Cardiovascular disease, intimately linked to dyslipidemia, is one of the leading global causes of mortality. Dyslipidaemia often presents as an elevated concentration of low-density lipoprotein (LDL) and a decreased concentration of high-density lipoprotein (HDL). Therefore, accurately measuring the levels of LDL and HDL particles is crucial for assessing the risk of developing cardiovascular diseases. However, conventional approaches can commonly quantify HDL/LDL particles by detecting cholesterol or protein molecules within them, which may fail to reflect the number of intact particles. In addition, these approaches are sometimes tedious and time-consuming, highlighting the need for a novel method for precise and effective identification of intact HDL and LDL particles. We have devised a technique that allows accurately and sensitively determining the levels of intact HDL and LDL in a sample without the need for isolation. This method relies on antibody-based immobilization and a self-priming hairpin-triggered Cas12a/crRNA signaling strategy. Based on the elegant design, this technique can be employed to directly and precisely measure the concentration of “actual” HDL and LDL particles, rather than the cholesterol content inside HDL and LDL. The approach has detection limits of 12.3 mg dL⁻¹ and 5.4 mg dL⁻¹ for HDL and LDL, respectively, and is also suitable for analyzing lipoproteins in clinical samples. Hence, this platform exhibits immense potential for clinical applications and health management.

中文翻译：

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基于自引发发夹触发的基于 Cas12a/crRNA 的信号转导策略的可靠、精确的脂蛋白检测


心血管疾病与血脂异常密切相关，是全球主要的死亡原因之一。血脂异常通常表现为低密度脂蛋白 （LDL） 浓度升高和高密度脂蛋白 （HDL） 浓度降低。因此，准确测量 LDL 和 HDL 颗粒的水平对于评估患心血管疾病的风险至关重要。然而，传统方法通常可以通过检测其中的胆固醇或蛋白质分子来量化 HDL/LDL 颗粒，而这些颗粒可能无法反映完整颗粒的数量。此外，这些方法有时既乏味又耗时，这凸显了一种精确有效地鉴定完整 HDL 和 LDL 颗粒的新方法的必要性。我们设计了一种技术，无需分离即可准确、灵敏地测定样品中完整 HDL 和 LDL 的水平。该方法依赖于基于抗体的固定和自引发发夹触发的 Cas12a/crRNA 信号转导策略。基于优雅的设计，该技术可用于直接和精确地测量“实际”HDL 和 LDL 颗粒的浓度，而不是 HDL 和 LDL 中的胆固醇含量。该方法对 HDL 和 LDL 的检出限分别为 12.3 mg ^dL-1 和 5.4 mg ^dL-1，也适用于分析临床样品中的脂蛋白。因此，该平台在临床应用和健康管理方面表现出巨大的潜力。