World J Microbiol Biotechnol DOI 10.1007/s11274-014-1653-9
ORIGINAL PAPER
Comparison of novel and familiar commercial kits for detection of C-reactive protein levels I˙hsan Hakkı Ciftci • Mehmet Koroglu Engin Karakece
•
Received: 27 January 2014 / Accepted: 12 April 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract In this study, randomized patient sera were used to simultaneously evaluate an automated C-reactive protein (CRP) assay and a commercial semi-automated microCRP assay with respect to correlation, linearity, and accuracy. Patient specimens were analyzed; two independent assay runs were performed on i-CHROMA (Boditech Med Inc., Korea) and IMMAGE 800 (Beckman Coulter Inc., USA) analyzers to estimate the between- and withinrun precision. All systems were calibrated, and qualitycontrol materials were analyzed according to the manufacturer’s instructions. The results using the control materials were within the respective manufacturers’ specified limits. The comparison studies were designed using the CLSI EP9-2A guidelines. The mean serum CRP concentrations were 123.2 ± 123.5 mg/L (95 % confidence of interval (CI) 97.9–148.3) using the CRP assay and 130.1 ± 109.3 mg/L (95 % CI 107.9–152.4) using the microCRP assay. The variance values were r = 15,252.6 and 11,935.8 for the CRP and microCRP assays, respectively. The concordance correlation coefficient value was calculated as 0.8314 (95 % CI 0.7594–0.8833). There was a significant correlation between the CRP and microCRP assays: r = 0.8392 and 95 % CI 0.7675–0.8902 (p \ 0.0001). The CRP and microCRP detection methods were well correlated. The i-CHROMA has many advantages over the IMMAGE 800 with respect to space required, analysis time, and system setup/application costs in a laboratory. It may be an attractive instrument for small and intermediate medical centers.
I˙. H. Ciftci M. Koroglu E. Karakece (&) Department of Medical Microbiology, School of Medicine, Sakarya University, Sakarya, Turkey e-mail: [email protected]
Keywords C-reactive protein Immunofluorometric Inflammation
Introduction In the last decade, there has been increasing recognition that inflammatory mechanisms play central roles in the pathogenesis of diseases and their complications. Epidemiological and clinical studies have shown strong and consistent relationships between biomarkers of inflammation and acute events. Inflammation can be detected systemically by measurement of inflammatory markers. Of these markers, C-reactive protein (CRP) has been investigated extensively and has been found to be a stable plasma biomarker for low-grade systemic inflammation. Its levels are upregulated in viral, bacterial, and fungal infections as well as in non-inflammatory conditions (Shaw 1991; Lolekha et al. 2005). CRP is synthesized by the liver in response to interleukin-6 and is well known as a classic acute-phase reactant and as the first acute-phase protein to be described. It is an exquisitely sensitive systemic marker of inflammation and tissue damage. Serum CRP levels may increase from a normal level of \5 to 500 mg/L in a variety of diseases, including immune-mediated conditions, neoplasia, and inflammatory bowel disease, as well as after surgery, while liver failure is the most common cause of a decline in CRP synthesis (Pepys and Hirschfield 2003). Many assays for the detection of CRP have been developed. These include immunochemistry, immunodiffusion, immunofluorometric, and latex agglutination methods. The numbers of published fluoroimmunoassay methods and their applications have increased enormously, and the fluoroimmunoassay has established a position as a reliable analytical method that is used widely, especially in
123
World J Microbiol Biotechnol
serology, microbiology, and virology (Hemmila 1985; Lolekha et al. 2005). Boditech Med Inc. recently developed CRP kit that called microCRPÒ for their semi-automated i-CHROMA system. The i-CHROMA microCRP test is based on fluorescence immunoassay technology and uses a sandwich immunodetection method, such that by mixing detector buffer with a blood specimen in a test vial, the fluorescence-labeled detector anti-CRP antibody in the buffer binds to CRP antigen in the blood specimen. The sample mixture is loaded and migrates on the matrix of the test cartridge; the complexes of detector antibody and CRP are captured as an anti-CRP sandwich pair antibody that is immobilized on the test matrix. In this study, randomized patient sera were used to simultaneously evaluate an automated CRP assay and the above-described new semi-automated microCRP assay with respect to their correlation, linearity, and accuracy.
Materials and methods In this study, routine specimens received by the Education and Research Hospital, Sakarya, Turkey, were analyzed on two analyzers between October 2013 and February 2014. Blood samples were collected into serum tubes (BD SST II yellow top, Grainer, Austria) and were allowed to clot as manufacturer recommendation, 30 min at room temperature before centrifugation (Punyadeera et al. 2011). The randomly selected specimens were analyzed according to the manufacturer’s recommendations on both assays within 4 h of receiving the specimens. All patient specimens were handled anonymously, with traceability only to the barcode/number assigned to the specimen. Quality control materials provided by the respective manufacturers, as well as pooled patient specimens at two levels, were used to evaluate the precision. Two aliquots of quality control material and patient specimens were analyzed per run; two independent assay runs were performed on the i-CHROMA (Boditech Med Inc., Korea) and IMMAGE 800 (Beckman Coulter Inc., USA) analyzers to estimate the between- and within-run precision. All systems were calibrated, and quality control materials were analyzed according to the manufacturers’ instructions. The results of the control materials were within the respective manufacturers’ specified limits. The comparison studies were designed using the CLSI EP9-2A guidelines (NCCLS 2002). Statistical analysis was performed using MedCalc 12.2 (MedCalc Software, Belgium). The level of significance was set at p \ 0.05. The within- and between-batch precision were evaluated using single-factor analysis of
123
variance. Linear regression analysis and Bland–Altman plots were used for analytical comparison.
Results Ninety-six randomized serum samples were evaluated. The IMMAGE 800 and i-CHROMA assays showed linear calibration graphs with a correlation coefficient of r C 0.98 in serial diluted patient sera. Gathered data from the sera in CRP and microCRP assays were not normally distributed. The mean serum CRP concentrations from the CRP and microCRP assays were 123.2 ± 123.5 mg/L (95 % confidence of interval (CI) 97.9–148.3) and 130.1 ± 109.3 mg/L (95 % CI 107.9–152.4) respectively. The variance values were r = 15,252.6 and r = 11,935.8 for the CRP and microCRP assays, respectively. The concordance correlation coefficient value was 0.8314 (95 % CI 0.7594–0.8833). There was a highly significant correlation between the CRP and microCRP assays: r = 0.8392 and 95 % CI 0.7675–0.8902 (p \ 0.0001). The simple linear regression findings show the best-fit data points for all case (R2 = 0.728), and with exclusion of the highest CRP value (R2 = 0.821). Other data are summarized in Table 1. The Bland–Altman difference plot revealed a good correlation. Seven data points were outside the 95 % limits of agreement. The mean difference was –6.9°% points with a 95 % confidence interval of –20.7 to 6.7. Thus, the microCRP assay tended to yield lower results, by –20.7 to 6.7. However, the limits of agreement (–1.96 and 1.96) were sufficient for us to be confident. The limit of agreement between the two methods is shown in the Bland–Altman plot (Fig. 1). Table 1 Evaluation of CRP and microCRP results Variables
CRP
microCRP
Min–max (mg/L)
3.8–660.0
4.4–300.0
Mean (mg/L)
121.2 ± 123.5
130.1 ± 109.3
Variance
15,252.6
11,935.8
95 % Confidence interval for mean
97.9–148.3
107.9–152.4
Interquartile range
146.1
227.5
Concordance correlation coefficient (95 % CI)a
0.8314 (0.7594–0.8833)
Pearson q (precision)b 95 % Confidence interval for r
0.8392 (p \ 0.0001) 0.7675–0.8902
Bias correction factor Cb (accuracy)a
0.9907
Overall meana,b
126.7 ± 47.7
Coefficient of variation (%)a,b
37.6
a a,b
Agreement and responsiveness value for two tests Coefficient of variation from duplicate measurements
World J Microbiol Biotechnol 400
Table 2 Comparison of the main characteristics of IMMAGE 800 and i-CHROMA
300
CRP
microCRP
Instrument
IMMAGE 800 Immunochemistry system (Beckman Coulter, Inc.)
i-CHROMA reader (Boditech Med, Inc.)
Method
Nephelometry
Fluorescence immunoassay
Assay duration (min)
[20
3
Sample volume (lL)
200–300
\10
Measuring range(mg/L)
Initial: 1.0–80.0
2.5–300.0
microCRP
200 +1.96 SD 125,1
100
Mean
0
-7,0 -100
-1.96 SD -139,1
-200 -300 -400 0
100
200
300
400
500
600
CRP Fig. 1 Bland–Altman differences plot for CRP (mg/L) measurements with IMMAGE 800 and microCRP (mg/L) measurements with i-CHROMA. Solid line, mean bias (7 mg/L); dashed lines, 95 % CI (-139.1 to 125.1)
Discussion Factors such as the sample volume, assay analysis time, settled automatic process, measurement range, cost, and quality or traceability of a method may influence a laboratory’s decision to purchase new commercial equipment. In addition, the system setup and application costs are important factors to consider when choosing a CRP assay. On the other hand, ease in handling a system has great importance for laboratory management. The IMMAGE 800 is an automated system and thus has benefits with respect to handling large numbers of samples in larger medical centers. However, the i-CHROMA has great advantages over the IMMAGE 800 with respect to the space required and analysis time, which may make it attractive to small and intermediate medical centers (Harris et al. 1984; Sisman et al. 2007; Zhu et al. 2010). Comparison of the main characteristics of the CRP and microCRP assays (Table 2) highlighted the difference between the sample volume required by the two assays: the IMMAGE 800 uses higher-volume samples (200–300 lL), whereas the i-CHROMA can use low-volume samples (\10 lL). This may be important in a clinical setting, where mainly neonatal specimens are used (fingertip and heel whole-blood samples). The measurement ranges of the two CRP assays also differ; the IMMAGE 800 has a range of 1.0 to 960.0 mg/mL, while the i-CHROMA has a range of 2.5 to 300.0 mg/mL. The concordance correlation coefficient value was 0.8314 (95 % CI 0.7594–0.8833). Furthermore, the CRP and microCRP assays showed a highly significant correlation. However, we speculate that the minimal differences between the two measurements were caused by the detection limits, which especially affected the high CRP values.
Extended: 1.0–960.0
Dilutions
Auto-dilution
Not necessary
Functional assay sensitivity (mg/L)
1.0
2.5
Analytical sensitivity
1.0
1.0
Calibrators
Calibrator 5 plus
Built-in calibration
Traceability
BCR/CAP/IFCC reference material CRM470
BCR/CAP/IFCC reference material CRM470
Serum and plasma (EDTA, Lit-Heparin and SodHeparin)
Whole blood, serum, and EDTA plasma
Specimen type
Another possibility is that the amount of fluorescentlabeled antibody may be less than the CRP level in sera. The discordance in the measurement range may be solved by using an increased conjugate volume in the microCRP assay. The mean difference was –6.9 % with a 95 % confidence interval of –20.7 to 6.0 in the Bland–Altman difference plot. Several possible reasons could explain the differences evident in seven measurements. First, the assays could have been affected by the manual sample preparation process, such as serum transfer on the test cart. Second, the difference in the CRP concentration in sera was higher than that shown by the light scatter/fluorescence analysis, but was not reflected by the i-CHROMA. Third, relatively few clinical samples were used, and the study was conducted using randomized samples from patients whose status was unclear. Finally, all of the discordant results were considered positive by both methods, so none of the patients concerned would have been adversely affected.
Conclusion The CRP and microCRP detection methods were well correlated. The i-CHROMA has considerable advantages
123
World J Microbiol Biotechnol
over the IMMAGE 800 with respect to space required, analysis time, and system setup/application costs in a laboratory, and therefore could be an attractive instrument for small and intermediate medical centers. Acknowledgments This was an experimental, randomized study that evaluated in vitro samples prospectively. No additional samples were taken from patients. Conflict of interest
None.
References Harris RI, Stone PCW, Hudson AG, Stuard J (1984) C reactive protein rapid assay techniques for monitoring resolution of infection in immunosuppressed patients. J Clin Pathol 37:821–828 Hemmila I (1985) Fluoroimmunoassay and immunofluorometric assay. Clin Chem 31(3):359–370
123
Lolekha PH, Chittamma A, Roberts WL, Sritara P, Cheepudomwit S, Suriyawongpaisal P (2005) Comparative study of two automated high-sensitivity C-reactive protein methods in a large population. Clin Biochem 38:31–35 NCCLS (2002) Method comparison and bias estimation using patient samples; approved guideline—second edition. NCCLS document EP9-A2. NCCLS, Wayne. ISBN:1-56238-472-4 Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest. 111:1805–1812 Punyadeera C, Dimeski G, Kostner K, Beyerlein P, Cooper-White J (2011) One-step homogeneous C-reactive protein assay for saliva. J Immunol Methods 373(1):19–25 Shaw AC (1991) Serum C-reactive protein and neopterin concentrations in patients with viral or bacterial infection. J Clin Pathol 44(7):9–596 Sisman AR, Kume T, Tas G, Akan P, Tuncel P (2007) Comparison and evaluation of two C-reactive protein assays based on particleenhanced immunoturbidimetry. J Clin Lab Anal 21:71–76 Zhu X, Duan D, Publicover NG (2010) Magnetic bead based assay for C-reactive protein using quantum-dot fluorescence labeling and immunoaffinity separation. Analyst 135:381–389
ORIGINAL PAPER
Comparison of novel and familiar commercial kits for detection of C-reactive protein levels I˙hsan Hakkı Ciftci • Mehmet Koroglu Engin Karakece
•
Received: 27 January 2014 / Accepted: 12 April 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract In this study, randomized patient sera were used to simultaneously evaluate an automated C-reactive protein (CRP) assay and a commercial semi-automated microCRP assay with respect to correlation, linearity, and accuracy. Patient specimens were analyzed; two independent assay runs were performed on i-CHROMA (Boditech Med Inc., Korea) and IMMAGE 800 (Beckman Coulter Inc., USA) analyzers to estimate the between- and withinrun precision. All systems were calibrated, and qualitycontrol materials were analyzed according to the manufacturer’s instructions. The results using the control materials were within the respective manufacturers’ specified limits. The comparison studies were designed using the CLSI EP9-2A guidelines. The mean serum CRP concentrations were 123.2 ± 123.5 mg/L (95 % confidence of interval (CI) 97.9–148.3) using the CRP assay and 130.1 ± 109.3 mg/L (95 % CI 107.9–152.4) using the microCRP assay. The variance values were r = 15,252.6 and 11,935.8 for the CRP and microCRP assays, respectively. The concordance correlation coefficient value was calculated as 0.8314 (95 % CI 0.7594–0.8833). There was a significant correlation between the CRP and microCRP assays: r = 0.8392 and 95 % CI 0.7675–0.8902 (p \ 0.0001). The CRP and microCRP detection methods were well correlated. The i-CHROMA has many advantages over the IMMAGE 800 with respect to space required, analysis time, and system setup/application costs in a laboratory. It may be an attractive instrument for small and intermediate medical centers.
I˙. H. Ciftci M. Koroglu E. Karakece (&) Department of Medical Microbiology, School of Medicine, Sakarya University, Sakarya, Turkey e-mail: [email protected]
Keywords C-reactive protein Immunofluorometric Inflammation
Introduction In the last decade, there has been increasing recognition that inflammatory mechanisms play central roles in the pathogenesis of diseases and their complications. Epidemiological and clinical studies have shown strong and consistent relationships between biomarkers of inflammation and acute events. Inflammation can be detected systemically by measurement of inflammatory markers. Of these markers, C-reactive protein (CRP) has been investigated extensively and has been found to be a stable plasma biomarker for low-grade systemic inflammation. Its levels are upregulated in viral, bacterial, and fungal infections as well as in non-inflammatory conditions (Shaw 1991; Lolekha et al. 2005). CRP is synthesized by the liver in response to interleukin-6 and is well known as a classic acute-phase reactant and as the first acute-phase protein to be described. It is an exquisitely sensitive systemic marker of inflammation and tissue damage. Serum CRP levels may increase from a normal level of \5 to 500 mg/L in a variety of diseases, including immune-mediated conditions, neoplasia, and inflammatory bowel disease, as well as after surgery, while liver failure is the most common cause of a decline in CRP synthesis (Pepys and Hirschfield 2003). Many assays for the detection of CRP have been developed. These include immunochemistry, immunodiffusion, immunofluorometric, and latex agglutination methods. The numbers of published fluoroimmunoassay methods and their applications have increased enormously, and the fluoroimmunoassay has established a position as a reliable analytical method that is used widely, especially in
123
World J Microbiol Biotechnol
serology, microbiology, and virology (Hemmila 1985; Lolekha et al. 2005). Boditech Med Inc. recently developed CRP kit that called microCRPÒ for their semi-automated i-CHROMA system. The i-CHROMA microCRP test is based on fluorescence immunoassay technology and uses a sandwich immunodetection method, such that by mixing detector buffer with a blood specimen in a test vial, the fluorescence-labeled detector anti-CRP antibody in the buffer binds to CRP antigen in the blood specimen. The sample mixture is loaded and migrates on the matrix of the test cartridge; the complexes of detector antibody and CRP are captured as an anti-CRP sandwich pair antibody that is immobilized on the test matrix. In this study, randomized patient sera were used to simultaneously evaluate an automated CRP assay and the above-described new semi-automated microCRP assay with respect to their correlation, linearity, and accuracy.
Materials and methods In this study, routine specimens received by the Education and Research Hospital, Sakarya, Turkey, were analyzed on two analyzers between October 2013 and February 2014. Blood samples were collected into serum tubes (BD SST II yellow top, Grainer, Austria) and were allowed to clot as manufacturer recommendation, 30 min at room temperature before centrifugation (Punyadeera et al. 2011). The randomly selected specimens were analyzed according to the manufacturer’s recommendations on both assays within 4 h of receiving the specimens. All patient specimens were handled anonymously, with traceability only to the barcode/number assigned to the specimen. Quality control materials provided by the respective manufacturers, as well as pooled patient specimens at two levels, were used to evaluate the precision. Two aliquots of quality control material and patient specimens were analyzed per run; two independent assay runs were performed on the i-CHROMA (Boditech Med Inc., Korea) and IMMAGE 800 (Beckman Coulter Inc., USA) analyzers to estimate the between- and within-run precision. All systems were calibrated, and quality control materials were analyzed according to the manufacturers’ instructions. The results of the control materials were within the respective manufacturers’ specified limits. The comparison studies were designed using the CLSI EP9-2A guidelines (NCCLS 2002). Statistical analysis was performed using MedCalc 12.2 (MedCalc Software, Belgium). The level of significance was set at p \ 0.05. The within- and between-batch precision were evaluated using single-factor analysis of
123
variance. Linear regression analysis and Bland–Altman plots were used for analytical comparison.
Results Ninety-six randomized serum samples were evaluated. The IMMAGE 800 and i-CHROMA assays showed linear calibration graphs with a correlation coefficient of r C 0.98 in serial diluted patient sera. Gathered data from the sera in CRP and microCRP assays were not normally distributed. The mean serum CRP concentrations from the CRP and microCRP assays were 123.2 ± 123.5 mg/L (95 % confidence of interval (CI) 97.9–148.3) and 130.1 ± 109.3 mg/L (95 % CI 107.9–152.4) respectively. The variance values were r = 15,252.6 and r = 11,935.8 for the CRP and microCRP assays, respectively. The concordance correlation coefficient value was 0.8314 (95 % CI 0.7594–0.8833). There was a highly significant correlation between the CRP and microCRP assays: r = 0.8392 and 95 % CI 0.7675–0.8902 (p \ 0.0001). The simple linear regression findings show the best-fit data points for all case (R2 = 0.728), and with exclusion of the highest CRP value (R2 = 0.821). Other data are summarized in Table 1. The Bland–Altman difference plot revealed a good correlation. Seven data points were outside the 95 % limits of agreement. The mean difference was –6.9°% points with a 95 % confidence interval of –20.7 to 6.7. Thus, the microCRP assay tended to yield lower results, by –20.7 to 6.7. However, the limits of agreement (–1.96 and 1.96) were sufficient for us to be confident. The limit of agreement between the two methods is shown in the Bland–Altman plot (Fig. 1). Table 1 Evaluation of CRP and microCRP results Variables
CRP
microCRP
Min–max (mg/L)
3.8–660.0
4.4–300.0
Mean (mg/L)
121.2 ± 123.5
130.1 ± 109.3
Variance
15,252.6
11,935.8
95 % Confidence interval for mean
97.9–148.3
107.9–152.4
Interquartile range
146.1
227.5
Concordance correlation coefficient (95 % CI)a
0.8314 (0.7594–0.8833)
Pearson q (precision)b 95 % Confidence interval for r
0.8392 (p \ 0.0001) 0.7675–0.8902
Bias correction factor Cb (accuracy)a
0.9907
Overall meana,b
126.7 ± 47.7
Coefficient of variation (%)a,b
37.6
a a,b
Agreement and responsiveness value for two tests Coefficient of variation from duplicate measurements
World J Microbiol Biotechnol 400
Table 2 Comparison of the main characteristics of IMMAGE 800 and i-CHROMA
300
CRP
microCRP
Instrument
IMMAGE 800 Immunochemistry system (Beckman Coulter, Inc.)
i-CHROMA reader (Boditech Med, Inc.)
Method
Nephelometry
Fluorescence immunoassay
Assay duration (min)
[20
3
Sample volume (lL)
200–300
\10
Measuring range(mg/L)
Initial: 1.0–80.0
2.5–300.0
microCRP
200 +1.96 SD 125,1
100
Mean
0
-7,0 -100
-1.96 SD -139,1
-200 -300 -400 0
100
200
300
400
500
600
CRP Fig. 1 Bland–Altman differences plot for CRP (mg/L) measurements with IMMAGE 800 and microCRP (mg/L) measurements with i-CHROMA. Solid line, mean bias (7 mg/L); dashed lines, 95 % CI (-139.1 to 125.1)
Discussion Factors such as the sample volume, assay analysis time, settled automatic process, measurement range, cost, and quality or traceability of a method may influence a laboratory’s decision to purchase new commercial equipment. In addition, the system setup and application costs are important factors to consider when choosing a CRP assay. On the other hand, ease in handling a system has great importance for laboratory management. The IMMAGE 800 is an automated system and thus has benefits with respect to handling large numbers of samples in larger medical centers. However, the i-CHROMA has great advantages over the IMMAGE 800 with respect to the space required and analysis time, which may make it attractive to small and intermediate medical centers (Harris et al. 1984; Sisman et al. 2007; Zhu et al. 2010). Comparison of the main characteristics of the CRP and microCRP assays (Table 2) highlighted the difference between the sample volume required by the two assays: the IMMAGE 800 uses higher-volume samples (200–300 lL), whereas the i-CHROMA can use low-volume samples (\10 lL). This may be important in a clinical setting, where mainly neonatal specimens are used (fingertip and heel whole-blood samples). The measurement ranges of the two CRP assays also differ; the IMMAGE 800 has a range of 1.0 to 960.0 mg/mL, while the i-CHROMA has a range of 2.5 to 300.0 mg/mL. The concordance correlation coefficient value was 0.8314 (95 % CI 0.7594–0.8833). Furthermore, the CRP and microCRP assays showed a highly significant correlation. However, we speculate that the minimal differences between the two measurements were caused by the detection limits, which especially affected the high CRP values.
Extended: 1.0–960.0
Dilutions
Auto-dilution
Not necessary
Functional assay sensitivity (mg/L)
1.0
2.5
Analytical sensitivity
1.0
1.0
Calibrators
Calibrator 5 plus
Built-in calibration
Traceability
BCR/CAP/IFCC reference material CRM470
BCR/CAP/IFCC reference material CRM470
Serum and plasma (EDTA, Lit-Heparin and SodHeparin)
Whole blood, serum, and EDTA plasma
Specimen type
Another possibility is that the amount of fluorescentlabeled antibody may be less than the CRP level in sera. The discordance in the measurement range may be solved by using an increased conjugate volume in the microCRP assay. The mean difference was –6.9 % with a 95 % confidence interval of –20.7 to 6.0 in the Bland–Altman difference plot. Several possible reasons could explain the differences evident in seven measurements. First, the assays could have been affected by the manual sample preparation process, such as serum transfer on the test cart. Second, the difference in the CRP concentration in sera was higher than that shown by the light scatter/fluorescence analysis, but was not reflected by the i-CHROMA. Third, relatively few clinical samples were used, and the study was conducted using randomized samples from patients whose status was unclear. Finally, all of the discordant results were considered positive by both methods, so none of the patients concerned would have been adversely affected.
Conclusion The CRP and microCRP detection methods were well correlated. The i-CHROMA has considerable advantages
123
World J Microbiol Biotechnol
over the IMMAGE 800 with respect to space required, analysis time, and system setup/application costs in a laboratory, and therefore could be an attractive instrument for small and intermediate medical centers. Acknowledgments This was an experimental, randomized study that evaluated in vitro samples prospectively. No additional samples were taken from patients. Conflict of interest
None.
References Harris RI, Stone PCW, Hudson AG, Stuard J (1984) C reactive protein rapid assay techniques for monitoring resolution of infection in immunosuppressed patients. J Clin Pathol 37:821–828 Hemmila I (1985) Fluoroimmunoassay and immunofluorometric assay. Clin Chem 31(3):359–370
123
Lolekha PH, Chittamma A, Roberts WL, Sritara P, Cheepudomwit S, Suriyawongpaisal P (2005) Comparative study of two automated high-sensitivity C-reactive protein methods in a large population. Clin Biochem 38:31–35 NCCLS (2002) Method comparison and bias estimation using patient samples; approved guideline—second edition. NCCLS document EP9-A2. NCCLS, Wayne. ISBN:1-56238-472-4 Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest. 111:1805–1812 Punyadeera C, Dimeski G, Kostner K, Beyerlein P, Cooper-White J (2011) One-step homogeneous C-reactive protein assay for saliva. J Immunol Methods 373(1):19–25 Shaw AC (1991) Serum C-reactive protein and neopterin concentrations in patients with viral or bacterial infection. J Clin Pathol 44(7):9–596 Sisman AR, Kume T, Tas G, Akan P, Tuncel P (2007) Comparison and evaluation of two C-reactive protein assays based on particleenhanced immunoturbidimetry. J Clin Lab Anal 21:71–76 Zhu X, Duan D, Publicover NG (2010) Magnetic bead based assay for C-reactive protein using quantum-dot fluorescence labeling and immunoaffinity separation. Analyst 135:381–389
