Toxicology and bedside medical condition monitoring is often desired to be both ultrasensitive and noninvasive. However, current biomarker analyses for these purposes are mostly offline and fail to detect low marker quantities. Here, we report a system called dLABer (detection of living animal’s exhaled breath biomarker) that integrates living rats, breath sampling, microfluidics, and biosensors for the automated tracking of breath-borne biomarkers. Our data show that dLABer could selectively detect (online) and report differences (of up to 10³-fold) in the levels of inflammation agent interleukin-6 (IL-6) exhaled by rats injected with different ambient particulate matter (PM). The dLABer system was further shown to have an up to 10⁴ higher signal-to-noise ratio than that of the enzyme-linked immunosorbent assay (ELISA) when analyzing the same breath samples. In addition, both blood-borne IL-6 levels analyzed via ELISA in rats injected with different PM extracts and PM toxicity determined by a dithiothreitol (DTT) assay agreed well with those determined by the dLABer system. Video recordings further verified that rats exposed to PM with higher toxicity (according to a DTT assay and as revealed by dLABer) appeared to be less physically active. All the data presented here suggest that the dLABer system is capable of real-time, noninvasive monitoring of breath-borne biomarkers with ultrasensitivity. The dLABer system is expected to revolutionize pollutant health effect studies and bedside disease diagnosis as well as physiological condition monitoring at the single-protein level.

中文翻译：

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体内自动进行的呼吸调节蛋白蛋白生物标志物的纳米感测

通常希望毒理学和床边医疗状况监测既超敏感又无创。但是，当前用于这些目的的生物标志物分析大部分都处于离线状态，并且无法检测到少量的标志物。在这里，我们报告了一个名为dLABer（活体动物呼出气生物标志物的检测）的系统，该系统集成了活体大鼠，呼吸采样，微流控技术和生物传感器，可自动跟踪呼吸传播的生物标志物。我们的数据表明，dLABer可以选择性地（在线）检测并报告被不同环境颗粒物（PM）注射的大鼠呼出的炎症因子白细胞介素6（IL-6）的水平差异（最多10 ³倍）。dLABer系统进一步显示出最多10 ⁴分析相同的呼吸样本时，信噪比比酶联免疫吸附测定（ELISA）高。此外，在注射了不同PM提取物的大鼠中，通过ELISA分析的两种血源性IL-6水平以及通过二硫苏糖醇（DTT）测定法测定的PM毒性均与dLABer系统测定的结果相吻合。录像进一步证实，暴露于具有较高毒性（根据DTT分析并由dLABer揭示）的PM的大鼠似乎身体活动较少。此处提供的所有数据表明，dLABer系统能够以超灵敏性实时，无创地监测呼吸传播的生物标志物。dLABer系统有望彻底改变污染物健康影响研究和床边疾病诊断以及单一蛋白水平的生理状况监测。