원저 Lab Med Online Vol. 4, No. 3: , July 임상화학 Roche-Hitachi cobas 8000 c702 자동화학분석기의성능평가 Perform

Size: px

Start display at page:

Download "원저 Lab Med Online Vol. 4, No. 3: , July 임상화학 Roche-Hitachi cobas 8000 c702 자동화학분석기의성능평가 Perform"

혜라 임
5 years ago
Views:

D. 1, Tae-Dong Jeong, M.D. 2, Woochang Lee, M.D. 2, Sail Chun, M.D. 2, Won-Ki Min, M.D. 2 가톨릭대학교의과대학진단검사의학교실 1, 울산대학교의과대학서울아산병원진단검사의학과 2 Department of Laboratory Medicine 1, College of Medicine, The

requires specific technical solutions such as open, flexible, and adaptable space, suitable equipment requirements, and laboratory instrumentation that combine excellent analytical performance with a

1 원저 Lab Med Online Vol. 4, No. 3: , July 임상화학 Roche-Hitachi cobas 8000 c702 자동화학분석기의성능평가 Performance Evaluation of the Roche-Hitachi cobas 8000 c702 Chemistry Autoanalyzer 김소영 1 정태동 2 이우창 2 전사일 2 민원기 2 So-Young Kim, M.D. 1, Tae-Dong Jeong, M.D. 2, Woochang Lee, M.D. 2, Sail Chun, M.D. 2, Won-Ki Min, M.D. 2 가톨릭대학교의과대학진단검사의학교실 1, 울산대학교의과대학서울아산병원진단검사의학과 2 Department of Laboratory Medicine 1, College of Medicine, The Catholic University of Korea, Seoul; Department of Laboratory Medicine 2, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea Background: Optimal operational efficiency requires specific technical solutions such as open, flexible, and adaptable space, suitable equipment requirements, and laboratory instrumentation that combine excellent analytical performance with a capacity for testing large panels in a high throughput manner, under rapid turnaround times. Thus, the aim of this study was to assess the analytical performance of the novel Roche- Hitachi cobas 8000 c702 Chemistry Autoanalyzer. Methods: Precision, linearity, carry over, detection limits, and comparison studies were performed with 31 routine clinical chemistry tests according to the CLSI guidelines. Commercial quality chemistry control material (Lyphochek, Bio-Rad, USA) and patient sera were used as the test specimens. Unicel DxC instrument (Beckman Coulter, USA) was used as a control analyzer to evaluate the correlation. Results: The total coefficients of variations (CVs) of almost all the analytes were between 0.4 and 4.1%, except for CO2 and ammonia. Excellent linearities were observed in the performance ranges used (r>0.99, slope, ). Correlations with analogous tests ran on the Unicel DxC instrument were good, correlation coefficients ranging between and The carryover ranged from to 0.481%. Conclusions: The Roche-Hitachi cobas 8000 c702 Chemistry Autoanalyzer showed satisfactory precision, linearity, carry over, detection limits, and high throughput capacity. The instrument performance correlated well with the Unicel DxC analyzer. We conclude that the balance of elevated throughput and optimal analytical performance should make Roche-Hitachi cobas c702 Chemistry Autoanalyzer suitable for very large clinical laboratories. Key Words: Analytical performance, Roche-Hitachi cobas 8000 c702, Evaluation 서론 일반화학검사의업무는대부분자동화학분석기를통해이루어 Corresponding author: Won-Ki Min 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: , wkmin@amc.seoul.kr Received: May 21, 2013 Revision received: October 18, 2013 Accepted: November 18, 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. 진다. 1960년대부터화학분석기가임상검사실에도입되기시작하면서많은항목의검사를수행할수있는자동화학분석기들이지속적으로개발되어왔고최근에는화학분석기에있어서도검사비의절감과동시에신속, 정확한검사결과의보고에대한요구도와관심이증가하고있다 [1]. 현재의자동화학분석기의주된목표는임상요구에대한적합성, 검사비용의절감및정도관리능력의향상이라고볼수있다. 또한, 검사기기의통합이검사기기의분배에따른검체량, 검사비용, 검사인원및검사소요시간의증대등의문제점을부분적으로해결하여효율적인검사환경을구축하는데큰영향을미친다고볼수있다 [2]. 이러한상황에서각검사실마다새로운기기를도입할경우도입에앞서검사기기의유용성과분석능력을평가하는작업이필요하며, 검사실마다자동화학분석기의도입시에는적절한사전평가를거친후사용하는것이신뢰성있는결과를얻는데중요하다 [3-6]. 최근 Roche Diagnostic System 사 eissn

2 에서개발되어국내에소개된 cobas 8000 C702 (Roche Diagnostics System, Switzerland) 는 cobas modular platform 으로출시된 Serum Work Area (SWA) 솔루션이다. 임상화학검사를수행하는 c702 과 c502 모듈을조합하여시간당최대 8,400 테스트가가능하도록디자인되었다. 특히, 검사중에도시약장착이가능하고, 병목현상없는검체이송을가능하게하는 track 및 Module Sample Buffer (MSB) 는검사실의효율성을극대화시킬수있을것으로기대한다. 그러나, 아직까지 cobas 8000의 c702 모듈에대한임상화학검사의성능평가를제시한연구가없어임상화학검사에적용하는데참고할자료가부족한실정이다. 이연구를통해 cobas 8000 c702 모듈에대한대규모성능평가를해보고자한다. 대상및방법 1. 대상 2012년 6월 1개월간본원임상화학검사실에도입된 Cobas 8000 c702 기기의성능을분석하였다. 임상화학검사 31항목 (albumin, alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST], blood urea nitrogen [BUN], calcium [Ca], cholesterol, creatinine, γ-glutamyl tranferase [γ-gt], glucose, phosphorus, total bilirubin, triglyceride [TG], total protein, uric acid, creatine kinase [CK], direct bilirubin, iron [Fe], high density lipoprotein cholesterol [HDL-cholesterol], lactate dehydrogenase [LD], magnesium [Mg], chloride [Cl], potassium [K], sodium [Na], ammonia, CO 2, high sensitive c-reactive protein [hs-crp]) 에대하여정밀도, 직선성, 측정한계, 상관성을평가하였고, 상관성평가는 Unicel DxC (Beckman Coulter, USA) 에대한관계를분석하였다. 검체간교차오염률은제한적으로 8항목 (LDL-cholesterol, hs-crp, AST, ALT, iron, lipase, CK, and LD) 에대하서만실시하였다. 검체로는상품화된정도관리물질인 Lyphocheck Level I과 Level II (Bio- Rad, CA, USA) 과, 서울아산병원에내원한환자들의혈청검체를이용하였는데, 이는임상화학검사를의뢰한환자들의혈청검체로서정상영역, 높은값, 낮은값을갖는 60명의환자의검체를상관성평가에사용하였다. 2. 방법 1) 정밀도평가상품화된정도관리물질인 Lyphocheck (Bio-Rad, CA, USA) Level I, II를사용하였으며, 검사항목에따라 Level I, II의농도는다르게분포하였다. 총 31개검사항목에대하여검사중정밀도 (within-run precision), 검사간정밀도 (between run precision), 검사일간정밀도 (between day precision) 와총정밀도 (total precision) 를평가하였다. 각각의물질은하루에오전, 오후두번측정하여 National Committee for Laboratory Standards (CLSI) EP5-A2 에제시된방법에따라정밀도를평가하였다 [7]. 2) 직선성평가직선성평가물질 Validate (Maine Standards Company, LLC, ME, USA) 를이용하여 CLSI EP 6-A protocol 에서제시한방법에따라직선성을평가하였다 [8]. CLSI EP 6-A2에따라 Validate (Maine Standards Company, LLC, ME, USA) 5단계농도를준비하여각각에대하여 4회씩반복측정하여구한평균치로부터회귀직선식을구하였다 [9]. 직선성의평가는 Allowable systemic error 범위에속하는것을유효한것으로판단하였다. 3) 상관성평가상관관계는 CLSI EP 9-A에따라정상영역, 높은값, 낮은값을갖는환자의검체가골고루포함되도록하여각검사항목별로 60 검체씩수집하여각각의검체를 Cobas 8000 c702 (Roche Diagnostics System, Switzerland) 와 Unicel DxC (Beckman Coulter, USA) 두기기로각각측정하여분석한후그결과에대해상관성평가를실시하였다. 각장비에서 2회반복측정한값의평균값으로회귀방정식과상관계수 (coefficient of correlation, r) 를산출하였다. 상관계수가 이상이면상관성이우수하다고판단하였고, 경우에따라 CLIA88의허용범위를참고하여판단하였다 [10]. 4) 검체간교차오염률평가검체간교차오염률은 8종목을대상으로평가하였다. 상품화된정도관리물질인 Lyphocheck Level I과 Level II을사용하였다. 고농도물질 (H1, H2, H3, H4) 을 4번연속측정한후저농도물질 (L1, L2, L3, L4) 을 4번연속측정하였고, {L1-(L3+L4)/2 100}/{(H3+H2)/2- (L3+L4)/2} 으로교차오염률을구하였다. 5) 측정한계평가 CLSI EP17-A 에준하여, limit of blank (LoB) 와 limit of detection (LoD) 을분석하였다. LoB는 O(zero)level calibrator, negative sample, 환자검체중가장낮은농도의검체를사용하여, LoB =mean blank (SD blank) 으로구하였다 [10]. LoD는최저농도 calibrator의 dilution sample, 환자검체중낮은농도의 sample을사용하여 LoD =LoB (SD low concentration sample) 으로구하였다. 6) 통계분석통계분석에는 EP evaluator Release 10 (David G. Rhoads Assoc.,

3 Table 1. Precision of the Roche-Hitachi cobas 8000 c702 Chemistry Autoanalyzer Test item QC Mean SD cobas cobas Total CV Within-run Between-run Between-day Total Mean SD CV Within-run Between-run Between-day Total Mean SD CV CA Level Level Glu Level Level CREA Level Level UA Level Level CHOL Level Level TP Level Level ALB Level Level AST Level Level ALT Level Level ALP Level Level TB Level Level P Level Level BUN Level Level GGT Level Level DB Level Level Na Level Level K Level Level Cl Level Level CO2 Level Level MG Level Level AMY Level Level LIP Level Level CK Level Level (Continued to the next page)

4 Table 1. Continued Test item QC Mean SD cobas cobas Total CV Within-run Between-run Between-day Total Mean SD CV Within-run Between-run Between-day Total Mean SD CV LD Level Level IRON Level Level TIBC Level Level TG Level Level HDL Level Level LDL Level Level AMM Level Level Level CRP Level CRP hs Level Level Level Level Level Kennett square, PA, USA) 과 SPSS 12.0 (SPSS Inc., Chicago, IL, USA) 를이용하였다. 과상관계수 (r) 는모두 이상으로측정되어모두우수하거나 양호한상관성을보여주었다 (Table 3). 결과 1. 정밀도 31개항목의검사차례내정밀도와총정밀도는 Table 1과같다. 총정밀도는 CO 2 와 ammonia를제외한모든항목에서정밀도 5.0% 이내였다. CO 2 의총정밀도는 Bio-Rad Level II에서각각 5.39%, 5.28% 였고, ammonia는 Bio-Rad Level I에서의총정밀도가 10.98%, 10.18% 였다 (Table 1). 4. 검체간교차오염률검체간교차오염률은측정한 8개항목에서 % 로측정되었다 (Table 4). 5. 측정한계 31개검사항목의 LoB와 LoD는 Table 5에기술하였다. 고찰 2. 직선성직선성평가를위한단계별물질에서기대치와직선성을확인한결과, 모든검사항목에대하여임상적으로의미있는범위에서 %error가모두 allowable error 범위내로분석되어직선성이유효한것으로평가되었다 (Table 2). 3. 상관성기존시약과의항목별측정치에대한회귀분석의기울기, 절편 일반화학검사는질환의진단에기본적인지표를제공해주는중요한검사이며신뢰성있는검사를제공하기위해서는새로운검사기기를검사실에도입하고자할때에일상검사에사용하기전에그기기에대한정확한평가를선행하여야한다. 저자들은최근국내에도입된임상화학검사기기인 cobas 8000 c702 를평가하였다. CLSI guideline 에서제시한대로정밀도, 직선성을평가하였고, 기존임상화학검사기기인 Unicel DxC와의상관성을평가하였다. CLSI guideline에따르면정밀도평가는일간정밀도가총정밀

5 Table 2. Linearity of the Roche-Hitachi cobas 8000 c702 Chemistry Autoanalyzer Item Ranges cobas cobas Allowable Linear regression analysis Linear regression analysis % error systemic error (%) Ranges Slope Intercept Slope Intercept % error Allowable systemic error (%) CA Glu CREA UA CHOL TP ALB AST ALT ALP TB P BUN GGT DB Na K Cl CO MG AMY LIP CK LD IRON TIBC TG HDL LDL AMM CRP CRP hs 도의큰구성요소이므로평가는충분히긴기간동안실시되어야하며최소한 20일이상반복측정하는것이필요하고, single run으로검사중정밀도를평가하는것은평상시의검사작업의요소를반영하지못할수있다고하였다. 이에 CLSI 기준을따라 20일간반복측정하였으며저농도와고농도의정도관리물질을이용하여검사중변이계수와총변이계수를구하여정밀도평가를실시하였다. 같은항목의검사중과총표준편차혹은변이계수는저농도와고농도의정도관리물질간에큰차이를보이지않았으며변이계수는 CO 2 와암모니아를제외한모든종목에서 5% 미만으로양호한결과를보였다. CO 2 의변이계수가 level II (mean, ) 에서 5.39%, 5.28% 였으나, level I (mean, ) 에서는모두 5% 이하로허용범위를만족하는값이었다. 암모니아의경우도 (mean, 29.13) 정도관리물질의 total CV가두기기에서 10.98, 9.38 로각각분석되었으나이는검사항목들의낮은농도로인하여소량의편차가변이계수산출에큰영향을미친것으로판단되었다 [11]. 검사일간정밀도는검사일내정밀도보다변이계수가약간큰값을나타내었으며이는다른기기의분석보고와같은결과를보였다 [5, 6]. 직선성을평가하기위하여직선성평가물질을사용하였고, 단계별기대치와직선성을확인한결과모든항목에대하여임상적으로측정가능한농도범위내에서 %error가 allowable systemic error 범위내로분석되어매우우수한직선성을보였다. 상관성평가는정상과비정상측정치를모두포함하도록넓은범위의농도의환자검체를선택하여상관관계를분석하였다. 대부분이항목에서 CLSI 권고기준인 이상의상관계수 (r) 를만족

6 Table 3. Correlation of the Roche-Hitachi cobas 8000 c702 Chemistry Autoanalyzer Test item N cobas cobas Deming regression Deming regression Mean bias r N Slope Intercept Slope Intercept Mean bias CA Glu CREA UA CHOL TP ALB AST ALT ALP TB P BUN GGT DB Na K Cl CO MG AMY LIP CK LD IRON TIBC TG HDL LDL AMM CRP CRP hs r Table 4. Carryover of the Roche-Hitachi cobas 8000 c702 Chemistry Autoanalyzer Test item cobas (%) cobas (%) AST ALT LIP CK LD IRON LDL CRP hs 하여높은상관성을보였다. Cobas 1 기기의 Chloride 는 r=0.9709, cobas 2 기기의 LD 는 r= 로 와근소한차이를보였고, ammonia 는두기기모두 r=0.9219, 로다른검사항목에비 해약간낮은상관계수값을갖지만, CLIA 88의 criteria for acceptable performance를대입하여계산된 EP evaluator 의분석결과상관성이양호한것으로판단되므로임상적으로문제가되지않을것으로보인다. 교차오염률검증결과 % 의수치를보여검체간의교차오염도는매우낮다고판정할수있었다. 결론적으로 Cobas 8000 c702 는우수한정밀도와직선성, 교차오염률을나타내었으며, 기존의검사기기인 Unixel DxC와우수한상관성을보여기기성능이만족할만하였다. 또한검사업무의신속화, 효율화를도모하여검사실의업무흐름을개선할수있으므로검사건수가많은대형병원검사실에서정확하고빠른검사결과를낼수있을것으로판단된다. 따라서, 본기기는검사의효율화와정확성을도모할수있으므

7 Table 5. Detection limits of the Roche-Hitachi cobas 8000 c702 Chemistry Autoanalyzer Test item Unit cobas cobas LoB LoD LoB LoD CA mg/dl Glu mg/dl CREA mg/dl UA mg/dl CHOL mg/dl TP g/dl ALB g/dl AST U/L ALT U/L ALP U/L TB mg/dl P mg/dl BUN mg/dl GGT U/L DB mg/dl Na mmol/l K mmol/l Cl mmol/l CO2 mmol/l MG mg/dl AMY U/L LIP U/L CK U/L LD U/L IRON μg/dl TIBC μg/dl TG mg/dl HDL mg/dl LDL mg/dl AMM μg/dl CRP mg/dl CRP hs mg/dl 로, 검사건수가많은대형병원검사실에유용하게사용될수있을 것임을입증할수있었다. 요약 배경 : 최근 Roche-Hitachi 사의 cobas 8000 c702 는화학과면역검사 를통합할수있는최신시스템이다. 저자들은상기장비의사용시 생길수있는시행착오를예방하고신뢰성있는결과를얻기위해 상기장비의유용성과분석능력을평가하고자하였다. 방법 : 일반화학 31 검사항목에대해정밀도, 직선성, 검체간오염 률과기존장비와의상관성을 CLSI 지침에따라평가하였다. 정밀 도평가를위해상품화된정도관리물질인 Lyphocheck (Bio-Rad Laboratories Inc., USA) Level I, II 를사용하였고, 직선성평가를위 해 Validate (Marine Standard Company, USA) 를사용하였다. 기존장비 Unicel DxC (Beckman Coulter, USA) 와의상관성평가에는환자검체를사용하였다. 결과 : 일반화학 31 검사항목중 CO 2 와 ammonia를제외한검사종목의총정밀도는 % 였고, 모든검사항목은임상적으로중요한범위에서직선성을나타내었다. Unicel DxC와의상관성은상관계수 으로우수하였고, 검체간교차오염률은 % 였다. 결론 : Roche-Hitachi 사의 cobas 8000 c702 는일반화학검사항목의측정에서우수한정밀도, 직선성, 기존장비와의상관성을보여주었고, 검체간교차오염률도낮아기기성능이만족할만하였다. 결론적으로, 본기기는검사의효율화와정확성을도모할수있으므로, 검사건수가많은대형병원검사실에유용하게사용될수있을것임을입증할수있었다. REFERENCES 1. Brombacher PJ, Marell GJ, Westerhuis LW. Laboratory workflow analysis and introduction of a multifunctional analyzer. Eur J Clin Biochem 1996;34: Vap LM and Mitzner B. An update on chemistry analyzers [Review]. The Veterinary Clinics of North America Small Animal Practice 1996; 26: Park SS, Ma SJ, Maeng KY. Evaluation of automated chemistry analyzer: Chem 1. J Lab Med Qual Assur 1989;11: Park JS, Chun S, Min WK. Evaluation of automated chemistry analyzer Synchron LX20. Korean J Clin Pathol 2000;20: Kim MY and Ha KI. Evaluation of automated chemistry analyzer ISP J Lab Med Qual Assur 1997;18: Kim JQ. Evaluation of automated chemistry analyzer Cobas Bio. J Lab Med Qual Assur 1984;6: Clinical and Laboratory Standards Institute. Evaluation of precision performance of quantitative measurement methods; approved guideline. 2nd ed. NCLSI document EP5-A2. Wayne PA: Clinical and Laboratory Standards Institute, Clinical and Laboratory Standards Institute. Evaluation of linearity of quantitative measurement procedures; a statistical approach. 2nd ed. CLSI document 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. CLSI document EP9-A2. Wayne PA: Clinical and Laboratory Standards

8 Institute, Clinical and Laboratory Standards Institute. Protocols for determination of limits of detection and limits of quantification; approved guideline. CLSI document EP17-A. Wayne PA: Clinical and Laboratory Standards Institute, Cho SE, Nam JW, Hong KS. Performance Evaluation of the Hitachi Chemistry Autoanalyzer. Korean J Clin Pathol 2001;21:

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

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