원저 Lab Med Online Vol. 4, No. 2: 77-84, April 임상화학 Beckman Coulter AU5822 자동화학분석기의수행능평가 Performance Eva

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1 원저 Lab Med Online Vol. 4, No. 2: 77-84, April 2014 임상화학 Beckman Coulter AU5822 자동화학분석기의수행능평가 Performance Evaluation of Beckman Coulter AU5822 Automated Clinical Chemistry Analyzer 김수경 정태동 이우창 전사일 민원기 Soo-Kyung Kim, M.D., Tae-Dong Jeong, M.D., Woochang Lee, M.D., Sail Chun, M.D., Won-Ki Min, M.D. 울산대학교의과대학서울아산병원진단검사의학과 Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea Background: AU5822 Automated Clinical Chemistry Analyzer (Beckman Coulter, USA) is a fully automated analytical platform designed for the analysis of general chemistry, specific serologic proteins, therapeutic drug monitoring, and drug abuse testing. AU5822 is a high-throughput system that can process up to 5,800 tests per hour and is easy to maintain. In this study, we evaluated the performance of AU5822 on 31 analytes. Methods: The precision, linearity, correlation, and sample carryover of 31 analytes were evaluated in accordance with the guidelines of the Clinical Laboratory Standards Institute (CLSI). Lyphochek (Bio-Rad Laboratories Inc., USA), Liquichek (Bio-Rad Laboratories Inc.), Validate (Marine Standard Company, USA), and patient sera were used in the analysis. For the correlation study, we carried out a comparison of AU5822 and Cobas 8000 Modular Analyzer (Roche, Switzerland). Results: The coefficients of variation of all samples showed values below 5%. The coefficient of determination (R 2 ) was 0.99, with linearity in the clinically important range. The comparison with Cobas 8000 showed a good correlation, with a correlation coefficient of >0.975 for all of the analytes, excluding sodium that had a correlation coefficient of The test values of percentage sample carryover were less than 0.89%. Conclusions: AU5822 performed well in terms of precision, linearity, comparison, and sample carryover in the established assays for 31 analytes. Therefore, Beckman Coulter AU5822 Automated Clinical Chemistry Analyzer is expected to be useful for routine chemistry analysis in hospitals with large test volumes. Key Words: Analytical performance, Beckman Coulter AU5822, Chemistry analyzer, Evaluation 서론 검사의질향상과검사시간의단축을위해여러종류의자동화 학분석기가개발되고있다. 또한검사양의증가및검사비용절감 정책에따라많은검사실에서고도로자동화된장비를필요로하 Corresponding author: Sail Chun Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul , Korea Tel: , Fax: , sailchun@amc.seoul.kr Received: April 26, 2013 Revision received: November 20, 2013 Accepted: November 20, 2013 This article is available from , Laboratory Medicine Online This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 고있다 [1, 2]. 이에검사의목적과각병원의환경에맞는분석장비를찾아검사실에맞게최적화하는것이무엇보다중요한검사업무의하나로인식되고있다 [2]. 본원에서는외래환자들의일반화학검사에 TBA-200FR (Toshiba Medical Systems, Tokyo, Japan) 자동화학분석기를사용하고있었으나장비의노후화로인한유지보수의어려움이있었다. 따라서당일외래환자의임상화학검사가집중되는시간대에검사소요시간 (turnaround time, TAT) 을준수하고, 검사실공간을효율적으로사용하기위해최근 TBA-200FR 장비 5대를 AU5822 (Beckman Coulter, Brea, CA, USA) 2대로대체하였다. AU5822는 AU5800 모듈 2개와이온선택전극 (ion selective electrode, ISE) 2개로구성된장비로시간당검사처리건수가최대 5,800건에이른다. 저자들은최근새로도입한 Beckman Coulter AU5822의 31개일반화학검사항목에대해검사의정밀도, 직선성, 기존장비와의상관성, 검체간교차오염률을평가하고자하였다. eissn

2 대상및방법 1. 검사장비및검사항목 Beckman Coulter AU5822는일반화학검사, 혈청단백질검사및치료적약물농도검사를수행할수있는대용량, 다항목의선택적임상화학자동분석기이다. 본연구에서는알부민, 알칼리성포스파타제 (alkaline phosphatase, ALP), 알라닌아미노트란스페라제 (ALT), 아밀라제, 아스파탐아미노트란스페라제 (AST), 혈액뇨소질소, 칼슘, 콜레스테롤, 크레아틴키나제, 염화물 (chloride), 이산화탄소, 크레아티닌, C-반응단백질 (C-reactive protein), 직접빌리루빈, 감마글루타밀전이효소 (gamma glutamyl transferase, GGT), 포도당, 고밀도지단백 (HDL), 고예민도 C-반응단백질 (high-sensitivity C-reactive protein), 철, 칼륨, 락트산탈수소효소 (lactate dehydrogenase), 저밀도지단맥 (LDL), 리파제, 마그네슘, 나트륨, 인, 총빌리루빈 (total bilirubin), 중성지방, 총단백, 요산, 불포화철결합능등총 31개항목에대해검사를시행하였다. 각검사항목의측정원리는 Table 1과같다. 2. 평가방법 1) 정밀도 (Precision) 정밀도는 C-반응단백질과고예민도 C-반응단백질외의 29항목에대해서 Lyphochek Unassayed Chemistry Control (Human) Level 1과 Level 2 (Bio-Rad Laboratories Inc., Hercules, CA, USA) 를사용하여 Clinical and Laboratory Standards Institute (CLSI) EP5-A2 지침에따라평가하였다 [3]. C-반응단백질은 Liquichek Immunology Control Level 1, Level 2와 Level 3 (Bio-Rad Laboratories Inc.) 를사용하였으며, 고예민도 C-반응단백질은 Liquichek Cardiac Markers Plus Control Level 1, Level 2와 Level 3 (Bio-Rad Laboratories Inc.) 를사용하였다. 20일간각농도에대해 1일 2회, 1 회 2번씩반복측정하였다. 하루 2회검사는 2시간이상의간격을두고오전과오후로나누어실시하였다. 측정된결과로각농도별평균, 표준편차, 검사내변이계수 (within run coefficient of variation, CV), 검사간변이계수 (between run CV), 검사일간변이계수 (between day CV), 총변이계수 (total CV) 를계산하였다. 정밀도의판정기준은 CLIA에서제시하는기준을따랐다 [4]. 2) 직선성 (Linearity) 직선성은 CLSI EP6-A의지침에따라평가하였다 [5]. C-반응단백질, 고예민도 C-반응단백질, 불포화철결합능외의 28개검사항목은 Validate GC Linearity Test Set (Marine Standard Company, Windham, ME, USA) 를사용하여평가하였다. C-반응단백질과고예민도 C-반응단백질은각각 CRP Latex Calibrator Normal Set Table 1. Analytical methods of Beckman Coulter AU5822 Analyte Method Albumin Alkaline phosphatase ALT Amylase AST Blood urea nitrogen Calcium Carbon dioxide Chloride Cholesterol C-reactive protein Creatine kinase Creatinine Direct bilirubin GGT Glucose HDL hs-crp Iron Lactate dehydrogenase LDL Lipase Magnesium Phosphorous Potassium Sodium Total bilirubin Total protein Triglycerides UIBC Uric acid (Beckman Coulter, Brea CA, USA), CRPH Latex Calibrator High Sensitivity Set (Beckman Coulter) 를사용하여검사하였다. 불포화 철결합능은기존에측정한저농도와고농도검체하나씩을 CLSI EP6-A 지침에따라 4:0, 3:1, 2:2, 1:3, 0:4 의비율로섞어검사하였다 [5]. 31 가지검사항목각각에대해제조사가제시한측정가능범위 (analytical measurement range) 를고려하여저농도에서고농도까 지 5 가지농도를 4 회반복측정하였다. 측정된결과로다항회귀분 석을시행하여평가하였다. BCG Dye-binding pnpp, AMP buffer IFCC UV without P5P Kinetic color (CNPG3) IFCC UV without P5P Urease with GLDH (coupled enzymes) Cresolphthalein complexone Enzymatic ISE, diluted (indirect) Enzymatic Immunoturbidimetric method IFCC NAC-activation (kinetic UV) Kinetic alkaline picrate (Jaffe reaction) Diazonium salt (DPD) Szasz Hexokinase, UV Enzymatic colorimetric test (immunoinhibition) Immunoturbidimetric method TPTZ Lactate to pyruvate Enzymatic colorimetric test Kinetic Color Xylidyl Blue Method Phosphomolybdate, UV ISE, diluted (indirect) ISE, diluted (indirect) Diazonium salt (DPD) Biuret method Enzymatic GPO-POD (without glycerol and sample blanks) Nitroso-PSAP Uricase Abbreviations: AMP, 2-amino-2-methyl-1-propanol; BCG, bromo-cresol green; CNPG3, 2-chloro-4-nitrophenyl-α-D-maltotrioside; DPD, 3,5-dichlorophenyldiazonium tetrafluoroborate; GGT, gamma-glutamyl transferase; GLDH, glutamate dehydrogenase; GPO-POD, glycerol-3-phosphate oxidase peroxidase; hs-crp, high-sensitivity C-reactive protein; IFCC, international federation of clinical chemistry; ISE, ion-selective electrode; NAC, N-acetyl cysteine; Nitroso-PSAP, 2-Nitroso-5-(N-propyl-N-sulfopropylamino)phenol; P5P, pyridoxal-5-phosphate; pnpp, p-nitrophenyl phosphate; TPTZ, 2,4,6-tripyridyl-s-triazine; UIBC, unsaturated iron binding capacity. 78

3 3) 상관성 (Method comparison) 각검사항목에대하여 CLSI EP9-A2 지침을참고하여 60명의환자검체를대상으로평가하였다 [6]. 기준장비는기존검사실에서사용중인 Cobas 8000 modular analyzer (Roche diagnostics, Basel, Switzerland) 로하였다. 각장비에서 2회반복측정한값의평균값으로회귀방정식과상관계수 (coefficient of correlation, r) 를산출하였다. 상관계수가 이상인경우상관성이있다고판단하였다. 4) 검체간교차오염률 (sample carryover) 각검사항목에대하여 CLSI EP10-A2 에따라고농도물질및저농도물질을각각 4회연속측정하여검체간교차오염률을확인하였다 [7]. %carryover = [L1-(L3+L4)/2 100/[(H2+H3)/2-(L3+L4)/2] 공식을이용하여검체간 %carryover를산출하였고, 1.0% 를기준치로삼았다 [8]. 3. 통계분석통계분석은 EP Evaluator Release 9 (David G. Rhoads Assoc., Kennett square, PA, USA) 과 Microsoft Excel 2007 (Microsoft corporation, Redmond, WA, USA) 을사용하였다. 결과 1. 정밀도 검사항목별평균, 표준편차, 검사내변이계수, 검사간변이계수, 검사일간변이계수, 총변이계수는 Table 2와같다. 모든검사항목에서총변이계수는 5% 미만의결과를보였다. 검사내정밀도의변이계수는 Level 1은 % 였고, Level 2는 % 였다. 검사간정밀도의변이계수는 Level 1에서 %, Level 2는 % 였다. 2. 직선성 31가지검사항목모두임상적으로의미있는범위내에서결정계수 (coefficient of determination, R 2 ) 가 0.99 이상으로우수한직선성을보였다 (Table 3). 3. 상관성 AU5822와기준장비로측정한일반화학항목과전해질항목에서나트륨의상관계수는 이었고, 나트륨을제외한나머지 30 가지검사항목의상관계수는 이상이었다 (Fig. 1). 4. 검체간교차오염률각각의검사항목마다측정한 %carryover 값은 0.89% 미만이었다. 고찰 CLSI는기기의정밀도적합성평가에있어서구체적허용오차의한계설정시각기관의실정에맞게규정하도록제시하고있다 [3]. Clinical Laboratory Improvement Amendment (CLIA) 88에서제안하는정밀도의허용오차한계는그폭이 ±25% 정도로상당히넓다 [9, 10]. 이에검사실내변이계수를 CLIA 치의 1/3 또는 1/4 이하로제안하는연구들도있다 [11, 12]. 본연구에서두가지표준물질 (C-반응단백질과고예민도 C-반응단백질은세가지표준물질 ) 을이용하여실시한정밀도평가에서 31가지검사항목모두총변이계수가 CLIA에서제시하는일반화학검사항목의정밀도기준을만족하였다 [4]. 직선성평가에서모든항목이임상적으로중요한농도범위에서우수한직선성이확인되었다. ALP, ALT, 아밀라제, AST, 콜레스테롤, 크레아틴키나제, 이산화탄소, GGT, 고예민도 C-반응단백질, 중성지방은제조사가제시하는직선성의범위또는더높은농도까지의직선성이검증되었다. 그러나 BUN, HDL, LDL, 리파제, 불포화철결합능은직선성평가에사용하였던상품화된물질의농도가제조사에서제시한범위를모두포함하지못하여제한된범위에서만직선성을확인하였다. 상관성평가에서나트륨을제외한모든검사항목의상관계수가허용범위 이상으로 AU5822와 Cobas 8000 간의우수한상관성이관찰되었다. 나트륨의상관계수는 로장비간상관성평가기준인상관계수 미만이었다. 나트륨측정방법으로두장비모두간접이온선택전극법 (indirect ion selective electrode) 을사용하고있다. 따라서이러한검사결과의차이는검사방법보다는상관성평가시사용한검체의나트륨범위가좁아발생한것으로생각된다. AU5822에서검사는모검체에서자검체로분주된후분석이진행되는데, 일회용큐벳이나일회용피펫을사용하지않으므로검체사이에교차오염의가능성이있다. 연구결과검체간교차오염평가에서는교차오염률이 31가지검사항목모두기준치 1.0% 보다낮아 AU5822 장비의검체간교차오염영향은매우낮을것으로판단된다. 장비의운용방법은간단하며검사진행중에검사자의추가조작은거의없었다. 검체이송통로는반송통로, 추월통로, 일반통로세가지로분화되어융통성있게검체를이송할수있다. 또한농축시약을사용하여, 최소반응액량이 80 µl로시약비용을절감할수있는장점이있다. 이처럼기존의장비 5대를상대적으로시간 79

4 Table 2. Precision profile of Beckman Coulter AU5822 Analyte Unit Level Mean SD CV (%) Within-run Between-run Between-day Total Albumin g/dl Alkaline phosphatase IU/L ALT IU/L Amylase U/L AST IU/L Blood urea nitrogen mg/dl Calcium mg/dl Cholesterol mg/dl Creatinine kinase IU/L Chloride mmol/l Carbon dioxide mmol/l Creatinine mg/dl C-reactive protein mg/dl Direct bilirubin mg/dl GGT IU/L Glucose mg/dl HDL mg/dl hs-crp mg/dl Iron µg/dl Potassium mmol/l Lactate dehydrogenase IU/L LDL mg/dl Lipase U/L Magnesium mg/dl (Continued to the next page) 80

5 Table 2. Continued CV (%) Analyte Unit Level Mean SD Within-run Between-run Between-day Total Sodium mmol/l Phosphorus mg/dl Total bilirubin mg/dl Triglyceride mg/dl Total protein g/dl Uric acid mg/dl UIBC µg/dl Abbreviations: CV, coefficient of variation; SD, standard deviation. Table 3. Linearity studies using Beckman Coulter AU5822 Analyte Unit Linear range specified by the manufacture Test range Observed linear range Slope Intercept R 2 Albumin g/dl ALP IU/L ALT IU/L Amylase U/L AST IU/L BUN mg/dl Calcium mg/dl Cholesterol mg/dl Creatinine kinase IU/L Chloride mmol/l CO2 mmol/l Creatinine mg/dl CRP mg/dl Direct bilirubin mg/dl GGT IU/L Glucose mg/dl HDL mg/dl hs-crp mg/dl Iron µg/dl Potassium mmol/l LDH IU/L LDL mg/dl Lipase U/L Magnesium mg/dl Sodium mmol/l Phosphorus mg/dl Total bilirubin mg/dl Triglyceride mg/dl Total protein g/dl Uric acid mg/dl UIBC µg/dl Abbreviations: ALP, alkaline phosphatase; BUN, blood urea nitrogen; LDH, lactate dehydrogenase; R 2, coefficient of determination. 81

6 A B C D E F G H I J K L M N O P Q R S T Fig. 1. Linear regression plots comparing the results obtained for 31 analytes by using Beckman Coulter AU5822 and cobas 8000 Modular Analyzer. The following analytes were analyzed: (A) albumin, (B) ALP, (C) ALT, (D) amylase, (E) AST, (F) BUN, (G) calcium, (H) cholesterol, (I) creatinine kinase, (J) chloride, (K) CO2, (L) creatinine, (M) CRP, (N) hs-crp, (O) direct bilirubin, (P) GGT, (Q) glucose, (R) HDL, (S) iron, (T) potassium. (Continued to the next page) 82

7 U V W X Y Z AA AB AC AD AE Fig. 1. Continued. (U) LDH, (V) LDL, (W) lipase, (X) magnesium, (Y) sodium, (Z) phosphorus, (AA) total bilirubin, (AB) triglyceride, (AC) UIBC, (AD) total protein, (AE) uric acid. The blue line represents the linear regression and the gray line depicts a theoretical line with a slope of 1.0 and a y-intercept of 0. 당검사처리율이높은장비 2대로대체함으로서검사실공간을더욱효율적으로사용할수있게되었고, 장비점검및관리에필요한인력과시간도줄일수있게되었다. 결론적으로 Beckman Coulter AU5822의수행능평가결과정밀도와장비간상관성이우수하였다. 또한임상적으로유용한범위내에서직선성을확인하였고, 검체간교차오염률이낮았다. 그러므로본임상화학자동화검사장비는검사건수가많은대형병원의검사실에서사용자편의적인검사환경을제공하고, 정확하고빠른검사결과를보고할수있을것으로판단된다. 요약 배경 : Beckman Coulter AU5822 (Beckman Coulter, USA) 는화학자동분석기로일반화학검사, 혈청단백질분석, 치료약물농도감시, 약물남용검사등의분야에사용할수있다. AU5822 장비는시간당검사처리율이최대 5,800건이고, 유지보수가간단한특징이있 다. 본연구는일반화학검사 31개항목에대한 AU5822의수행능을평가하고자하였다. 방법 : CLSI 지침에따라 31가지일반화학검사항목에대해정밀도, 직선성, 기존장비와의상관성, 검체간교차오염률을평가하였다. 정밀도평가를위해상품화된정도관리물질인 Lyphochek (Bio-Rad Laboratories Inc, USA), Liquichek (Bio-Rad Laboratories Inc.) 을사용하였고, 직선성평가를위해 Validate (Marine Standard Company, USA) 및환자검체를사용하였다. 기존장비와의상관성평가는환자검체를사용하여 Cobas 8000 modular analyzer (Roche, Switzerland) 와비교하였다. 결과 : 31가지검사항목의총정밀도는저농도와고농도에서모두 5% 이내였고, 모든검사항목은임상적으로중요한범위에서직선성을나타내었다. 기존장비와의상관성평가에서나트륨을제외한 30가지항목모두상관계수 이상으로우수한상관성을나타내었다. 나트륨의상관계수는 이었다. 모든검사항목의검체간교차오염률은 1% 미만이었다. 83

8 결론 : AU5822는 31가지일반화학검사항목측정에있어정밀도, 직선성, 기존장비와의상관성이우수하였고, 검체간교차오염률이낮았다. 또한시간당검사처리율이높고장비내검체이송경로가효율적이므로검사건수가많은검사실의일반화학자동화분석장비로서적합할것으로판단되었다. REFERENCES 1. Lippi G, Dipalo M, Musa R, Avanzini P, Ferrarini C, Pattini A, et al. Evaluation of the analytical performances of the novel Beckman Coulter AU5800. Clin Biochem 2012;45: Lee DH and Yoon KJ. Evaluation of the Dimension Vista 1500 Chemical Autoanalyzer. J Lab Med Qual Assur 2012;34: Clinical and Laboratory Standards Institute. Evaluation of precision performance of quantitative measurement methods; approved guideline. 2nd ed. EP5-A2. Wayne, PA: Clinical and Laboratory Standards Institute, Medicare, Medicaid and CLIA programs; regulations implementing the Clinical Laboratory Improvement Amendments of 1988 (CLIA)--HCFA. Final rule with comment period. Fed Regist 1992;57: Clinical and Laboratory Standards Institute. Evaluation of the linearity of quantitative measurement procedures: A ststistical approach; approved guideline. EP6-A. Wayne, PA: Clinical and Laboratory Standards Institute, Clinical and Laboratory Standards Institute. Method comparison and bias estimation using patient samples; approved guideline. 2nd ed. EP9-A2. Wayne, PA: Clinical and Laboratory Standards Institute, Clinical and Laboratory Standards Institute. Preliminary evalaution of quantitative clinical laboratory methods; approved guideline. 2nd ed. EP10-A2. Wayne, PA: Clinical and Laboratory Standards Institute, Broughton PM. Carry-over in automatic analysers. J Automat Chem 1984;6: Burtis CA, Ashwood ER, et al. eds. Tietz textbook of clinical chemistry and molecular diagnostics. 5th ed. In. St. Louis, Mo.: Elsevier/Saunders, 2012: Yoon KJ, Kim JK, Jang JY. Evaluation of VITROS(R) 5,1 FS automated chemistry analyzer. J Lab Med Qual Assur 2005;27: Ehrmeyer SS, Laessig RH, Leinweber JE, Oryall JJ Medicare/ CLIA final rules for proficiency testing: minimum intralaboratory performance characteristics (CV and bias) needed to pass. Clin chem 1990;36: Westgard JO and Burnett RW. Precision requirements for cost-effective operation of analytical processes. Clin chem 1990;36:

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원저 Lab Med Online Vol. 4, No. 3: 132-139, July 2014 http://dx.doi.org/10.3343/lmo.2014.4.3.132 임상화학 Roche-Hitachi cobas 8000 c702 자동화학분석기의성능평가 Performance Evaluation of the Roche-Hitachi cobas 8000 c702