (IRR) of the project. For all interest rates below the IRR, the NPV will generate positive values. In order to determine the IRR, we construct an NPV profile for different interest rates and locate the rate where the NPV crosses the X axis where the NPV ¼ 0 (Fig. 8.). It shows that the chemistry automation project can tolerate interest rates up to 18.0% (the IRR) and still generate positive returns.

The Payback Period and Average Return on Investment

Although the NPV and IRR are vastly superior indicators of project profitability because of their use of discounted cash flows, the payback period and return on investment (ROI) are still key determinant of project viability by a majority of financial managers.

The Payback Period. After 8 years the raw dollar value of positive cash flows is $5,371,743 versus negative cash flows of $4,0053,085. The payback period therefore:

8 years ð$4; 053; 085=$5; 371; 743Þ

8 years 0:755 ¼ 6:04 years

Average ROI

$4,053,085/8 years ¼ $506,635/ year

Average Annual

Cash Outlay:

 

ANALYTICAL METHODS, AUTOMATED

27

Average Annual

(5,371,743 $4,053,085)/8 years ¼

Net Return:

$164,822

 

Average ROI:

($164,832/$506,635) 100 ¼ 32.5%

CONCLUSIONS

Productivity is a key issue for labs.

The major financial benefit of automation is increased productivity.

Perianalytical automation increased our chemistry productivity by 120% (from 5,530 to 12,190 specs/tech/ year).

Perianalytical automation reduced our chemistry labor cost/test by 42% (from 66¢ to 38¢/test).

Automation is a key solution for staff shortages. Speedy implementation, speedy labor reductions and

speedy revenue generation improve financial performance.

To achieve financial success, laboratorians must understand key financial principles.

ACKNOWLEDGMENTS

We thank E. Simson for practical advice on the financial perspective and M. Gannon for teaching us the meaning and calculation of the Net Present Value.

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