Abstract
Background
Light‐initiated chemiluminescent assay (LiCA) is a new homogeneous immunoassay. The aim of this study was to evaluate the analytical and clinical performance of the assays for the detection of thyroid hormones based on the fully automated LiCA 800 analyzer.
Methods
Analytical validations of the LiCA thyroid assays (TSH, FT3, FT4, T3, and T4) included precision, linearity, analytical sensitivity, interference, and method comparison applying the protocols of the Clinical and Laboratory Standards Institute (CLSI). The diagnostic performance was assessed by the receiver operating characteristic (ROC) curve analysis with different assay schemes for the diagnosis of hyperthyroidism and hypothyroidism.
Results
Within‐run and within‐lab precisions (%CV) of the five assays ranged from 1.06 to 6.40% at all concentrations evaluated. A satisfactory linearity was verified over the entire measuring range for TSH, T3, and T4 (R > 0.99, change in recovery <10%, p = 0.000 all). Paired‐comparison measurements presented a comparable assay for each of the five assays (R > 0.96, median bias <5%, p < 0.0001 all) between LiCA and Cobas across three institutes. The diagnostic accuracy of the LiCA assays for hyperthyroidism or hypothyroidism was quantified by the areas under curves (AUC) as 0.925 or 0.832 with the five‐assay panel (TSH, FT3, FT4, T3, and T4) and as 0.921 or 0.811 with the three‐assay panel (TSH, FT3, and FT4), respectively. No significant difference was found between the AUC of LiCA and that of DxI, Cobas, or Centaur (p > 0.3 all).
Conclusion
LiCA 800 provides a precise and high‐throughput immunoassay platform for detection of thyroid hormones. It is acceptable for clinical use.
Keywords: LiCA 800 analyzer, light‐initiated chemiluminescent assay, performance evaluation, thyroid assay, thyroid disease
In this study, we have validated the analytical and diagnostic performance of the LiCA thyroid assays. Paired‐comparison measurements demonstrated a reasonable concordance for each of the assays (R > 0.96, median bias <5%, p < 0.0001 all) between LiCA and Cobas across three institutes. To further characterize the clinical performance of the LiCA assays for the diagnosis of hyperthyroidism and hypothyroidism, we compared the AUCs with the five‐assay panel (TSH, FT3, FT4, T3, and T4) and with the three‐assay panel (TSH, FT3, and FT4) between LiCA and other three commonly used methods (DxI, Cobas, and Centaur). No significant difference was found (p > 0.3 all), and this confirmed the diagnostic accuracy and applicable in clinical practice of the LiCA thyroid assays.
1. INTRODUCTION
Laboratory tests of thyroid hormones are essential for clinical diagnosis and patient management of thyroid diseases. 1 , 2 The key assays include thyroid‐stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), and thyroxine (T4). With overt advantages on high sensitivity and specificity, full automation, high‐throughput, and non‐radioactive contamination, chemiluminescent immunoassay (CLIA) is gradually taking the leading position for the thyroid tests in clinical laboratory. 3 Due to lack of harmonization on the international level of reference materials, detection of thyroid assays could be variant from different platforms based on different methodologies. Thereby, a performance validation is necessary before a new assay could be admitted in clinical application.
In this study, we introduced a new homogeneous light‐initiated chemiluminescent assay (LiCA®) that was derived from the luminescent oxygen‐channeling immuno‐technology described by Ullman et al. 4 , 5 The key analytical characteristics of the five thyroid assays (TSH, FT3, FT4, T3, and T4) were assessed following the guidelines of the Clinical and Laboratory Standards Institute (CLSI). In addition, the diagnostic performance was analyzed by the receiver operating characteristic (ROC) curve with different assay schemes for the diagnosis of hyperthyroidism and hypothyroidism.
2. MATERIALS AND METHODS
2.1. Study samples
The evaluation study of the five thyroid assays (TSH, FT3, FT4, T3, and T4) was conducted at the clinical laboratory of Peking University international Hospital. Additional method comparison between LiCA and Cobas was validated at other two institutes in China. All samples were collected from residual and de‐identified patient sera within 2 h after clinical routine thyroid assays. We selected specimens based on serum quality, volume, and analyte concentrations. Subjects with visible icterus, lipemia, or hemolysis were excluded. Unless otherwise noted, specimens were stored at −20°C for no longer than 30 days with one freeze‐thaw cycle in this study.
2.2. LiCA® thyroid assays
The LiCA® thyroid assay (Chemclin Diagnostics, Beijing, China) uses two nanobeads (sensitizer and emission) to bridge a fully homogeneous immunoassay. When the antigen‐antibody complex is formed after incubation, the distance between two beads is less than 200 nm. Singlet oxygen generated from the sensitizer by light at 680 nm diffuses to the emission bead across the complex, thus triggering a chemiluminescent reaction. In contrast, no emission occurs if there is no antigen‐antibody reaction, as a longer distance (>200 nm) blocks energy transmission. Therefore, no‐wash is necessary to separate the immune complex from free components in the cuvette, and thus, this test delivers a fast and stable measurement. 6 , 7 , 8 The LiCA 800 analyzer used in this study is a fully automated, random‐access, and high‐throughput (600 tests per hour) immunoassay platform. Time to the first report for each of the LiCA thyroid assays (TSH, FT3, FT4, T3, and T4) is 32 min. The assay specifications have been summarized in Table 1.
TABLE 1.
Specifications of the LiCA thyroid assays
| Assay | Sample volume | Measuring range | Reference range | Traceability | Antibodies used | Immunoassay principle |
|---|---|---|---|---|---|---|
| TSH | 25 μl | 0.010–100 mIU/L | 0.270–4.200 mIU/L |
WHO IRP 80/558 |
Mouse monoclonal | Sandwich |
| FT3 | 10 µl | 1.54–76 pmol/L | 3.10–6.80 pmol/L | Manufacturer reference | Sheep monoclonal | Competitive |
| FT4 | 10 µl | 3.86–75 pmol/L | 12.00–22.00 pmol/L | Manufacturer reference | Mouse monoclonal | Competitive |
| T3 | 10 µl | 0.62–9.22 nmol/L | 1.30–3.10 nmol/L | USP grade material | Sheep monoclonal | Competitive |
| T4 | 10 µl | 12.87–410 nmol/L | 66.00–181.00 nmol/L | USP grade material | Mouse monoclonal | Competitive |
Abbreviations: IRP, International Reference Preparation; USP, United States Pharmacopeia; WHO, World Health Organization.
2.3. Precision study
A precision study was performed for each of the LiCA thyroid assays in accordance with the CLSI EP15‐A3 protocol. 9 Repeatability (within‐run) and within‐laboratory (intermediate) imprecision (coefficient of variation, CV) were determined using three levels of pooled human sera. 25 measurements were collected for each sample in 5 runs over 5 days.
2.4. Linearity study
The linearity study (for TSH, T3, and T4) followed the CLSI EP6‐A protocol. 10 Two human serum samples for each of the assays were collected according to the analytical upper and lower limits of the manufacturer's claims. Eleven dilution pools were prepared for linearity experiments. Each dilution was measured 4 times, and linearity was evaluated by regression analysis.
2.5. Analytical sensitivity study
We followed the CLSI EP17‐A2 protocol 11 to examine the limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) for the LiCA thyroid assays. The LoB experiment was performed with the zero‐point manufacturer's calibrator. LoD and LoQ were determined using serial low levels of pooled sera. Each sample was aliquoted into 20 tubes. Triplicate measurements were performed during 20 runs over 5 days (n = 60).
2.6. Interference study
To evaluate for possible interference of hemolysis, lipemia, and icterus in the LiCA thyroid assays, three levels of patient serum samples were spiked according to manufacturer's claims with interferents that included hemoglobin (2.5 g/L), triglycerides (5.65 mmol/L), and bilirubin (171 μmol/L), respectively. Each sample was measured in duplicate, and percent recovery was calculated for the evaluation of interference.
2.7. Method comparison study
A three‐site comparison study was carried out for the LiCA and Cobas thyroid assays following the guideline of CLSI EP9‐A2. 12 Serum specimens were collected from randomly selected patients with analyte concentrations across the analytical measuring range. All samples were assayed on the same day with the Cobas e602 (Roche Diagnostics) and LiCA 800 analyzers. Measuring agreement was evaluated by linear regression and bias plot.
2.8. Clinical performance study
A total of 377 serum specimens were enrolled from patients with suspected thyroid dysfunction at presentation, of which 55 subjects were finally confirmed with hyperthyroidism and 62 with hypothyroidism. The diagnosis was made in the presence of hyperthyroidism or hypothyroidism‐related signs and symptoms and laboratory testing support by independent clinicians. Results of the Centaur‐thyroid‐assays (Siemens Healthcare Diagnostics) were used for adjudication of the final diagnosis. Patients who had been receiving treatment for thyroid diseases were excluded. Each sample was separated into four tubes and stored at −80°C. Measurements were recorded by Cobas e602, DxI 800 (Beckman Coulter), Centaur XP, and LiCA 800 on the same day. Diagnostic performance was analyzed by receiver operating characteristic (ROC) curve.
2.9. Statistical analysis
Statistical analysis was performed with the software program SPSS (IBM Corp.), MedCalc (MedCalc Software Ltd.) and Excel (Microsoft Corp.). Concordance of paired measurements was assessed by Passing–Bablok linear regression and Bland–Altman bias plot. ROC curves were computed with five‐assay panel (TSH, FT3, FT4, T3, and T4) and three‐assay panel (TSH, FT3, and FT4) for two groups of patients (hyperthyroidism and hypothyroidism), respectively. Areas under curves (AUCs) were calculated to quantify the diagnostic accuracy of the assays as described by DeLong et al. 13 A statistical significance was considered as p < 0.05.
3. RESULTS
3.1. Precision
As shown in Table 2, the within‐run CV% of each assay ranged from 1.06% to 5.63% and the within‐lab CV% from 1.55% to 6.40%, across low, middle, and high levels of pooled human sera. Our findings revealed that LiCA provided a good precision in thyroid assays.
TABLE 2.
Precision analysis with the EP15‐A3 protocol
| Assay | Mean (n = 25) | Within‐run precision | Within‐lab precision | ||
|---|---|---|---|---|---|
| SD | %CV | SD | %CV | ||
| TSH (mIU/L) | 0.065 | 0.002 | 3.65 | 0.003 | 4.24 |
| 1.663 | 0.034 | 2.06 | 0.041 | 2.46 | |
| 22.941 | 0.407 | 1.78 | 0.580 | 2.53 | |
| FT3 (pmol/L) | 1.65 | 0.079 | 4.79 | 0.088 | 5.34 |
| 5.25 | 0.264 | 5.03 | 0.279 | 5.32 | |
| 14.04 | 0.791 | 5.63 | 0.898 | 6.40 | |
| FT4 (pmol/L) | 6.55 | 0.135 | 2.07 | 0.172 | 2.63 |
| 15.79 | 0.499 | 3.16 | 0.515 | 3.26 | |
| 34.93 | 1.347 | 3.86 | 1.477 | 4.23 | |
| T3 (nmol/L) | 0.65 | 0.007 | 1.06 | 0.011 | 1.67 |
| 1.99 | 0.037 | 1.87 | 0.051 | 2.57 | |
| 6.49 | 0.201 | 3.08 | 0.193 | 2.97 | |
| T4 (nmol/L) | 41.37 | 0.543 | 1.31 | 0.641 | 1.55 |
| 127.83 | 2.129 | 1.67 | 2.501 | 1.96 | |
| 273.49 | 9.742 | 3.56 | 10.431 | 3.81 | |
Abbreviations: CV, coefficient of variation; SD: standard deviation.
3.2. Linearity
The regression equation and Pearson's correlation coefficient between the expected and measured values were (Y = 1.024X − 1.663, R = 0.999) for TSH, (Y = 0.966X + 0.040, R = 0.997) for T3, and (Y = 0.973X − 1.450, R = 0.998) for T4, respectively. p = 0.000 all. The percent recovery obtained for each dilution was 96.4%–106.2% for TSH, 94.1%–107.4% for T3, and 95.6%–107.8% for T4, respectively. The hypothesis of a linear fit was accepted for each of the assays.
3.3. Analytical sensitivity
The results of LoB, LoD, and LoQ (20% CV) for the LiCA thyroid assays were displayed in Table 3. Our observations agreed with the manufacturer's claims.
TABLE 3.
Determination of analytical sensitivity with the EP17‐A2 protocol
| Assay | Observed values | Manufacturer claimed Detection limit | ||
|---|---|---|---|---|
| LoB | LoD | LoQ | ||
| TSH (mIU/L) | 0.001 | 0.002 | 0.002 | ≤0.010 |
| FT3 (pmol/L) | 0.20 | 0.34 | 0.72 | ≤1.54 |
| FT4 (pmol/L) | 1.00 | 1.28 | 1.28 | ≤3.86 |
| T3 (nmol/L) | 0.11 | 0.17 | 0.22 | ≤0.62 |
| T4 (nmol/L) | 2.04 | 6.10 | 9.40 | ≤12.87 |
Abbreviations: LoB, limit of blank; LoD, limit of detection; LoQ, limit of quantitation (at 20% coefficient of variation).
3.4. Interferences
No analytical interference was observed for the LiCA thyroid assays in the presence of hemoglobin (2.5 g/L), triglycerides (5.65 mmol/L), and bilirubin (171 μmol/L) as claimed by the manufacturer (Table 4). The percent recovery for each of the assays was determined to be between 92.5% and 108.0% across low, middle, and high levels of serum samples.
TABLE 4.
Interference study for endogenous substances
| Assay | Baseline concentration | Percent recovery after spiking the interferents | ||
|---|---|---|---|---|
| Hemoglobin (2.5 g/L) | Triglycerides (5.65 mmol/L) | Bilirubin (171 µmol/L) | ||
| TSH | 0.237 | 96.7% | 92.5% | 97.0% |
| (mIU/L) | 2.871 | 93.9% | 96.3% | 94.0% |
| 23.146 | 92.7% | 101.3% | 94.0% | |
| FT3 | 1.88 | 106.3% | 94.6% | 107.2% |
| (pmol/L) | 4.96 | 104.1% | 94.4% | 106.1% |
| 12.95 | 97.4% | 95.0% | 103.2% | |
| FT4 | 6.09 | 102.8% | 95.9% | 103.2% |
| (pmol/L) | 18.17 | 107.7% | 98.4% | 104.4% |
| 40.42 | 103.6% | 93.4% | 105.9% | |
| T3 | 0.89 | 105.7% | 98.5% | 108.0% |
| (nmol/L) | 2.22 | 103.3% | 98.8% | 107.6% |
| 5.27 | 101.9% | 105.1% | 101.9% | |
| T4 | 38.24 | 98.5% | 96.4% | 107.0% |
| (nmol/L) | 116.25 | 98.8% | 94.8% | 106.3% |
| 220.23 | 104.6% | 99.9% | 107.6% | |
3.5. Method comparison
A method comparison study between LiCA and Cobas was performed using a larger pool of serum specimens across the analytical measuring range in our lab. Figure 1(A–E) showed the paired plots of Passing‐Bablok regression and Bland–Altman bias for each of the thyroid assays (TSH, FT3, FT4, T3, and T4). The Spearman's correlation coefficient R (95% CI: confidence interval) was 0.992 (0.990–0.994), 0.981 (0.976–0.985), 0.974 (0.967–0.979), 0.969 (0.961–0.976), and 0.972 (0.964–0.978), respectively (p < 0.0001 all). The median percent difference (95% CI) was −3.55% (−7.01% ~ −1.10%), 0.40% (−2.07% ~ 2.17%), 2.90% (0.33% ~ 5.69%), −3.00% (−4.56% ~ 0.01%), and −3.95% (−6.20% ~ −2.20%), respectively. A paired‐comparison experiment was repeated in other two institutes in China, and results reproduced the comparable measurements between the LiCA and Cobas thyroid assays. The detailed analyses of the multicenter comparison were summarized in Table 5 as a quick overview.
FIGURE 1.
Passing‐Bablok linear regression and Bland–Altman plot analyses for measurement comparison between LiCA and Cobas thyroid assays in serum specimens using the EP9‐A2 protocol. Abbreviations: N, sample number; R, Spearman's rank correlation coefficient; SD, standard deviation
TABLE 5.
Overview of multicenter comparison between LiCA and Cobas thyroid assays in serum specimens following the EP9‐A3 protocol
| Assay | Institute | N | Sample range | Slope (95% CI) | Intercept (95% CI) | R (95% CI) | Median Bias (95% CI) | |
|---|---|---|---|---|---|---|---|---|
| % | Value | |||||||
| TSH (mIU/L) | A | 288 | 0.010 ~ 99.020 | 1.031 (1.009 ~ 1.052) | −0.063 (−0.097 ~ −0.039) | 0.992* (0.990 ~ 0.994) | −3.55% (−7.01 ~ −1.10%) | −0.029 (−0.060 ~ −0.004) |
| B | 131 | 0.011 ~ 98.585 | 0.981 (0.958 ~ 0.995) | 0.002 (−0.010 ~ 0.005) | 0.995* (0.992 ~ 0.996) | −1.60% (−5.22 ~ 2.48%) | −0.015 (−0.076 ~ 0.004) | |
| C | 122 | 0.010 ~ 99.533 | 0.998 (0.980 ~ 1.022) | −0.008 (−0.040 ~ 0.022) | 0.994* (0.992 ~ 0.996) | −1.20% (−3.80 ~ 1.89%) | −0.008 (−0.068 ~ 0.029) | |
| FT3 (pmol/L) | A | 289 | 1.54 ~ 71.70 | 0.989 (0.962 ~ 1.013) | 0.100 (−0.068 ~ 0.244) | 0.981* (0.976 ~ 0.985) | 0.40% (−2.07 ~ 2.17%) | 0.02 (−0.14 ~ 0.14) |
| B | 140 | 1.54 ~ 73.74 | 1.045 (1.005 ~ 1.094) | −0.062 (−0.299 ~ 0.168) | 0.977* (0.968 ~ 0.984) | 3.15% (0.28 ~ 7.65%) | 0.22 (0.02 ~ 0.48) | |
| C | 126 | 2.05 ~ 69.82 | 1.012 (0.967 ~ 1.057) | −0.245 (−0.525 ~ 0.028) | 0.966* (0.952 ~ 0.976) | −2.60% (−7.85 ~ 0.64%) | −0.16 (−0.41 ~ 0.06) | |
| FT4 (pmol/L) | A | 297 | 2.12 ~ 74.37 | 0.931 (0.896 ~ 0.966) | 1.480 (0.913 ~ 2.010) | 0.974* (0.967 ~ 0.979) | 2.90% (0.33 ~ 5.69%) | 0.47 (0.05 ~ 0.77) |
| B | 132 | 3.87 ~ 71.67 | 0.987 (0.951 ~ 1.024) | 0.425 (−0.141 ~ 1.028) | 0.983* (0.976 ~ 0.988) | 1.40% (0.50 ~ 2.70%) | 0.24 (0.06 ~ 0.50) | |
| C | 128 | 3.86 ~ 74.39 | 0.946 (0.908 ~ 0.989) | 0.345 (−0.405 ~ 1.138) | 0.983* (0.975 ~ 0.988) | −3.60% (−5.10~−0.79%) | −0.58 (−0.96 ~ −0.18) | |
| T3 (nmol/L) | A | 255 | 0.26 ~ ~ 9.20 | 1.069 (1.025~1.115) | −0.193 (−0.305 ~ −0.093) | 0.969* (0.961 ~ ~ 0.976) | −3.00% (−4.56 ~ 0.01%) | −0.06 (−0.10~0.01) |
| B | 128 | 0.62 ~ 8.97 | 0.915 (0.876 ~ 0.949) | 0.278 (0.198 ~ −0.351) | 0.965* (0.950 ~ 0.975) | 3.95% (0.14 ~ 6.57%) | 0.09 (0.01 ~ 0.14) | |
| C | 124 | 0.62~9.15 | 0.992 (0.959 ~ 1.035) | 0.092 (0.017 ~ −0.160) | 0.974* (0.963 ~ 0.982) | 4.35% (0.62 ~ 6.81%) | 0.09 (0.02 ~ 0.12) | |
| T4 (nmol/L) | A | 254 | 7.87 ~ 360.06 | 0.946 (0.916 ~ 0.977) | 1.744 (−2.032 ~ 3.967) | 0.972* (0.964 ~ 0.978) | −3.95% (−6.20 ~ −2.20%) | −5.09 (−6.96 ~ −2.97) |
| B | 128 | 12.87 ~ 370.66 | 0.956 (0.909 ~ 1.001) | 6.753 (2.458 ~ −10.688) | 0.968* (0.955 ~ 0.977) | 2.75% (0.59 ~ 6.41%) | 2.50 (0.52 ~ 5.24) | |
| C | 113 | 12.87 ~ 372.77 | 0.966 (0.898 ~ 1.042) | −0.924 (−9.289 ~ 5.250) | 0.963* (0.947 ~ 0.975) | −4.70% (−8.82 ~ −1.82%) | −4.72 (−8.39 ~ −1.72) | |
Abbreviations: CI, confidence interval; N, sample number; R, Spearman's rank correlation coefficient.
*p < 0.0001.
3.6. Clinical performance
ROC curves were plotted in Figure 2 to describe the diagnostic accuracy of the assays. Using the five‐assay panel (TSH, FT3, FT4, T3, and T4) for the diagnosis of hyperthyroidism (Figure 2A) and hypothyroidism (Figure 2C), the AUCs (95% CI) were 0.925 (0.880–0.957) and 0.832 (0.777–0.878) for LiCA, comparable with DxI at 0.915 (0.869–0.949, p = 0.4678) and 0.818 (0.761–0.866, p = 0.6670), with Cobas at 0.926 (0.882–0.958, p = 0.8525) and 0.840 (0.786–0.885, p = 0.7955), with Centaur at 0.932 (0.888–0.962, p = 0.4283) and 0.823 (0.767–0.870, p = 0.7395), respectively. ROC curve analyses using the tree‐assay panel (TSH, FT3, and FT4) revealed a comparable diagnostic accuracy for hyperthyroidism (Figure 2B) and hypothyroidism (Figure 2D) between LiCA and DxI, Cobas, or Centaur, while the AUC was slightly lower than that generated by the five‐assay panel.
FIGURE 2.
Receiver operating characteristic (ROC) curve analyses of thyroid assays for the diagnosis of hyperthyroidism and hypothyroidism. Abbreviations: AUC, area under curve
4. DISCUSSION
The essential principle of LiCA technology is singlet oxygen channeling through two kinds of nanoscale latex beads—sensitizer and emission. 7 , 8 The sensitizer contains the photosensitive dyes and is coated with streptavidin. The emission bead is coated with an assay‐specific antibody and contains the chemiluminescent dyes. Singlet oxygen transfer occurs only if the distance between two beads is within 200 nm (when the immune complex is formed) and triggers a cascade of chemical reactions. The reagent nanobeads provide three bases for the LiCA assays: (1) a fully homogeneous environment; (2) a larger specific surface area; and (3) a multi‐amplification signaling chemiluminescence. This enables LiCA offering a sensitive, no‐wash, rapid and stable immunoassay. 6 , 7 , 8 Various assays based on this technology have been developed recently. 14 , 15 , 16 In this study, we have validated the analytical and diagnostic performance of the LiCA thyroid assays.
Our data demonstrated a good precision for each of the five assays. Within‐run and within‐lab imprecisions across three levels of pooled sera were less than 6.5%. Satisfactory linearity was verified over the entire measuring range for TSH, T3, and T4 as previously claimed. Pearson's correlation coefficients were between 0.997–0.999 with all p values of 0.000, and the maximum change in recovery was within 8%. FT3 and FT4 are not applicable for linearity dilution, as there is an equilibrium for T3 and T4 in the blood with free and protein‐bound forms. A change in the concentration of binding proteins alters this equilibrium.
The analyzed LoD in this study agrees with the manufacturer's claim for each of the assays. However, there are no data issued for the LoQs in the product instructions for use. Our study may be one useful supplementary. Notably, the LoQ of LiCA TSH was determined to be 0.0019 mIU/L, and this was in accordance with the criteria of a fourth‐generation TSH method. 17 A more extensive evaluation for LiCA TSH would be described in another work.
Paired‐comparison measurements demonstrated a comparable assay for each of the assays (R > 0.96, median bias <5%, p < 0.0001 all) between LiCA and Cobas across three institutes. To further characterize the clinical performance of the LiCA assays for the diagnosis of hyperthyroidism and hypothyroidism, we compared the AUCs with the five‐assay panel (TSH, FT3, FT4, T3, and T4) and with the three‐assay panel (TSH, FT3, and FT4) between LiCA and other three commonly used methods (DxI, Cobas, and Centaur). No significant difference was found (p > 0.3 all), and this confirmed the diagnostic accuracy and applicable in clinical practice of the LiCA thyroid assays.
In conclusion, LiCA 800 provides a precise and high‐throughput immunoassay platform for the detection of thyroid hormones. It is acceptable for clinical use.
CONFLICT OF INTEREST
All authors state no conflict of interests.
PATIENT CONSENT
All samples used in this study were collected from residual and de‐identified patient sera that were clinically tested for the thyroid assays. A waiver of the informed consent has been approved by the Biomedical Ethics Committee of Peking University International Hospital (No. 2021‐KY‐0002–01).
PERMISSION TO REPRODUCE MATERIAL FROM OTHER SOURCES
Not applicable.
CLINICAL TRIAL REGISTRATION
Not applicable.
Li J, Huang Y, Xiang G, et al. Analytical and clinical evaluation of the light‐initiated chemiluminescent assays for measurement of human thyroid hormones. J Clin Lab Anal. 2022;36:e24266. doi: 10.1002/jcla.24266
Jing Li and Youyuan Huang as co‐first authors contributed equally to this work.
DATA AVAILABILITY STATEMENT
The datasets generated during the current study are available from the corresponding author on reasonable request.
REFERENCES
- 1. Baloch Z, Carayon P, Conte‐Devolx B, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13(1):3‐126. [DOI] [PubMed] [Google Scholar]
- 2. Feldt‐Rasmussen U, Klose M. Clinical strategies in the testing of thyroid function. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW , Dhatariya K, et al., Endotext. MDText.com, Inc., Copyright © 2000‐2021, MDText.com, Inc; 2020. [Google Scholar]
- 3. Kricka LJ. Chemiluminescence. Cold Spring Harb Protoc. 2018;2018:4. [DOI] [PubMed] [Google Scholar]
- 4. Ullman EF, Kirakossian H, Switchenko AC, et al. Luminescent oxygen channeling assay (LOCI): sensitive, broadly applicable homogeneous immunoassay method. Clin Chem. 1996;42(9):1518‐1526. [PubMed] [Google Scholar]
- 5. Ullman EF, Kirakossian H, Singh S, et al. Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence. Proc Natl Acad Sci USA. 1994;91(12):5426‐5430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Bielefeld‐Sevigny M. AlphaLISA immunoassay platform‐ the "no‐wash" high‐throughput alternative to ELISA. Assay Drug Dev Technol. 2009;7(1):90‐92. [DOI] [PubMed] [Google Scholar]
- 7. Hou C, Zhao L, Geng F, Wang D, Guo LH. Donor/acceptor nanoparticle pair‐based singlet oxygen channeling homogenous chemiluminescence immunoassay for quantitative determination of bisphenol A. Anal Bioanal Chem. 2016;408(30):8795‐8804. [DOI] [PubMed] [Google Scholar]
- 8. Tian Y, Lv J, Wang J, Qin Y, Liu J, Zhao W. A light initiated chemiluminescent immunoassay for procalcitonin. Acta Biochim Biophys Sin (Shanghai). 2014;46(9):817‐819. [DOI] [PubMed] [Google Scholar]
- 9. CLSI . User Verification of Precision and Estimation of Bias; Approved Guideline‐Third Edition. CLSI Document EP15‐A3. Clinical and Laboratory Standards Institute; 2014. [Google Scholar]
- 10. CLSI . Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline. CLSI document EP6‐A. Clinical and Laboratory Standards Institute; 2003. [Google Scholar]
- 11. CLSI . Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline‐Second Edition. CLSI Document EP17‐A2. Clinical and Laboratory Standards Institute; 2012. [Google Scholar]
- 12. CLSI . Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline‐Second Edition. CLSI document EP9‐A2. Clinical and Laboratory Standards Institute; 2002. [Google Scholar]
- 13. DeLong ER, DeLong DM, Clarke‐Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837‐845. [PubMed] [Google Scholar]
- 14. Yang S, Yang R, Zhang S, et al. Clinical diagnostic performance of light‐initiated chemiluminescent assay compared with the Architect chemiluminescence immunoassay for detection of HCV antibody. J Clin Lab Anal. 2019;33(7):e22928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Li J, Li S, Huang L, et al. A light‐initiated chemiluminescent assay for rapid quantitation of allergen‐specific IgG4 in clinical samples. Clin Chim Acta. 2019;489:83‐88. [DOI] [PubMed] [Google Scholar]
- 16. Zhang Y, Liang Y, Feng L, Cui L. Diagnostic performance of 14‐3‐3eta and anti‐carbamylated protein antibodies in Rheumatoid Arthritis in Han population of Northern China. Clin Chim Acta. 2020;502:102‐110. [DOI] [PubMed] [Google Scholar]
- 17. Spencer CA, Schwarzbein D, Guttler RB, LoPresti JS, Nicoloff JT. Thyrotropin (TSH)‐releasing hormone stimulation test responses employing third and fourth generation TSH assays. J Clin Endocrinol Metab. 1993;76(2):494‐498. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during the current study are available from the corresponding author on reasonable request.