Department of Ophthalmology, Keimyung University School of Medicine, 1035 Dalgubeol-daero, Dalseo-gu, Daegu, 42601, Republic of Korea.
Department of Biomedical Engineering, University of Rochester, Rochester, New York, United States of America.
Sci Rep. 2020 Sep 15;10(1):15126. doi: 10.1038/s41598-020-71977-w.
We aimed to validate a tear MMP-9 in-situ immunoassay (InflammaDry) and to identify factors that could affect results or interpretation. Three factors were examined: sample concentration, volume, and time. Recombinant human (rh) MMP-9 (10 or 20 μl; 0, 12.5, 25, 50, 100, 200, 500, and 1,000 ng/ml) was applied to the kit and the detection limit and assay reproducibility were examined. At a rhMMP-9 volume of 10 μl (≥ 50 ng/ml), all positive results were identified by densitometry at 10 and 20 min; however, after 20 min, more than half of the nine ophthalmologists interpreted a positive result. At a rhMMP-9 volume of 20 μl (≥ 25 ng/ml), ophthalmologists and densitometry identified almost all test lines at 10 and 20 min. At 10 μl, densitometry showed a linear dose-response pattern. At 20 μl, densitometry showed a linear dose-response pattern at concentrations up to 500 ng/ml; however, full saturation was achieved at concentrations ≥ 500 ng/ml. When the same amount of rhMMP-9 was applied, the density result increased significantly upon doubling of the solvent volume (i.e., by adding the same volume of PBS to a sample). InflammaDry showed a high inter- and intra-assay coefficient of variation at 10 min (28.4% and 24.7%, respectively). The results of the MMP-9 in-situ immunoassay varied significantly depending on sample volume. Therefore, when interpreting the results, careful attention must be paid to tear volume.
我们旨在验证一种泪液中基质金属蛋白酶-9(MMP-9)的原位免疫检测(InflammaDry),并确定可能影响检测结果或解释的因素。考察了三个因素:样本浓度、体积和时间。向试剂盒中加入重组人(rh)MMP-9(10 或 20 μl;0、12.5、25、50、100、200、500 和 1000 ng/ml),检测检测限和检测重复性。在 rhMMP-9 体积为 10 μl(≥50 ng/ml)时,所有阳性结果在 10 和 20 分钟时通过密度法均能识别;然而,在 20 分钟后,超过一半的 9 位眼科医生解读为阳性结果。在 rhMMP-9 体积为 20 μl(≥25 ng/ml)时,眼科医生和密度法几乎能在 10 和 20 分钟时识别所有的测试线。在 10 μl 时,密度法显示出线性剂量反应模式。在 20 μl 时,密度法在浓度高达 500 ng/ml 时显示出线性剂量反应模式;然而,在浓度≥500 ng/ml 时达到完全饱和。当相同量的 rhMMP-9 被应用时,溶剂体积加倍后(即,向样本中加入相同体积的 PBS),密度结果显著增加。InflammaDry 在 10 分钟时显示出较高的批内和批间变异系数(分别为 28.4%和 24.7%)。MMP-9 原位免疫检测的结果因样本体积而异。因此,在解释结果时,必须密切注意泪液量。