Aggregation-induced emission luminogens in in vitro diagnostics: Advancing biomarker detection in body fluids

Abstract

Rapid, sensitive, and accurate detection of ingredients in body fluids is crucial for monitoring health status and diagnosing diseases. Fluorescent biosensors have emerged as a user-friendly tool for biomarker detection, because of their high sensitivity, rapid response, and adaptability. Among the various signal probes used in fluorescent biosensors, aggregation-induced emission (AIE) luminogens (AIEgens) stand out as a highly promising candidate owing to their unique property of enhanced emission in the aggregated or solid state. This review outlines the sensing mechanisms and design strategies of AIE probes for constructing AIE-based fluorescent biosensors. It provides a comprehensive overview of recent advancements in AIE probes for detecting various ingredients in body fluids, including blood, urine, saliva, throat swabs, and sweat. The efficacy of AIEgen-based fluorescent biosensors in these applications is highlighted, focusing on the design of probes, response mechanisms, and luminescence principles. Finally, the current challenges of AIEgen-based biosensors and future research perspectives are discussed, aiming to inspire the development of AIE probes and improve the sensitivity and accessibility of AIEgen-based fluorescent biosensors.

Keywords

aggregation-induced emission luminogens / biosensors / body fluids / fluorescence / in vitro diagnostics

References

[1] A. J. Steckl, P. Ray, ACS Sens. 2018, 3, 2025.

[2] J. Yang, L. Huang, K. Qian, Exploration 2022, 2, 20210222.

[3] W. Cui, A. Xiao, C. Luo, X. Wu, J. Zheng, P. Chen, J. Liang, H. Wu, B.-O. Guan, Y. Huang, Chem. Eng. J. 2024, 490, 151376.

[4] C. Liu, T. Zhao, J. Zhou, X. Hu, D. Pan, J. Li, W. Li, Z. Dai, Chin. Chem. Lett. 2025, 110967.

[5] L. Zhang, Z. Yang, K. Sefah, K. M. Bradley, S. Hoshika, M. J. Kim, H. J. Kim, G. Zhu, E. Jimenez, S. Cansiz, I. T. Teng, C. Champanhac, C. McLendon, C. Liu, W. Zhang, D. L. Gerloff, Z. Huang, W. Tan, S. A. Benner, J. Am. Chem. Soc. 2015, 137, 6734.

[6] X. Ying, W. Fu, L. Zhu, T. Sun, M. Qi, L. Zhou, Y. Wang, J. Wang, B. Su, J. Zhang, Anal. Chem. 2024, 96, 10630.

[7] A. Rescalli, E. M. Varoni, F. Cellesi, P. Cerveri, Biosensors 2022, 12, 687.

[8] L. Zhang, K. Cao, Y. Su, S. Hu, X. Liang, Q. Luo, H. Luo, Biosens. Bioelectron. 2023, 222, 114935.

[9] Q. Gao, S. Li, Interdiscip. Med. 2024, 2, e20230031.

[10] Z. Cao, R. Yan, J. Chen, M. She, S. Jia, W. Sun, P. Liu, S. Zhang, J.-L. Li, J. Am. Chem. Soc. 2024, 146, 33651.

[11] J. Yang, Z. Xu, L. Yu, B. Wang, R. Hu, J. Tang, J. Lv, H. Xiao, X. Tan, G. Wang, J.-X. Li, Y. Liu, P.-L. Shao, B. Zhang, Angew. Chem. Int. Ed. 2024, 63, e202318800.

[12] Y. Lei, Y. Wang, S. K. Hill, Z. Cheng, Q. Song, S. Perrier, Adv. Mater. 2024, 36, 2401346.

[13] J. Wang, C. Jiang, J. Jin, L. Huang, W. Yu, B. Su, J. Hu, Angew. Chem. Int. Ed. 2021, 60, 13042.

[14] Y. Zhu, L. Ao, S. Chu, Y. Liao, J. Wang, J. Hu, L. Huang, Adv. Funct. Mater. 2024, 34, 2316147.

[15] Z. Wang, L. Yan, Z. Song, J. Zhang, Y. Yang, X. Liu, J. Colloid Interface Sci. 2025, 688, 172.

[16] M. Gu, X. Zheng, C. Li, Z. Zheng, G. Song, L. Xu, L. Chen, D. Zhang, Nano Today 2025, 62, 102675.

[17] L. Zhang, X. Kang, F. Yang, W. Jia, L. Yang, C. Jiang, Anal. Chem. 2025, 97, 3515.

[18] Z. Zhang, S. Shikha, J. Liu, J. Zhang, Q. Mei, Y. Zhang, Anal. Chem. 2019, 91, 548.

[19] Y. Ma, M. Song, L. Li, X. Lao, M.-C. Wong, J. Hao, Exploration 2022, 2, 20210216.

[20] L. Pan, X. Li, Q. Zhang, S. Xu, L. Yang, F. Yang, C. Jiang, Chem. Eng. J. 2022, 450, 138283.

[21] R. Chen, C. Ren, M. Liu, X. Ge, M. Qu, X. Zhou, M. Liang, Y. Liu, F. Li, ACS Nano 2021, 15, 8996.

[22] Y. Gui, Y. Wang, D. Wang, Y. Qin, G. Song, D. Yan, B. Z. Tang, D. Wang, Angew. Chem. Int. Ed. 2024, 63, e202318609.

[23] R. Abellan, R. Ventura, S. Pichini, M. Sarda, A. Remacha, J. Pascual, I. Palmi, A. Bacosi, R. Pacifici, P. J. Zuccaro, J. Segura, J. Immunol. Methods 2004, 295, 89.

[24] W. Wu, M. Shen, X. Liu, L. Shen, X. Ke, W. Li, Biosens. Bioelectron. 2020, 150, 111912.

[25] L. Du, H. Shen, C. Xu, X. Zhu, B. Wang, Q. Zhou, C. Liu, H. H. Y. Sung, R. T. K. Kwok, J. W. Y. Lam, Q. Zhou, T.-M. Liu, B. Z. Tang, Adv. Mater. 2025, 37, 2414419.

[26] L. Zhu, G. Song, W. Zhang, Y. Wu, Y. Chen, J. Song, D. Wang, G. Li, B. Z. Tang, Y. Li, Nat. Commun. 2025, 16, 2578.

[27] B. Wang, S. Liu, X. Liu, R. Hu, A. Qin, B. Z. Tang, Adv. Healthcare Mater. 2021, 10, 2101067.

[28] G. Zhang, T. Liu, H. Cai, Y. Hu, Z. Zhang, M. Huang, J. Peng, W. Lai, ACS Nano 2024, 18, 2346.

[29] B. Wu Kenry, F. Hu, Interdiscip. Med. 2024, 2, e20230038.

[30] X. Wang, R. Wan, Y. Tang, S. Sun, H. Chen, L. Li, J. Chen, J. Wei, Z. Chi, H. Li, Coord. Chem. Rev. 2025, 531, 216520.

[31] L. Dou, Q. Li, Z. Wang, J. Shen, W. Yu, ACS Sens. 2022, 7, 3243.

[32] X. Cai, B. Liu, Angew. Chem., Int. Ed. 2020, 59, 9868.

[33] K. Ren, B. Zhang, J. Guo, H. Cao, J. Cheng, J. Guo, D. Li, Biosens. Bioelectron. 2025, 271, 117067.

[34] Y. Duo, G. Luo, W. Zhang, R. Wang, G. G. Xiao, Z. Li, X. Li, M. Chen, J. Yoon, B. Z. Tang, Chem. Soc. Rev. 2023, 52, 1024.

[35] Y. Liao, Z. Peng, X. Liu, Y. Hu, J. Zhang, Interdiscip. Med. 2023, 1, e20230024.

[36] X. Huang, Q. Guo, R. Zhang, Z. Zhao, Y. Leng, J. W. Y. Lam, Y. Xiong, B. Z. Tang, Compr. Rev. Food Sci. Food Saf. 2020, 19, 2297.

[37] X. Chen, Q. Yang, X. Lv, Y. Xiong, B. Zhong Tang, X. Huang, Coord. Chem. Rev. 2024, 516, 215970.

[38] Y. Yang, G.-B. Hu, W.-B. Liang, L.-Y. Yao, W. Huang, Y.-J. Zhang, J.-L. Zhang, J.-M. Wang, R. Yuan, D.-R. Xiao, Nanoscale 2020, 12, 5932.

[39] X. Chen, Q. Liu, J. Zhang, L. Tan, J. Li, M. L. Ke, B. Z. Tang, Y. Li, ACS Nano 2025, 19, 6221.

[40] X. Chen, K. Wang, Q. Liu, L. Tan, H. Dong, Y. Li, B. Z. Tang, Sensor. Actuat. B Chem. 2025, 427, 137201.

[41] J. Li, H. Jia, X. Ren, Y. Li, L. Liu, R. Feng, H. Ma, Q. Wei, Small 2022, 18, 2106567.

[42] J. Xue, L. Yang, Y. Du, Y. Ren, X. Ren, H. Ma, D. Wu, H. Ju, Y. Li, Q. Wei, Sensor. Actuat. B Chem. 2020, 321, 128454.

[43] C. Chen, L. Chen, Y. Yang, R. He, Y. Deng, J. Hu, Sensor. Actuat. B Chem. 2024, 401, 134961.

[44] J. Zhang, Y. Li, F. Chai, Q. Li, D. Wang, L. Liu, B. Z. Tang, X. Jiang, Sci. Adv. 2022, 8, eabo1874.

[45] M. Wang, Y. Yang, Q. Tang, Y. Zeng, Z. Li, Z. Fu, L. Li, J. Fluoresc. 2025, 35, 3301.

[46] X. Ou, J. Dai, Y. Huang, X. Xiong, Z. Zheng, X. Lou, F. Xia, Giant 2022, 11, 100110.

[47] Q. Liu, X. Chen, J. Li, L. Tan, K. Wang, J. Zhang, H. Dong, Y. Li, B. Z. Tang, Biosens. Bioelectron. 2025, 271, 117068.

[48] H. Li, Y. Hao, Z. Zhang, L. Liu, H. Wang, H. Ma, Q. Wei, Chem. Eng. J. 2024, 500, 156813.

[49] Y. Zhang, R. Miao, H. Sha, W. Ma, Y. Huang, H. Chen, J. Colloid Interface Sci. 2024, 669, 419.

[50] X. Chen, Z.-W. Li, H. Duan, Y.-W. Sun, Y. Su, S. Peng, Y. Guo, Y. Xiong, B. Z. Tang, X. Huang, Adv. Mater. 2024, 36, 2313381.

[51] X. Wei, X. Chen, Z. Liu, G. Xu, G. Chen, X. Lin, W. Zhan, X. Huang, Y. Xiong, Anal. Chim. Acta 2023, 1247, 340869.

[52] F. Gao, M. Liu, W. Wang, J. Lou, Y. Chang, N. Xia, Spectrochim. Acta, Part A 2025, 325, 125088.

[53] X. Chen, X. Wei, S. Cheng, Z. Liu, Y. Su, Y. Xiong, X. Huang, Microchim. Acta 2023, 190, 56.

[54] Y. Hu, S. Cheng, L. Chen, L. Xie, H. Fu, Z. Sun, R. Hu, Y. Liu, Z. Wang, B. Z. Tang, Sensor. Actuat. B Chem. 2024, 408, 135562.

[55] F. Chai, D. Wang, F. Shi, W. Zheng, X. Zhao, Y. Chen, C. Mao, J. Zhang, X. Jiang, Nano Lett. 2023, 23, 9056.

[56] X. Zhang, R. Kong, Q. Tan, F. Qu, F. Qu, Talanta 2017, 169, 1.

[57] Y. Su, X. Chen, H. Huang, Y. Wu, X.-a. Shen, X. Lin, K. Sun, X.-Y. Fan, X. Huang, Y. Xiong, Aggregate 2024, 5, e459.

[58] Y. Hong, C. Feng, Y. Yu, J. Liu, J. W. Lam, K. Q. Luo, B. Z. Tang, Anal. Chem. 2010, 82, 7035.

[59] N. Dey, B. Maji, S. Bhattacharya, Chem. Asian J. 2018, 13, 664.

[60] R. Zhang, S. H. P. Sung, G. Feng, C. J. Zhang, Kenry , B. Z. Tang, B. Liu, Anal. Chem. 2018, 90, 1154.

[61] X. Li, Z. Zhou, Y. Tang, C. Cheng Zhang, Y. Zheng, J. Gao, Q. Wang, Sensor. Actuat. B Chem. 2018, 276, 95.

[62] S. Muthusamy, L. Zhao, K. Rajalakshmi, D. Zhu, R. Soy, J. Mack, T. Nyokong, S. Wang, K.-B. Lee, W. Zhu, Dyes Pigm. 2021, 193, 109556.

[63] C. Wang, J. Cao, Y. Li, Y. Qiao, J. Gao, L. Wang, X. Zhang, L. Wang, Microchem. J. 2025, 208, 112555.

[64] G. Dai, P. Zhao, L. Song, Z. He, D. Liu, X. Duan, Q. Yang, W. Zhao, J. Shen, T. Asakawa, M. Zheng, H. Lu, Biosci. Trends 2023, 17, 234.

[65] H. Ashiba, M. Yasuura, T. Fukuda, K. Hatano, M. Fujimaki, Anal. Chim. Acta 2022, 1213, 339926.

[66] L. H. Xiong, X. He, Z. Zhao, R. T. K. Kwok, Y. Xiong, P. F. Gao, F. Yang, Y. Huang, H. H. Sung, I. D. Williams, J. W. Y. Lam, J. Cheng, R. Zhang, B. Z. Tang, ACS Nano 2018, 12, 9549.

[67] Y. Guo, Y. Zhou, H. Duan, D. Xu, M. Wei, Y. Wu, Y. Xiong, X. Chen, S. Wang, D. Liu, X. Huang, H. Xin, Y. Xiong, B. Z. Tang, Nat. Commun. 2024, 15, 8560.

[68] T. Chen, N. Xie, L. Viglianti, Y. Zhou, H. Tan, B. Z. Tang, Y. Tang, Faraday Discuss. 2017, 196, 351.

[69] C. Liu, Y. Hang, T. Jiang, J. Yang, X. Zhang, J. Hua, Talanta 2018, 178, 847.

[70] R. Tejpal, M. Kumar, V. Bhalla, Sensor. Actuat. B Chem. 2018, 258, 841.

[71] P. Yin, Q. Niu, T. Li, T. Wei, J. Chen, X. Qin, J. Mol. Liq. 2020, 316, 113845.

[72] A. Jain, S. De, P. Saraswat, J. Haribabu, J. F. Santibanez, P. Barman, J. Mol. Struct. 2024, 1310, 138383.

[73] P. Singh, P. Sharma, J. Photochem. Photobiol. A 2021, 408, 113096.

[74] F. Bu, B. Zhao, W. Kan, L. Wang, B. Song, J. Wang, Z. Zhang, Q. Deng, G. Yin, Spectrochim. Acta A. Mol. Biomol. Spectrosc. 2019, 223, 117333.

[75] C. Li, Y. Chen, L. Yang, C. Zhang, B. Wang, Y. Wang, Sensor. Actuat. B Chem. 2019, 291, 25.

[76] Q. Wang, Q. Chen, C. Li, Q. Lai, F. Zou, F. Liang, G. Jiang, J. Wang, Microchem. J. 2020, 153, 104503.

[77] A. H. Upadhaya, H. A. Mirgane, S. P. Pandey, V. S. Patil, S. V. Bhosale, P. K. Singh, Langmuir 2024, 40, 19357.

[78] R. Hu, Y. Yan, L. Jiang, C. Huang, X. Shen, Microchim. Acta 2022, 189, 324.

[79] Y. Zhuang, M. Zhang, B. Chen, R. Duan, X. Min, Z. Zhang, F. Zheng, H. Liang, Z. Zhao, X. Lou, F. Xia, Anal. Chem. 2015, 87, 9487.

[80] Y. Hu, J. Liu, X. You, C. Wang, Z. Li, W. Xie, Sensors 2017, 17, 2246.

[81] Z. An, S. Chen, X. Tong, H. He, J. Han, M. Ma, Y. Shi, X. Wang, Langmuir 2019, 35, 2649.

[82] J. Zhan, Y. Cai, P. Cheng, L. Zheng, K. Pu, Chem. Soc. Rev. 2025, 54, 3906.

[83] V. G. Naik, V. Kumar, A. C. Bhasikuttan, K. Kadu, S. R. Ramanan, A. A. Bhosle, M. Banerjee, A. Chatterjee, ACS Appl. Bio Mater. 2021, 4, 1813.

[84] H. Irshad, Khadija , K. Qvortrup, J. Mol. Liq. 2024, 414, 126049.

[85] Z.-H. Sun, X.-X. Zhang, D. Xu, J. Liu, R.-J. Yu, C. Jing, H.-X. Han, W. Ma, Talanta 2021, 225, 121963.

[86] G.-Q. Zhang, Z. Gao, J. Zhang, H. Ou, H. Gao, R. T. K. Kwok, D. Ding, B. Z. Tang, Cell Rep. Phys. Sci. 2022, 3, 100740.

[87] T. Komatsu, M. Tokeshi, S.-K. Fan, Biosens. Bioelectron. 2022, 195, 113631.

[88] H. Fan, R. Li, Y. Chen, Q. Da, C. Xiong, Y. Zhang, Z. Qin, G. L. Liu, L. Huang, Chem. Eng. J. 2024, 501, 157495.

[89] R. Chen, X. Chen, Y. Zhou, T. Lin, Y. Leng, X. Huang, Y. Xiong, ACS Nano 2022, 16, 3351.

[90] J. Li, Y. Liu, T. Wu, Z. Xiao, J. Du, H. Liang, C. Zhou, J. Zhou, Nat. Commun. 2024, 15, 5603.

[91] L. Fan, W. Yan, Q. Chen, F. Tan, Y. Tang, H. Han, R. Yu, N. Xie, S. Gao, W. Chen, Z. Chen, P. Zhang, Anal. Chem. 2024, 96, 401.

[92] X. Cao, Y. Gu, Z. Li, S. Ge, Y. Mao, Y. Gu, D. Lu, Sensor. Actuat. B Chem. 2023, 375, 132894.

[93] L. Gao, X. Lin, X. Chen, Talanta 2020, 212, 120763.

[94] J. Shu, Y. Li, H. Cai, Q. Fu, C. Li, J. Yuan, Y. Zhao, C. Liu, H. Wu, D. Ling, Z. Liu, G. Su, Q. Cao, X. Huang, R. Chen, P. Yang, Aggregate 2024, 5, e551.

[95] X.-a. Shen, X. Chen, H. Zhou, S. Chen, J. Wu, X. Li, X. Huang, Y. Xiong, Chem. Eng. J. 2024, 497, 154825.

[96] Y. Ju, Y. Yang, Q. Tang, M. Wang, Y. Zeng, Z. Zhang, Y. Zhai, H. Wang, L. Li, Anal. Chim. Acta 2023, 1278, 341692.

[97] R. Chen, X. Zhou, Y. Wu, Q. Liu, Q. Liu, J. Huang, F. Li, Sensor. Actuat. B Chem. 2021, 328, 129050.

[98] S. Yeasmin, G. Ammanath, Y. Ali, B. O. Boehm, U. H. Yildiz, A. Palaniappan, B. Liedberg, ACS Appl. Mater. Interfaces 2020, 12, 31270.

[99] L. Hao, R. T. Zhao, N. L. Welch, E. K. W. Tan, Q. Zhong, N. S. Harzallah, C. Ngambenjawong, H. Ko, H. E. Fleming, P. C. Sabeti, S. N. Bhatia, Nat. Nanotechnol. 2023, 18, 798.

[100] R. R. Nair, J. M. An, J. Kim, D. Kim, Coord. Chem. Rev. 2023, 494, 215336.

[101] R. Gupta, K. Paul, J. Mater. Chem. B 2024, 12, 9037.

[102] A. A. Ksenofontov, P. S. Bocharov, K. V. Ksenofontova, E. V. Antina, J. Mol. Liq. 2022, 345, 117031.

[103] D. Moni, M. Sasmal, A. Katarkar, A. Basu, M. Ali, J. Mater. Chem. B 2024, 12, 8791.

[104] Q. Hu, B. Yao, T. C. Owyong, S. Prashanth, C. Wang, X. Zhang, W. W. H. Wong, Y. Tang, Y. Hong, Chem. Asian J. 2021, 16, 1245.

[105] Z. Zhu, X. Chen, H. Liao, L. Li, H. Yang, Q. Wang, W.-H. Zhu, Aggregate 2024, 5, e526.

[106] Y. Yang, J. Dong, H. Li, D. Guo, W. Yang, Q. Pan, ChemistrySelect 2020, 5, 11483.

[107] A. Jain, S. De, D. Mukherjee, J. Haribabu, J. F. Santibanez, P. Barman, Spectrochim. Acta, Part A 2024, 322, 124824.

[108] R. Chen, B. Li, X. Qin, S. Xing, H. Ren, F. Ma, J. Chen, Q. Niu, Talanta 2024, 273, 125953.

[109] L. Wang, T. Wang, G. Wu, D. Tian, Anal. Methods 2024, 16, 427.

[110] X. Yang, T. Li, X. Chen, H. Zhang, C. Liu, C. Tao, H. Nie, Talanta 2025, 286, 127471.

[111] S. Halder, S. Samanta, G. Das, Analyst 2019, 144, 2696.

[112] H. Nie, W. Ji, J. Cui, X. Liang, X. Yang, J. Bai, X. Zhang, Anal. Chim. Acta 2022, 1236, 340578.

[113] Q. Hu, M. Iwanaga, Y. Tang, Adv. Opt. Mater. 2024, 12, 2400868.

[114] W. Huang, N. Jiang, X. Lv, Y. Qu, X. Zhang, L. Wang, Dyes Pigm. 2024, 221, 111820.

[115] T. Gao, X. Huang, S. Huang, J. Dong, K. Yuan, X. Feng, T. Liu, K. Yu, W. Zeng, J. Agric. Food Chem. 2019, 67, 2377.

[116] X. Lou, Y. Zhuang, X. Zuo, Y. Jia, Y. Hong, X. Min, Z. Zhang, X. Xu, N. Liu, F. Xia, B. Z. Tang, Anal. Chem. 2015, 87, 6822.

[117] Y. Zhuang, Q. Xu, F. Huang, P. Gao, Z. Zhao, X. Lou, F. Xia, ACS Sens. 2016, 1, 572.

[118] H. Xie, F. Zeng, S. Wu, Biomacromolecules 2014, 15, 3383.

[119] M. Song, H. Bai, P. Zhang, X. Zhou, B. Ying, Int. J. Oral Sci. 2023, 15, 2.

[120] B. Ning, T. Yu, S. Zhang, Z. Huang, D. Tian, Z. Lin, A. Niu, N. Golden, K. Hensley, B. Threeton, C. J. Lyon, X.-M. Yin, C. J. Roy, N. S. Saba, J. Rappaport, Q. Wei, T. Y. Hu, Sci. Adv. 2021, 7, eabe3703.

[121] M. D. T. Torres, W. R. de Araujo, L. F. de Lima, A. L. Ferreira, C. de la Fuente-Nunez, Matter 2021, 4, 2403.

[122] Y. Li, C. Lin, Y. Peng, J. He, Y. Yang, Sensor. Actuat. B Chem. 2022, 365, 131974.

[123] Y. Zhang, Y. Sun, J. Han, M. Zhang, F. Li, D. Yang, Talanta 2025, 287, 127644.

[124] T. R. Ray, M. Ivanovic, P. M. Curtis, D. Franklin, K. Guventurk, W. J. Jeang, J. Chafetz, H. Gaertner, G. Young, S. Rebollo, J. B. Model, S. P. Lee, J. Ciraldo, J. T. Reeder, A. Hourlier-Fargette, A. J. Bandodkar, J. Choi, A. J. Aranyosi, R. Ghaffari, S. A. McColley, S. Haymond, J. A. Rogers, Sci. Transl. Med. 2021, 13, eabd8109.

[125] Z. Zhang, R. T. K. Kwok, Y. Yu, B. Z. Tang, K. M. Ng, ACS Appl. Mater. Interfaces 2017, 9, 38153.

[126] J. Zou, X. Wang, C. Xiong, J. Wu, F. Zhang, Z. Mao, Sensor. Actuat. B Chem. 2024, 417, 136154.

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