大穿透深度折射率传感器对活细胞药物敏感性的研究
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摘要
针对现有表面等离子激元折射率传感器纵向探测深度小、探测范围无法覆盖整个细胞厚度的问题,提出一种大探测深度、高灵敏度的活细胞折射率实时测量方法,并利用该方法开展了药物敏感性的实验研究。基于偏振选择吸收效应,设计并搭建了全内反射条件下的石墨烯折射率传感系统,进行了不同质量分数氯化钠溶液折射率的测量,结果表明系统具有9.5×10~6 mV/RIU的灵敏度和5.5×10~(-7) RIU的分辨率;利用该系统开展了活细胞药物敏感性的实验研究,分别研究了顺铂和紫杉醇作用于Ramos细胞和Jeko-1细胞时生物演化过程中细胞折射率的实时变化规律,验证了折射率变化与其药性机理作用的一致性。
Aiming at the problem that the existing surface plasmon refractive index sensor has a small vertical detection depth and the detection range cannot cover the entire thickness of cells, we propose a real-time measurement method of the living cell refractive index for its advantages: large detection depth and high sensitivity. And this method is used to carry out the experimental research on drug susceptibility. Based on the polarization-selective absorption effect, we design and build a graphene-based refractive index sensing system under the condition of total internal reflection. The refractive index with various mass fraction of sodium chloride solution is measured. The results indicate that the sensitivity and resolution of the system is 9.5×10~6 mV/RIU and 5.5×10~(-7) RIU, respectively. The experimental study on the drug susceptibility of living cells is carried out by the system. The real-time changes of cell refractive index during the biological evolution of cisplatin and paclitaxel in Ramos cells and Jeko-1 cells are studied, and the consistency of refractive index changes with its pharmacological mechanism is verified.
Aiming at the problem that the existing surface plasmon refractive index sensor has a small vertical detection depth and the detection range cannot cover the entire thickness of cells, we propose a real-time measurement method of the living cell refractive index for its advantages: large detection depth and high sensitivity. And this method is used to carry out the experimental research on drug susceptibility. Based on the polarization-selective absorption effect, we design and build a graphene-based refractive index sensing system under the condition of total internal reflection. The refractive index with various mass fraction of sodium chloride solution is measured. The results indicate that the sensitivity and resolution of the system is 9.5×10~6 mV/RIU and 5.5×10~(-7) RIU, respectively. The experimental study on the drug susceptibility of living cells is carried out by the system. The real-time changes of cell refractive index during the biological evolution of cisplatin and paclitaxel in Ramos cells and Jeko-1 cells are studied, and the consistency of refractive index changes with its pharmacological mechanism is verified.
引文
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[21] Raghavan R, Cheriyamundath S, Madassery J. Dimethyl sulfoxide inactivates the anticancer effect of cisplatin against human myelogenous leukemia cell lines in in vitro assays[J]. Indian Journal of Pharmacology, 2015, 47(3): 322-324.
[22] Safinya C R, Chung P J, Song C, et al. The effect of multivalent cations and Tau on paclitaxel-stabilized microtubule assembly, disassembly, and structure[J]. Advances in Colloid and Interface Science, 2016, 232: 9-16.
[23] Yeung T K,Germond C, Chen X M, et al. The mode of action of taxol: apoptosis at low concentration and necrosis at high concentration[J]. Biochemical and Biophysical Research Communications, 1999, 263(2): 398-404.
[24] Altieri D C. Validating survivin as a cancer therapeutic target[J]. Nature Reviews Cancer, 2003, 3(1): 46-54.
[2] Kumawat N, Pal P, Varma M. Diffractive optical analysis for refractive index sensing using transparent phase gratings[J]. Scientific Reports, 2015, 5: 16687.
[3] Sreekanth K V, Alapan Y, ElKabbash M, et al. Extreme sensitivity biosensing platform based on hyperbolic metamaterials[J]. Nature Materials, 2016, 15(6): 621-627.
[4] Xu S C, Zhan J, Man B Y, et al. Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor[J]. Nature Communications, 2017, 8: 14902.
[5] Wang H, Zhou W C, Li K W, et al. Label-free biosensing characteristics of micro/nano-fiber coupler[J]. Acta Optica Sinica, 2017, 37(3): 0306005. 汪海, 周文超, 李凯伟, 等. 微纳光纤耦合器无标生物传感特性[J]. 光学学报, 2017, 37(3): 0306005.
[6] Liu P Y, Chin L K, Ser W, et al. Cell refractive index for cell biology and disease diagnosis past, present and future[J]. Lab on a Chip, 2016, 16(4): 634-644.
[7] Guo T. Review on plasmonic optical fiber grating biosensors[J]. Acta Optica Sinica, 2018, 38(3): 0328006. 郭团. 等离子体共振光纤光栅生物传感器综述[J]. 光学学报, 2018, 38(3): 0328006.
[8] Brule T, Granger G, Bukar N, et al. A field-deployed surface plasmon resonance (SPR) sensor for RDX quantification in environmental waters[J]. Analyst, 2017, 142(12): 2161-2168.
[9] Zeng S W, Baillargeat D, Ho H P, et al. Nanomaterials enhanced surface plasmon resonance for biological and chemical sensing applications[J]. Chemical Society Reviews, 2014, 43(10): 3426-3452.
[10] Wong C L, Olivo M. Surface plasmon resonance imaging sensors: a review[J]. Plasmonics, 2014, 9(4): 809-824.
[11] Slavík R, Homola J. Ultrahigh resolution long range surface plasmon-based sensor[J]. Sensors and Actuators B, 2007, 123(1): 10-12.
[12] Bao Q L, Loh K P. Graphene photonics, plasmonics, and broadband optoelectronic devices[J]. ACS Nano, 2012, 6(5): 3677-3694.
[13] Xing F, Liu Z B, Deng Z C, et al. Sensitive real-time monitoring of refractive indexes using a novel graphene-based optical sensor[J]. Scientific Report, 2012, 2: 908.
[14] Sun L X, Zhang Y Q, Wang Y J, et al. Refractive index mapping of single cells with a graphene-based optical sensor[J]. Sensors and Actuators B, 2017, 242: 41-46.
[15] Xing F, Meng G X, Zhang Q, et al. Ultrasensitive flow sensing of a single cell using graphene-based optical sensors[J]. Nano Letters, 2014, 14(6): 3563-3569.
[16] Xing F, Zhang S, Yang Y, et al. Chemically modified graphene films for high-performance optical NO2 sensors[J]. Analyst, 2016, 141(15): 4725-4732.
[17] Jiang W S, Xin W, Xun S, et al. Reduced graphene oxide-based optical sensor for detecting specific protein[J]. Sensors and Actuators B, 2017, 249: 142-148.
[18] Jiang W S, Xin W, Chen S N, et al. Microshell arrays enhanced sensitivity in detection of specific antibody for reduced graphene oxide optical sensor[J]. Sensors, 2017, 17: 221.
[19] Yang Y, Sun J L, Liu L, et al. Research of detection depth for graphene-based optical sensor[J]. Optics Communications, 2018, 411: 143-147.
[20] Reedijk J, Lohman P H M. Cisplatin: synthesis, antitumour activity and mechanism of action[J]. Pharmaceutisch Weekblad, 1985, 7(5): 173-180.
[21] Raghavan R, Cheriyamundath S, Madassery J. Dimethyl sulfoxide inactivates the anticancer effect of cisplatin against human myelogenous leukemia cell lines in in vitro assays[J]. Indian Journal of Pharmacology, 2015, 47(3): 322-324.
[22] Safinya C R, Chung P J, Song C, et al. The effect of multivalent cations and Tau on paclitaxel-stabilized microtubule assembly, disassembly, and structure[J]. Advances in Colloid and Interface Science, 2016, 232: 9-16.
[23] Yeung T K,Germond C, Chen X M, et al. The mode of action of taxol: apoptosis at low concentration and necrosis at high concentration[J]. Biochemical and Biophysical Research Communications, 1999, 263(2): 398-404.
[24] Altieri D C. Validating survivin as a cancer therapeutic target[J]. Nature Reviews Cancer, 2003, 3(1): 46-54.