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Chemical tongues: biomimetic recognition using arrays of synthetic polymers

Polymer Journal volume 54, pages 851–862 (2022)Cite this article

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Abstract

Humans can taste and identify numerous comestibles by combining a small variety of taste receptor cells that exhibit broad-spectrum sensitivity with information processing based on pattern recognition. Recently, we have developed a biosensing strategy called the “chemical tongue”, which mimics the taste system by employing polymeric materials containing various chemical structures labeled with environment-responsive fluorophores in conjunction with statistical techniques such as multivariate analysis and machine learning. In this review, the author outlines the design of polymer-based chemical tongues using polyamino acids, DNAs, and polyion complexes and their applications with various complex biological samples, including cell suspensions, cell secretions, and therapeutic antibodies. The chemical-tongue strategy is capable of recognizing biological samples in a unique manner that does not, in contrast to conventional approaches, rely on specific interactions, thereby potentially opening avenues for unexplored uses of polymers in a wide range of research areas.

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References

  1. Holford TRJ, Davis F, Higson SPJ. Recent trends in antibody based sensors. Biosens Bioelectron. 2012;34:12–24.

    Article  CAS  PubMed  Google Scholar 

  2. Kirsch J, Siltanen C, Zhou Q, Revzin A, Simonian A. Biosensor technology: recent advances in threat agent detection and medicine. Chem Soc Rev. 2013;42:8733–68.

    Article  CAS  PubMed  Google Scholar 

  3. Califf RM. Biomarker definitions and their applications. Exp Biol Med. 2018;243:213–21.

    Article  CAS  Google Scholar 

  4. Prasad B, Achour B, Artursson P, Hop CECA, Lai Y, Smith PC, et al. Toward a consensus on applying quantitative liquid chromatography-tandem mass spectrometry proteomics in translational pharmacology research: a white paper. Clin Pharmacol Ther. 2019;106:525–43.

    Article  PubMed  Google Scholar 

  5. Yarmolinsky DA, Zuker CS, Ryba NJP. Common sense about taste: from mammals to insects. Cell. 2009;139:234–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Roper SD, Chaudhari N. Taste buds: cells, signals and synapses. Nat Rev Neurosci. 2017;18:485–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rakow NA, Suslick KS. A colorimetric sensor array for odour visualization. Nature. 2000;406:710–3.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang C, Suslick KS. A colorimetric sensor array for organics in water. J Am Chem Soc. 2005;127:11548–9.

    Article  CAS  PubMed  Google Scholar 

  9. Rakow NA, Sen A, Janzen MC, Ponder JB, Suslick KS. Molecular recognition and discrimination of amines with a colorimetric array. Angew Chem, Int Ed. 2005;44:4528–32.

    Article  CAS  Google Scholar 

  10. Lim SH, Musto CJ, Park E, Zhong W, Suslick KS. A colorimetric sensor array for detection and identification of sugars. Org Lett. 2008;10:4405–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li Z, Askim JR, Suslick KS. The optoelectronic nose: colorimetric and fluorometric sensor arrays. Chem Rev. 2019;119:231–92.

    Article  CAS  PubMed  Google Scholar 

  12. You C-C, Miranda OR, Gider B, Ghosh PS, Kim I-B, Erdogan B, et al. Detection and identification of proteins using nanoparticle-fluorescent polymer “chemical nose” sensors. Nat Nanotechnol. 2007;2:318–23.

    Article  CAS  PubMed  Google Scholar 

  13. Miranda OR, You C-C, Phillips R, Kim I-B, Ghosh PS, Bunz UHF, et al. Array-based sensing of proteins using conjugated polymers. J Am Chem Soc. 2007;129:9856–7.

    Article  CAS  PubMed  Google Scholar 

  14. Miranda OR, Creran B, Rotello VM. Array-based sensing with nanoparticles: “chemical noses” for sensing biomolecules and cell surfaces. Curr Opin Chem Biol. 2010;14:728–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Geng Y, Peveler WJ, Rotello VM. Array‐based “Chemical Nose” sensing in diagnostics and drug discovery. Angew Chem, Int Ed. 2019;58:5190–5200.

    Article  CAS  Google Scholar 

  16. Han J, Bender M, Seehafer K, Bunz UHF. Identification of white wines by using two oppositely charged poly(p-phenyleneethynylene)s individually and in complex. Angew Chem Int Ed. 2016;55:7689–92.

    Article  CAS  Google Scholar 

  17. Han J, Ma C, Wang B, Bender M, Bojanowski M, Hergert M, et al. A hypothesis-free sensor array discriminates whiskies for brand, age, and taste. Chem. 2017;2:817–24.

    Article  CAS  Google Scholar 

  18. Wang B, Han J, Zhang H, Bender M, Biella A, Seehafer K, et al. Detecting counterfeit brandies. Chem—Eur J. 2018;24:17361–6.

    Article  CAS  PubMed  Google Scholar 

  19. Suzuki S, Sawada T, Serizawa T. Identification of water-soluble polymers through discrimination of multiple optical signals from a single peptide sensor. ACS Appl Mater Interfaces. 2021;13:55978–87.

    Article  CAS  PubMed  Google Scholar 

  20. Wu D, Schanze KS. Protein induced aggregation of conjugated polyelectrolytes probed with fluorescence correlation spectroscopy: application to protein identification. ACS Appl Mater Interfaces. 2014;6:7643–51.

    Article  CAS  PubMed  Google Scholar 

  21. Xu S, Lu X, Yao C, Huang F, Jiang H, Hua W, et al. A visual sensor array for pattern recognition analysis of proteins using novel blue-emitting fluorescent gold nanoclusters. Anal Chem. 2014;86:11634–9.

    Article  CAS  PubMed  Google Scholar 

  22. Chang N, Lu Y, Mao J, Yang J, Li M, Zhang S, et al. Ratiometric fluorescence sensor arrays based on quantum dots for detection of proteins. Analyst. 2016;141:2046–52.

    Article  CAS  PubMed  Google Scholar 

  23. Xu S, Gao T, Feng X, Fan X, Liu G, Mao Y, et al. Near infrared fluorescent dual ligand functionalized Au NCs based multidimensional sensor array for pattern recognition of multiple proteins and serum discrimination. Biosens Bioelectron. 2017;97:203–7.

    Article  CAS  PubMed  Google Scholar 

  24. Xu S, Wu Y, Sun X, Wang Z, Luo X. A multicoloured Au NCs based cross-reactive sensor array for discrimination of multiple proteins. J Mater Chem B. 2017;5:4207–13.

    Article  CAS  PubMed  Google Scholar 

  25. Xu S, Su Z, Zhang Z, Nie Y, Wang J, Ge G, et al. Rapid synthesis of nitrogen doped carbon dots and their application as a label free sensor array for simultaneous discrimination of multiple proteins. J Mater Chem B. 2017;5:8748–53.

    Article  CAS  PubMed  Google Scholar 

  26. Pandit S, Banerjee T, Srivastava I, Nie S, Pan D. Machine learning-assisted array-based biomolecular sensing using surface-functionalized carbon dots. ACS Sens. 2019;4:2730–7.

    Article  CAS  PubMed  Google Scholar 

  27. Tomita S, Ishihara S, Kurita R. Biomimicry recognition of proteins and cells using a small array of block copolymers appended with amino acids and fluorophores. ACS Appl Mater Interfaces. 2019;11:6751–8.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang Y, Görner H. Photoprocesses of xanthene dyes bound to lysozyme or serum albumin. Photochem Photobiol. 2009;85:677–85.

    Article  CAS  PubMed  Google Scholar 

  29. Chen H, Ahsan SS, Santiago-Berrios MB, Abruña HD, Webb WW. Mechanisms of quenching of Alexa fluorophores by natural amino acids. J Am Chem Soc. 2010;132:7244–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tomita S, Ishihara S, Kurita R. Environment-sensitive turn-on fluorescent polyamino acid: fingerprinting protein populations with post-translational modifications. ACS Appl Mater Interfaces. 2017;9:22970–6.

    Article  CAS  PubMed  Google Scholar 

  31. Sugai H, Tomita S, Ishihara S, Kurita R. Fingerprint-based protein identification in cell culture medium using environment-sensitive turn-on fluorescent polymer. Sens Mater. 2019;31:1–11.

    CAS  Google Scholar 

  32. Zhuang Y-D, Chiang P-Y, Wang C-W, Tan K-T. Environment‐sensitive fluorescent turn‐on probes targeting hydrophobic ligand‐binding domains for selective protein detection. Angew Chem, Int Ed. 2013;52:8214–8128.

    Article  CAS  Google Scholar 

  33. Majorek KA, Porebski PJ, Dayal A, Zimmerman MD, Jablonska K, Stewart AJ, et al. Structural and immunologic characterization of bovine, horse, and rabbit serum albumins. Mol Immunol. 2012;52:174–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tomita, S, Kusada, H, Kojima, N, Ishihara, S, Miyazaki, K, Tamaki, H et al. Polymer-based chemical nose systems for optical pattern recognition of gut microbiota. ChemRxiv (2020). https://doi.org/10.26434/chemrxiv.12649826.

  35. Sharma TK, Bruno JG, Dhiman A. ABCs of DNA aptamer and related assay development. Biotechnol Adv. 2017;35:275–301.

    Article  CAS  PubMed  Google Scholar 

  36. Lu Y, Liu Y, Zhang S, Wang S, Zhang S, Zhang X. Aptamer-based plasmonic sensor array for discrimination of proteins and cells with the naked eye. Anal Chem. 2013;85:6571–4.

    Article  CAS  PubMed  Google Scholar 

  37. Sun W, Lu Y, Mao J, Chang N, Yang J, Liu Y. Multidimensional sensor for pattern recognition of proteins based on DNA–gold nanoparticles conjugates. Anal Chem. 2015;87:3354–9.

    Article  CAS  PubMed  Google Scholar 

  38. Li C, Yang Y, Wei L, Wang X, Wang Z, Yin Y, et al. An array-based approach to determine different subtype and differentiation of non-small cell lung cancer. Theranostics. 2015;5:62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wei X, Chen Z, Tan L, Lou T, Zhao Y. DNA-catalytically active gold nanoparticle conjugates-based colorimetric multidimensional sensor array for protein discrimination. Anal Chem. 2017;89:556–9.

    Article  CAS  PubMed  Google Scholar 

  40. Wu S, Han Y, Wang L, Li J, Sun Z, Zhang M, et al. Sensor array fabricated with nanoscale metal-organic frameworks for the histopathological examination of colon cancer. Anal Chem. 2019;91:10772–8.

    Article  CAS  PubMed  Google Scholar 

  41. Pei H, Li J, Lv M, Wang J, Gao J, Lu J, et al. A graphene-based sensor array for high-precision and adaptive target identification with ensemble aptamers. J Am Chem Soc. 2012;134:13843–9.

    Article  CAS  PubMed  Google Scholar 

  42. Tomita S, Ishihara S, Kurita R. A multi-fluorescent DNA/graphene oxide conjugate sensor for signature-based protein discrimination. Sensors. 2017;17:2194.

    Article  PubMed Central  CAS  Google Scholar 

  43. Hizir MS, Robertson NM, Balcioglu M, Alp E, Rana M, Yigit MV. Universal sensor array for highly selective system identification using two-dimensional nanoparticles. Chem Sci. 2017;8:5735–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Nandu N, Hizir MS, Yigit MV. Systematic investigation of two-dimensional DNA nanoassemblies for construction of a nonspecific sensor array. Langmuir. 2018;34:14983–92.

    Article  CAS  PubMed  Google Scholar 

  45. Tomita S, Sugai H, Mimura M, Ishihara S, Shiraki K, Kurita R. Optical fingerprints of proteases and their inhibited complexes provided by differential cross-reactivity of fluorophore-labeled single-stranded DNA. ACS Appl Mater Interfaces. 2019;11:47428–36.

    Article  CAS  PubMed  Google Scholar 

  46. Okada M, Sugai H, Tomita S, Kurita R. A multichannel pattern-recognition-based protein sensor with a fluorophore-conjugated single-stranded DNA set. Sensors. 2020;20:5110.

    Article  CAS  PubMed Central  Google Scholar 

  47. De M, Rana S, Akpinar H, Miranda OR, Arvizo RR, Bunz UHF, et al. Sensing of proteins in human serum using conjugates of nanoparticles and green fluorescent protein. Nat Chem. 2009;1:461–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Moyano DF, Rana S, Bunz UHF, Rotello VM. Gold nanoparticle-polymer/biopolymer complexes for protein sensing. Faraday Discuss. 2011;152:33–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tomita S, Yoshimoto K. Polyion complex libraries possessing naturally occurring differentiation for pattern-based protein discrimination. Chem Commun. 2013;49:10430–2.

    Article  CAS  Google Scholar 

  50. Tomita S, Soejima T, Shiraki K, Yoshimoto K. Enzymatic fingerprinting of structurally similar homologous proteins using polyion complex library constructed by tuning PEGylated polyamine functionalities. Analyst. 2014;139:6100–3.

    Article  CAS  PubMed  Google Scholar 

  51. Tomita S, Niwa O, Kurita R. Artificial modification of an enzyme for construction of cross-reactive polyion complexes to fingerprint signatures of proteins and mammalian cells. Anal Chem. 2016;88:9079–86.

    Article  CAS  PubMed  Google Scholar 

  52. Peveler WJ, Landis RF, Yazdani M, Day JW, Modi R, Carmalt CJ, et al. A rapid and robust diagnostic for liver fibrosis using a multichannel polymer sensor array. Adv Mater. 2018;30:1800634.

    Article  CAS  Google Scholar 

  53. Xu S, Li W, Zhao X, Wu T, Cui Y, Fan X, et al. Ultrahighly efficient and stable fluorescent gold nanoclusters coated with screened peptides of unique sequences for effective protein and serum discrimination. Anal Chem. 2019;91:13947–52.

    Article  CAS  PubMed  Google Scholar 

  54. Lin E, Cao T, Nagrath S, King MR. Circulating tumor cells: diagnostic and therapeutic applications. Annu Rev Biomed Eng. 2018;20:329–52.

    Article  CAS  PubMed  Google Scholar 

  55. Solier C, Langen H. Antibody‐based proteomics and biomarker research—current status and limitations. Proteomics. 2014;14:774–83.

    Article  CAS  PubMed  Google Scholar 

  56. Bajaj A, Miranda OR, Kim I-B, Phillips RL, Jerry DJ, Bunz UHF, et al. Detection and differentiation of normal, cancerous, and metastatic cells using nanoparticle-polymer sensor arrays. Proc Natl Acad Sci USA. 2009;106:10912–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. El-Boubbou K, Zhu DC, Vasileiou C, Borhan B, Prosperi D, Li W, et al. Magnetic glyco-nanoparticles: a tool to detect, differentiate, and unlock the glyco-codes of cancer via magnetic resonance imaging. J Am Chem Soc. 2010;132:4490–9.

    Article  CAS  PubMed  Google Scholar 

  58. Jiang Z, Le NDB, Gupta A, Rotello VM. Cell surface-based sensing with metallic nanoparticles. Chem Soc Rev. 2015;44:4264–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Rana S, Elci SG, Mout R, Singla AK, Yazdani M, Bender M, et al. Ratiometric array of conjugated polymers-fluorescent protein provides a robust mammalian cell sensor. J Am Chem Soc. 2016;138:4522–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Tao Y, Li M, Auguste DT. Pattern-based sensing of triple negative breast cancer cells with dual-ligand cofunctionalized gold nanoclusters. Biomaterials. 2017;116:21–33.

    Article  CAS  PubMed  Google Scholar 

  61. Sugai H, Tomita S, Kurita R. Pattern-recognition-based sensor arrays for cell characterization: from materials and data analyses to biomedical applications. Anal Sci. 2020;36:923–34.

    Article  CAS  PubMed  Google Scholar 

  62. Bai H, Liu Z, Zhang T, Du J, Zhou C, He W, et al. Multifunctional supramolecular assemblies with aggregation-induced emission (AIE) for cell line identification, cell contamination evaluation, and cancer cell discrimination. ACS Nano. 2020;14:7552–63.

    Article  CAS  PubMed  Google Scholar 

  63. Rana S, Singla AK, Bajaj A, Elci SG, Miranda OR, Mout R, et al. Array-based sensing of metastatic cells and tissues using nanoparticle-fluorescent protein conjugates. ACS Nano. 2012;6:8233–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Le NDB, Yesilbag Tonga G, Mout R, Kim S-T, Wille ME, Rana S, et al. Cancer cell discrimination using host-guest “doubled” arrays. J Am Chem Soc. 2017;139:8008–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sugai H, Tomita S, Ishihara S, Kurita R. One-component array based on a dansyl-modified polylysine: generation of differential fluorescent signatures for the discrimination of human cells. ACS Sens. 2019;4:827–31.

    Article  CAS  PubMed  Google Scholar 

  66. Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res. 2011;13:215.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Singh VK, Kalsan M, Kumar N, Saini A, Chandra R. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev Biol. 2015;3:2.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Fang Y, Eglen RM. Three-dimensional cell cultures in drug discovery and development. SLAS Discov. 2017;22:456–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Brown KJ, Formolo CA, Seol H, Marathi RL, Duguez S, An E, et al. Advances in the proteomic investigation of the cell secretome. Expert Rev Proteom. 2012;9:337–45.

    Article  CAS  Google Scholar 

  70. Makridakis M, Roubelakis MG, Vlahou A. Stem cells: insights into the secretome. Biochim Biophys Acta. 2013;1834:2380–4.

    Article  CAS  PubMed  Google Scholar 

  71. Brandi J, Manfredi M, Speziali G, Gosetti F, Marengo E, Cecconi D. Proteomic approaches to decipher cancer cell secretome. Semin Cell Dev Biol. 2018;78:93–101.

    Article  CAS  PubMed  Google Scholar 

  72. Stühler K. The secrets of protein secretion: what are the key features of comparative secretomics? Expert Rev Proteom. 2020;17:785–7.

    Article  CAS  Google Scholar 

  73. Tomita S, Sakao M, Kurita R, Niwa O, Yoshimoto K. A polyion complex sensor array for markerless and noninvasive identification of differentiated mesenchymal stem cells from human adipose tissue. Chem Sci. 2015;6:5831–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Tomita S, Nomoto H, Yoshitomi T, Iijima K, Hashizume M, Yoshimoto K. Noninvasive fingerprinting-based tracking of replicative cellular senescence using a colorimetric polyion complex array. Anal Chem. 2018;90:6348–52.

    Article  CAS  PubMed  Google Scholar 

  75. Sugai H, Tomita S, Ishihara S, Yoshioka K, Kurita R. Microfluidic sensing system with a multichannel surface plasmon resonance chip: damage-free characterization of cells by pattern recognition. Anal Chem. 2020;92:14939–46.

    Article  CAS  PubMed  Google Scholar 

  76. Ronaldson-Bouchard K, Vunjak-Novakovic G. Organs-on-a-chip: a fast track for engineered human tissues in drug development. Cell Stem Cell. 2018;22:310–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Grilo AL, Mantalaris A. The increasingly human and profitable monoclonal antibody market. Trends Biotechnol. 2019;37:9–16.

    Article  CAS  PubMed  Google Scholar 

  78. Elgundi Z, Reslan M, Cruz E, Sifniotis V, Kayser V. The state-of-play and future of antibody therapeutics. Adv Drug Deliv Rev. 2017;122:2–19.

    Article  CAS  PubMed  Google Scholar 

  79. Tomita S, Matsuda A, Nishinami S, Kurita R, Shiraki K. One-step identification of antibody degradation pathways using fluorescence signatures generated by cross-reactive DNA-based arrays. Anal Chem. 2017;89:7818–22.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The author would like to express his gratitude to Sayaka Ishihara (National Institute of Advanced Industrial Science and Technology) and Prof. Hiroka Sugai (University of Tsukuba), as well as his other past and present colleagues for their invaluable contributions to this focus review. The author is deeply indebted to Prof. Ryoji Kurita (National Institute of Advanced Industrial Science and Technology), Prof. Osamu Niwa (Saitama Institute of Technology), Prof. Keitaro Yoshimoto (The University of Tokyo), and Prof. Kentaro Shiraki (University of Tsukuba) for their continuous encouragement and constructive discussions. This work was financially supported by JSPS KAKENHI grants JP26810074, JP16K14043, JP17H04884 and JP20H02774, as well as AMED grant JP21wm0425004.

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  1. Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan

    Shunsuke Tomita

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Tomita, S. Chemical tongues: biomimetic recognition using arrays of synthetic polymers. Polym J 54, 851–862 (2022). https://doi.org/10.1038/s41428-022-00636-w

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