Zhang Ya, Liu Xiaofang, Xu Ying, Wang Qun, Hou Jingzhou, Hou Changjun, Huo Danqun
Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of Chongqing University, Chongqing 400044, PR China.
Chongqing Key Laboratory of Bio-perception & Intelligent Information Processing, School of Microelectronics and Communication Engineering, Chongqing University, Chongqing 400044, PR China.
Anal Chem. 2024 Jul 19. doi: 10.1021/acs.analchem.4c01385.
Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki67 are four crucial biomarkers used in the clinical diagnosis of breast cancer. Accurate detection of these biomarkers is essential for an effective diagnosis and treatment. MOF-based micronano motors (MOFtors) are promising for various applications, including environmental remediation, targeted nanosurgery, and biomarker detection. This paper presents a clinically feasible diagnostic electrochemical micronano motor biosensor, built on a miniature swimmer, for the multiplex detection and grading of breast cancer biomarkers. We designed a biosensor, named MOFtor-MSEM, incorporating aptamers and antibodies functionalized on SiO@Co-Fe-MOF, which acts as a miniature swimmer in solution. The SiO@Co-Fe-MOF serves as the body, while complementary double-chain-linked antibodies function as paddles. In a homogeneous solution, when a positive voltage is applied to the working electrode, the electrostatic interaction between the neutral SiO@Co-Fe-MOF and the negatively charged complementary double-linked antibody causes the antibody to move toward the electrode and then regress due to water resistance. This back-and-forth motion propels the miniature swimmer, enabling it to move the target analyte through the solution. The sensor features an automatic "sample-amplifying signal-output" process, achieving simultaneous signal amplification and output of four electrochemical signals on a single nanomaterial, a significant challenge in electrochemical sensing. The biosensor boasts a short detection time of 40 min, compared to approximately 1 week for current clinical tissue testing. Additionally, the bioplatform selectively detects HER2, ER, Ki67, and PR in the range of 0-1500 pg/mL, with detection limits of 0.01420, 0.03201, 0.01430, and 0.01229 pg/mL, respectively.
雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER2）和Ki67是乳腺癌临床诊断中使用的四种关键生物标志物。准确检测这些生物标志物对于有效诊断和治疗至关重要。基于金属有机框架的微米纳米马达（MOFtors）在各种应用中具有广阔前景，包括环境修复、靶向纳米手术和生物标志物检测。本文介绍了一种基于微型游动器构建的临床可行的诊断性电化学微米纳米马达生物传感器，用于乳腺癌生物标志物的多重检测和分级。我们设计了一种名为MOFtor-MSEM的生物传感器，它将适配体和抗体功能化在SiO@Co-Fe-MOF上，SiO@Co-Fe-MOF在溶液中充当微型游动器。SiO@Co-Fe-MOF作为主体，而互补双链连接的抗体充当桨。在均匀溶液中，当向工作电极施加正电压时，中性的SiO@Co-Fe-MOF与带负电荷的互补双链抗体之间的静电相互作用会使抗体向电极移动，然后由于水阻力而退回。这种来回运动推动微型游动器，使其能够在溶液中移动目标分析物。该传感器具有自动的“样品-放大信号-输出”过程，可以在单个纳米材料上同时实现四个电化学信号的放大和输出，这在电化学传感中是一个重大挑战。与目前临床组织检测约1周的时间相比，该生物传感器的检测时间仅为40分钟。此外，该生物平台能够在0-1500 pg/mL的范围内选择性地检测HER2、ER、Ki67和PR，检测限分别为0.01420、0.03201、0.01430和0.01229 pg/mL。
