Please only refer to the current product lot insert enclosed with the kits package for execution

and reporting

0123 130206014M: 100 tests

130606014M: 050 tests

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MAGLUMI hs-cTnI (CLIA)
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INTENDED USE
The kit is an in vitro chemiluminescence immunoassay for the quantitative determination of cardiac Troponin I (cTnI) in human
serum and plasma using the MAGLUMI series Fully-auto chemiluminescence immunoassay analyzer (including Maglumi 600,
Maglumi 800, Maglumi 1000, Maglumi 2000, Maglumi 2000 Plus, Maglumi 4000 and Maglumi 4000 Plus).
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SUMMARY AND EXPLANATION OF THE TEST

Cardiac troponin I, often denoted as cTnI, is presented in cardiac muscle tissue by a single isoform with molecular weight 23.9
kDa and it consists of 209 amino acid residues. Troponin I is a part of the troponin protein complex, where it binds to actin in thin
myofilaments to hold the actin-tropomyosin complex in place. Because of it, myosin cannot bind actin in relaxed muscle. When
calcium binds to the troponin C it causes conformational changes which lead to dislocation of troponin I and finally tropomyosin
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1-3
leaves the binding site for myosin on actin leading to contraction of muscle .
cTnI differs from other troponins due to its N-terminal extension of 26 amino acids. This extension contains two serines, residues
23 and 24, which are phosphorylated by protein kinase A in response to beta-adrenergic stimulation and important in increasing
4
the inotropic response . Phosphorylation of cTnI changes the conformation of the protein and modifies its interaction with other
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troponins as well as the interaction with anti-TnI antibodies. These changes alter the myofilament response to calcium, and are of
interest in targeting heart failure. Multiple reaction monitoring of human cTnI has revealed that there are 14 phosphorylation sites
4,5
and the pattern of phosphorylation observed these sites is changed in response to disease .
cTnI is a contractile protein that is released into the circulation after myocardial cell injury. cTnI remains elevated for 7 to 10 days
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after release into circulation, which may allow screening at a single postoperative time point to identify patients who had
myocardial injury. Unlike creatine kinase and its MB isoenzyme (CK-MB), cTnI is not found in skeletal muscle and is therefore a
highly sensitive and specific for myocardial necrosis. For more than 15 years cTnI has been known as a reliable marker of
cardiac muscle tissue injury. It is considered to be more sensitive and significantly more specific in diagnosis of the myocardial
infarction than the "golden marker" of last decades – CK-MB, as well as total creatine kinase, myoglobin and lactate
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6-9
dehydrogenase isoenzymes. During surgery, cTnI is reported to be more specific for diagnosis of MI than CK-MB . In patients
with acute coronary syndromes, elevated cTnI levels at the onset of symptoms are associated with an increased risk of cardiac
morbidity and mortality, and cTnI has been shown to be a useful tool for risk stratification in emergency room and inpatient
10-12
settings .

PRINCIPLE OF THE TEST

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The hs-cTnI assay is a sandwich chemiluminescence immunoassay.

The sample (or calibrator/control, if applicable), anti-cTnI monoclonal antibody-labeled ABEI and magnetic microbeads coated
with another anti-cTnI monoclonal antibody are mixed thoroughly and incubated at 37°C, forming sandwich of
immuno-complexes. After precipitation in a magnetic field, the supernatant is decanted and then a wash cycles is performed.
Subsequently, the Starter 1+2 are added to initiate a chemiluminescent reaction. The light signal is measured by a photomultiplier
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within 3 seconds as relative light units (RLUs), which is proportional to the concentration of cTnI present in the sample (or
calibrator/control, if applicable).

KIT COMPONENTS
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Material provided
100 tests 50 tests
Components Contents
(REF: 130206014M) (REF: 130606014M)
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Coated with anti-cTnI monoclonal antibody, NaN3

Magnetic Microbeads 2.5 mL 2.0 mL
(<0.1%).
Calibrator Low cTnI antigen, bovine serum, NaN3 (<0.1%). 3.0 mL 2.0 mL
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Calibrator High cTnI antigen, bovine serum, NaN3 (<0.1%). 3.0 mL 2.0 mL
Wash Buffer Containing Tween-20 and NaN3 (<0.1%). 22.5 mL 12.5 mL
Anti-cTnI monoclonal antibody labeled ABEI,
ABEI Label 12.5 mL 7.5 mL
containing BSA, NaN3 (<0.1%).

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Control 1 cTnI antigen, bovine serum, NaN3 (<0.1%). 2.0 mL 2.0 mL

Control 2 cTnI antigen, bovine serum, NaN3 (<0.1%). 2.0 mL 2.0 mL
All reagents are provided ready-to-use.

Accessories Required But Not Provided

MAGLUMI Series:
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Reaction Module REF: 630003
Starter 1+2 REF: 130299004M
Wash Concentrate REF: 130299005M
Light Check REF: 130299006M
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Please order accessories from Shenzhen New Industries Biomedical Engineering Co., Ltd. (SNIBE) or our authorized
representatives.

CALIBRATION
Traceability: This method has been standardized against the NIST SRM 2921.
Test of assay specific calibrators allows the RLU values to adjust the assigned master curve. Results are determined via a
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calibration curve which is instrument-specifically generated by 2-point calibration and a master curve (10 calibrations) provided
via the reagent Radio Frequency Identification (RFID) CHIP.
Recalibration is recommended if any of the following conditions occurs:
 After each exchange of lots (Reagent or Starter 1+2).
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 Every week and/or each time a new reagent kit is used (recommended).

 After instrument service is required.

 If controls lie outside the expected range.

 Whenever room temperature changes exceed 5° C (recommended).

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QUALITY CONTROL
Follow government regulations or accreditation requirements for quality control frequency.
Internal quality control is only applicable with MAGLUMI system. For instructions for use and target value refer to hs-cTnI (CLIA)
Quality Control Information. User needs to judge results with their own standards and knowledge.
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For detailed information about entering quality control values, refer to operating instructions of MAGLUMI series Fully-auto
chemiluminescence immunoassay analyzer.
To monitor system performance and chart trends, commercially available quality control materials are required. Treat all quality
control samples the same as patient samples. A satisfactory level of performance is achieved when analyte values obtained are
within the acceptable Control Range for the system or within your range, as determined by an appropriate internal laboratory
quality control scheme. If the quality control results do not fall within the Expected Values or within the laboratory’s established
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values, do not report results. Take the following actions:

 Verify that the materials are not expired.

 Verify that required maintenance was performed.

 Verify that the assay was performed according to the instructions for use.

 Rerun the assay with fresh quality control samples.

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 If necessary, contact your local technical supporters or distributors for assistance.

SPECIMEN COLLECTION AND PREPARATION

 Serum collected using standard sampling tubes or tubes containing separating gel, and plasma collected using lithium heparin
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tubes and K2-EDTA tubes could be applied to the assay. Collect blood aseptically following the universal precautions for
venipuncture.
 To ensure consistency in results, specimens must be transferred to a centrifuge tube and centrifuged at 3,000-3,500 RCF
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(Relative Centrifugal Force) for 30 minutes for serum specimens, and 13,000 to 13,500 RCF for 30 minutes for plasma
specimens before testing if they contain fibrin, red blood cells, or other particulate matter.
 Ensure that complete clot formation in specimens has taken place prior to centrifugation. Some serum specimens, especially
those from patients receiving anticoagulant or thrombolytic therapy, may exhibit increased clotting time.
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 If the specimen is centrifuged before a complete clotting, the presence of fibrin may cause erroneous results. Specimens must
be free of fibrin and other particulate matter.
 Do not use hemolyzed or grossly lipemic specimens as well as specimens containing particulate substance or exhibiting
obvious microbial contamination. Inspect all specimens for bubbles, and remove bubbles before analysis for optimal results.
 Avoid repeated freezing and thawing. The sample can be frozen and thawed for only twice. Stored samples should be

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thoroughly mixed prior to use (Vortex mixer). Frozen specimens must be mixed THOROUGHLY after thawing by LOW speed
vortexing. Please ask local representative of SNIBE for more derails if you have any doubt.
 Centrifuged specimens with a lipid layer on the top must be transferred to a sample cup or a secondary tube. Care should be
taken to transfer only the clarified specimen without the lipaemic material.
 All samples (Patient specimens or controls) should be tested within 3 hours when placed on board the MAGLUMI System.
Refer to the SNIBE service for more details of onboard sample storage constraints.
 If testing will be delayed for more than 3 hours, plasma or serum should be removed from red blood cells or clot or separator.
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Specimens removed from the separator, red blood cells or clot may be stored up to 8 hours at 2-8°C, and stored up to 2
months frozen at -20°C or colder.
 Before shipping specimens, it is recommended that specimens be removed from the clot, red blood cells, or separator. When
shipped, specimens should be packaged and labeled in compliance with applicable state, federal and international regulations
covering the transport of clinical specimens and infectious substances. Specimens should be shipped frozen.
 The sample volume required for a single determination of hs-cTnI is 100 µL.
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WARNING AND PRECAUTIONS FOR USERS


 For In Vitro Diagnostic Use.
 Follow the package insert carefully. Reliability of assay results cannot be guaranteed if there are any deviations from the
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instructions in this package insert.

Safety Precautions
 CAUTION: This product requires the handling of human specimens. It is recommended that all human sourced materials be

considered potentially infectious and handled in accordance with the 29 CFR 1910.1030 Occupational exposure to bloodborne
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pathogens. Biosafety Level 2 or other appropriate biosafety practices should be used for materials that contain or are
suspected of containing infectious agents.
 All samples, biological reagents and materials used in the assay should be considered potentially able to transmit infectious

agents. They should therefore be disposed in accordance with the practices of your institution. Discard all materials in a safe
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and acceptable manner and in compliance with prevailing regulatory requirements.

 This product contains Sodium Azide. Dispose of contents and containers must be in accordance with all local, regional and

national regulations.
 Refer to safety data sheets which are available on request.

Handling Precautions
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 Do not use reagent kits beyond the expiration date.

 Do not interchange reagent components from different reagents or lots.

 Prior to loading the reagent kit on the system for the first time, the reagent kit requires mixing to re-suspend magnetic

microbeads that have settled during shipment.

 For magnetic microbeads mixing instructions, refer to the Preparation of the reagent section of this package insert.

 To avoid contamination, wear clean gloves when operating with a reagent kit and samples.
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 Over time, residual liquids may dry on the septum surface. These are typically dried salts which have no effect on assay efficacy.

 For detailed discussion of handling precautions during system operation, refer to the SNIBE service information.

STORAGE AND STABILITY

 Sealed: Stored at 2-8°C until the expiration date.
 Opened at 2-8°C: Minimum stability is 4 weeks.
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 On-board: Minimum stability is 4 weeks.

 To ensure the best kit performance, it is recommended to place opened kits in the refrigerator after the end of the intraday test
work. It is still possible to keep on using the kit beyond the opened or on-board period if the controls are found within the
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expected ranges.
 Keep upright for storage to facilitate later proper resuspension of magnetic microbeads.
 Keep away from sunlight.
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TEST PROCEDURE
Preparation of the Reagent
 Resuspension of the magnetic microbeads takes place automatically when the kit is loaded successfully, ensuring the magnetic
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microbeads are totally resuspended homogenous prior to use.

 To ensure proper test performance, strictly adhere to the operating instructions of MAGLUMI series Fully-auto

chemiluminescence immunoassay analyzer. Each test parameter is identified via a RFID CHIP on the reagent kit. For further
information please refer to the operating instructions of MAGLUMI series Fully-auto chemiluminescence immunoassay
analyzer.

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DILUTION
Sample dilution by analyzer is not available in this reagent kit.
Samples with concentrations above the measuring range can be diluted manually. After manual dilution, multiply the result by the
dilution factor. Please choose applicable diluents or ask SNIBE for advice before manual dilution.
High-Dose Hook
For the hs-cTnI assay, no high dose hook effect was observed when samples containing cTnI up to 20,000 pg/mL.
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LIMITATIONS
 A skillful operation and strict adherence to the instructions are necessary to obtain reliable results. Procedural directions should
be followed exactly and careful operation must be used to obtain valid results. Any modification of the procedure is likely to
alter the results.
 For assays employing antibodies, the possibility exists for interference by heterophile antibodies in the patient sample. Patients
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who have been regularly exposed to animals or received immunotherapy may contain human anti-mouse antibodies (HAMA),
which may result in falsely elevated or decreased values. Moreover, other heterophile antibodies such as human anti-goat
13-15
antibodies may be present in patient samples as well . Additional clinical or diagnostic information may be required to
determine patient status.
 Any condition resulting in myocardial injury can potentially increase cardiac troponin I levels. For myocardial infarction (MI)
diagnostic purposes, the hs-cTnI assay results should be used in conjunction with other information such as ECG, clinical
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observations, and symptoms, etc.

 A single cTnI result may not be sufficient to evaluate MI. Serial blood draws are recommended for evaluation of acute coronary
16,17
syndrome (ACS) patients .
 Although haemolysis has an insignificant effect on the assay, haemolysed samples may indicated mistreatment of a specimen
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before assay and results should be interpreted with caution.

 Lipaemia has an insignificant effect on the assay except in the case of gross lipaemia where spatial interference may occur.

RESULTS
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Calculation of Results
The analyzer automatically calculates the cTnI concentration in each sample by means of a calibration curve which is generated by a
2-point calibration master curve procedure. The results are expressed in pg/mL. For further information please refer to the operating
instructions of MAGLUMI series Fully-auto chemiluminescence immunoassay analyzer.
Interpretation of Results
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The expected range for the hs-cTnI assay was obtained by testing 256 apparently healthy individuals in China, and gave the
following expected value:
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<10 pg/mL (99 percentile).
Results may differ between laboratories due to variations in population and test method. If necessary, each laboratory should
establish its own reference range.
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PERFORMANCE CHARACTERISTICS
Precision
Precision for the hs-cTnI assay was determined as described in the CLSI EP5-A2. 3 human serum pools and 2 controls containing
different concentration of analyte were assayed in duplicate at two independent runs per day for 20 testing days. The result is
summarized in the following table:
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Mean(pg/mL) Within-Run Between-Run Total

Sample
(N=80) SD(pg/mL) %CV SD(pg/mL) %CV SD(pg/mL) %CV
Serum Pool 1 12.009 0.872 7.26 0.086 0.72 0.876 7.29
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Serum Pool 2 480.341 23.977 4.99 10.055 2.09 26.000 5.41

Serum Pool 3 1493.011 47.329 3.17 19.420 1.30 55.961 3.75
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Control 1 8.263 0.483 5.85 0.424 5.13 0.643 7.78

Control 2 23.926 1.262 5.28 0.214 0.89 1.280 5.35

Limit of Blank (LoB)

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The LoB for the hs-cTnI assay is 1.0 pg/mL.

Limit of Detection (LoD)

The LoD for the hs-cTnI assay is 1.5 pg/mL.

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Limit of Quantization (LoQ)

It is defined as the concentration of hs-cTnI that can be measured with an inter assay CV of 10%. The LoQ for the hs-cTnI assay is
3.0 pg/mL.

Measuring Range
1.0-2000 pg/mL (defined by the limit of blank and the maximum of the master curve). Values below the limit of blank are reported
as<1.0 pg/mL. Values above the measuring range are reported as >2000 pg/mL.
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Linearity
The assay is linear between 1.5 pg/mL and 2000 pg/mL based on a study performed with guidance from CLSI EP6-A. Nine
equally distributed levels of samples were prepared by spiking a serum sample containing cTnI 2050 pg/mL with a serum sample
free of cTnI (0.0 pg/mL).The mean sample recovery ranged between 90% to 110%.
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Method Comparison
A total of 258 samples in the range of 6.849 to 1982.60 pg/mL were tested by the hs-cTnI assay(y) and a commercially available
2
immunoassay(x). The data from the resulting linear regressions are summarized as: y=1.0055x-0.7982, r =0.9970.

Analytical Specificity
The specificity data of the assay was obtained by adding these cross-reactant at the indicated concentrations to serum samples at
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the indicated concentrations. The table below lists the substances tested and the concentration at which no significant interference
was observed:
Cross-Reactant Concentration
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Digoxin 200 ng/mL

Paracetamol 250 ng/mL
Nifidipine 400 ng/mL
600 μg/mL
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Aspirin
Propranolol 10 ng/mL
Erythromycin 60 μg/mL
Furadantin 4 μg/mL
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cTnC 1000 ng/mL

cTnT 1000 ng/mL
sTnI 1000 ng/mL

Endogenous Interference
Substances up to the following concentrations did not interfere with the assay:
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 Bilirubin 20 mg/dL
 Triglyceride 500 mg/dL
 Hemoglobin 1000 mg/dL
 ANA +++ (High positive sample)
 RF 1500 IU/mL
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 HAMA 40 ng/mL
 Human Serum Albumin 70 mg/mL

REFERENCES
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1. Perry SV. The regulation of contractile activity in muscle. BiochemSocTrans 1979; 7(4):593-617.
2. Leszyk J, Dumaswala R, Potter JD, Collins JH. Amino acid sequenceof bovine cardiac troponin I. Biochemistry 1988;
27(8):2821-2827.
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3. Solaro RJ. Modulation of cardiac myofilament activity by proteinphosphorylation. In: Page E, Fozzard H, Solaro RJ, editors.
Handbook of physiology. New York7 Oxford University Press; 2001.p. 264–300.
4. Solaro RJ, Moir AJ, Perry SV (1976). "Phosphorylation of troponin I and the inotropic effect of adrenaline in the perfused
rabbit heart". Nature. 262: 615–616.
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5. Zhang P, Kirk, JA, Ji W, dos Remedios CG, Kass DA, Van Eyk JE, Murphy AM (2012). "Multiple Reaction Monitoring to
Identify Site-Specific Troponin I Phosphorylated Residues in the Failing Human Heart". Circulation. 126: 1828–1837
6. Adams JE III, Bodor GS, Davila-Roman VG, et al. Cardiac troponin I: amarker with high specificity for cardiac injury.
Circulation. 1993; 88:101–106.

105 hs-cTnI-en-EU, V7.1, 2018-02 5/6

This document could not be used for the purpose of legal registration.
 Please only refer to the current product lot insert enclosed with the kits package for execution and reporting

7. Cummins B, Auckland ML, Cummins P. Cardiac-specific troponin-Iradioimmuno assay in the diagnosis of acute myocardial
infarction. AmHeart J. 1987; 113:1333–1344.
8. Wu AH, Apple FS, Gibler WB, et al. National Academy of Clinical Biochemistry Standards of Laboratory Practice:
recommendations for theuse of cardiac markers in coronary artery diseases. Clin Chem. 1999; 45:1104–1121.
9. Adams JE III, Sicard GA, Allen BT, et al. Diagnosis of perioperative myocardial infarction with measurement of cardiac
troponin I. N EnglJ Med. 1994;330:670–674.
10. Antman EM, Tanasijevic MJ, Thompson B, et al. Cardiac-specifictroponin I levels to predict the risk of mortality in patients
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with acutecoronary syndromes. N Engl J Med. 1996; 335:1342–1349.
11. Luscher MS, Thygesen K, Ravkilde J, et al. Applicability of cardiactroponin T and I for early risk stratification in unstable
coronary arterydisease: TRIM Study Group: Thrombin Inhibition in Myocardial ischemia. Circulation. 1997; 96:2578–2585.
12. Tanasijevic MJ, Cannon CP, Antman EM. The role of cardiac troponin-I (cTnI) in risk stratification of patients with unstable
coronary arterydisease. ClinCardiol. 1999; 22:13–16.
13. chroff RW, Foon KA, Beatty SM, et al. Human anti-murine immunoglobulin responses in patients receiving monoclonal
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antibody therapy. Cancer Res 1985; 45(2):879-885.

14. Kricka,L. Interference in immunoassays-still a threat. ClinChem 2000; 46:1037-1038.
15. Primus FJ, Kelley EA, Hansen HJ, et al. “Sandwich”-type immunoassay of carcinoembryonic antigen in patients receiving
murine monoclonal antibodies for diagnosis and therapy. ClinChem 1988; 34(2):261-264.
16. Morrow DA, Cannon CP, Jesse RL, et al. National Academy of ClinicalBiochemistry Laboratory Medicine Practice Guidelines:
clinicalcharacteristics and utilization of biochemical markers in acutecoronary syndromes. ClinChem 2007; 53(4):552-574.
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17. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J 2012;
33(20):2551-2567.
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Shenzhen New Industries Biomedical Engineering Co., Ltd.

No.16, Jin hui Road, Ping shan New District, Shenzhen, 518122, P.R. China
Tel: 0086-755-21536601 Fax:0086-755-28292740
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Lotus Global Co., Ltd.

1 Four Seasons Terrace, West Drayton, Middlesex London, UB7 9GG, United Kingdom
Tel: 0044-20-75868010 Fax: 0044-20-79006187
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SYMBOLS EXPLANATIONS

Consult instructions for use Manufacturer

Temperature limit
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Use-by date
( Store at 2-8 °C)

Contains sufficient for Keep away from sunlight

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Authorized representative in the

This way up
European Community

In vitro diagnostic medical device Kit components

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Catalogue number Batch code

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