Improving engineered biological systems with electronics and microfluidics

1. Cameron, D. E., Bashor, C. J. & Collins, J. J. A brief history of synthetic biology. Nat. Rev. Microbiol. 12, 381–390 (2014).

   Article  CAS  PubMed  Google Scholar 

2. Brophy, J. A. N. & Voigt, C. A. Principles of genetic circuit design. Nat. Methods 11, 508–520 (2014).

   Article  CAS  PubMed  PubMed Central  Google Scholar 

3. Way, J. C., Collins, J. J., Keasling, J. D. & Silver, P. A. Integrating biological redesign: where synthetic biology came from and where it needs to go. Cell 157, 151–161 (2014).

   Article  CAS  PubMed  Google Scholar 

4. Nielsen, J. & Keasling, J. D. Engineering cellular metabolism. Cell 164, 1185–1197 (2016).

   Article  CAS  PubMed  Google Scholar 

5. Nielsen, A. A. K. et al. Genetic circuit design automation. Science 352, aac7341 (2016).

   Article  PubMed  Google Scholar 

6. Jones, T. S., Oliveira, S. M. D., Myers, C. J., Voigt, C. A. & Densmore, D. Genetic circuit design automation with Cello 2.0. Nat. Protoc. 17, 1097–1113 (2022).

   Article  CAS  PubMed  Google Scholar 

7. Angermueller, C., Pärnamaa, T., Parts, L. & Stegle, O. Deep learning for computational biology. Mol. Syst. Biol. 12, 878 (2016).

   Article  PubMed  PubMed Central  Google Scholar 

8. Shetty, R. P., Endy, D. & Knight, T. F. Jr. Engineering BioBrick vectors from BioBrick parts. J. Biol. Eng. 2, 5 (2008).

   Article  PubMed  PubMed Central  Google Scholar 

9. Purnick, P. E. M. & Weiss, R. The second wave of synthetic biology: from modules to systems. Nat. Rev. Mol. Cell Biol. 10, 410–422 (2009).

   Article  CAS  PubMed  Google Scholar 

10. Kwok, R. Five hard truths for synthetic biology. Nature 463, 288–290 (2010).

    Article  CAS  PubMed  Google Scholar 

11. Lee, S. Y. et al. A comprehensive metabolic map for production of bio-based chemicals. Nat. Catal. 2, 18–33 (2019).

    Article  CAS  Google Scholar 

12. Keasling, J. D. Manufacturing molecules through metabolic engineering. Science 330, 1355–1358 (2010).

    Article  CAS  PubMed  Google Scholar 

13. Khalil, A. S. & Collins, J. J. Synthetic biology: applications come of age. Nat. Rev. Genet. 11, 367–379 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

14. Pei, L., Garfinkel, M. & Schmidt, M. Bottlenecks and opportunities for synthetic biology biosafety standards. Nat. Commun. 13, 2175 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

15. Whitesides, G. M. The origins and the future of microfluidics. Nature 442, 368–373 (2006).

    Article  CAS  PubMed  Google Scholar 

16. Lan, F., Demaree, B., Ahmed, N. & Abate, A. R. Single-cell genome sequencing at ultra-high-throughput with microfluidic droplet barcoding. Nat. Biotechnol. 35, 640–646 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

17. Abate, A. R., Hung, T., Mary, P., Agresti, J. J. & Weitz, D. A. High-throughput injection with microfluidics using picoinjectors. Proc. Natl Acad. Sci. USA 107, 19163–19166 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

18. Selberg, J., Gomez, M. & Rolandi, M. The potential for convergence between synthetic biology and bioelectronics. Cell Syst. 7, 231–244 (2018).

    Article  CAS  PubMed  Google Scholar 

19. Rivnay, J. et al. Integrating bioelectronics with cell-based synthetic biology. Nat. Rev. Bioeng. 3, 317–332 (2025).

20. Aghlmand, F. et al. A 65-nm CMOS fluorescence sensor for dynamic monitoring of living cells. IEEE J. Solid-State Circuits 58, 3003–3019 (2023).

    Article  Google Scholar 

21. Lee, H., Liu, Y., Westervelt, R. M. & Ham, D. IC/microfluidic hybrid system for magnetic manipulation of biological cells. IEEE J. Solid-State Circuits 41, 1471–1480 (2006).

    Article  Google Scholar 

22. Ghafar-Zadeh, E., Sawan, M., Chodavarapu, V. P. & Hosseini-Nia, T. Bacteria growth monitoring through a differential CMOS capacitive sensor. IEEE Trans. Biomed. Circuits Syst. 4, 232–238 (2010).

    Article  PubMed  Google Scholar 

23. Manickam, A. et al. A fully integrated CMOS fluorescence biochip for DNA and RNA testing. IEEE J. Solid-State Circuits 52, 2857–2870 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

24. Zhu, C., Maldonado, J. & Sengupta, K. CMOS-based electrokinetic microfluidics with multi-modal cellular and bio-molecular sensing for end-to-end point-of-care system. IEEE Trans. Biomed. Circuits Syst. 15, 1250–1267 (2021).

    Article  PubMed  Google Scholar 

25. Inda-Webb, M. E. et al. Sub-1.4 cm³ capsule for detecting labile inflammatory biomarkers in situ. Nature 620, 386–392 (2023).

    Article  CAS  PubMed  Google Scholar 

26. Tschirhart, T. et al. Electronic control of gene expression and cell behaviour in Escherichia coli through redox signalling. Nat. Commun. 8, 14030 (2017).

27. Eddie, B. J., Malanoski, A. P., Onderko, E. L., Phillips, D. A. & Glaven, S. M. Marinobacter atlanticus electrode biofilms differentially regulate gene expression depending on electrode potential and lifestyle. Biofilm 3, 100051 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

28. Riglar, D. T. & Silver, P. A. Engineering bacteria for diagnostic and therapeutic applications. Nat. Rev. Microbiol. 16, 214–225 (2018).

    Article  CAS  PubMed  Google Scholar 

29. Rothschild, L. J. et al. Building synthetic cells—from the technology infrastructure to cellular entities. ACS Synth. Biol. 13, 974–997 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

30. Jung, J. K. et al. Cell-free biosensors for rapid detection of water contaminants. Nat. Biotechnol. 38, 1451–1459 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

31. Takahashi, M. K. et al. A low-cost paper-based synthetic biology platform for analyzing gut microbiota and host biomarkers. Nat. Commun. 9, 3347 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

32. Chen, Y. et al. Genetic circuit design automation for yeast. Nat. Microbiol. 5, 1349–1360 (2020).

    Article  CAS  PubMed  Google Scholar 

33. Fedorec, A. J. H. et al. Emergent digital bio-computation through spatial diffusion and engineered bacteria. Nat. Commun. 15, 4896 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

34. Sun, G. L., Reynolds, E. E. & Belcher, A. M. Designing yeast as plant-like hyperaccumulators for heavy metals. Nat. Commun. 10, 5080 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

35. van der Meer, J. R. & Belkin, S. Where microbiology meets microengineering: design and applications of reporter bacteria. Nat. Rev. Microbiol. 8, 511–522 (2010).

    Article  PubMed  Google Scholar 

36. Go´mez, R. et al. Microfluidic biochip for impedance spectroscopy of biological species. Biomed. Microdevices 3, 201–209 (2001).

    Google Scholar 

37. Petchakup, C., Li, K. & Hou, H. Advances in single cell impedance cytometry for biomedical applications. Micromachines 8, 87 (2017).

    Article  PubMed Central  Google Scholar 

38. Kang, J., Kim, T., Tak, Y., Lee, J.-H. & Yoon, J. Cyclic voltammetry for monitoring bacterial attachment and biofilm formation. J. Ind. Eng. Chem. 18, 800–807 (2012).

    Article  CAS  Google Scholar 

39. Zadeh, E. G., Sawan, M., Jalali, M. & Therriault, D. CMOS-based capacitive sensor array dedicated to microfluidic studies. In 2006 International Workshop on Computer Architecture for Machine Perception and Sensing 42–43 (IEEE, 2006).

40. Valijam, S. et al. Fabricating a dielectrophoretic microfluidic device using 3D-printed moulds and silver conductive paint. Sci. Rep. 13, 9560 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

41. Akabuogu, E. U., Zhang, L., Krašovec, R., Roberts, I. S. & Waigh, T. A. Electrical impedance spectroscopy with bacterial biofilms: neuronal-like behavior. Nano Lett. 24, 2234–2241 (2024).

    CAS  Google Scholar 

42. Arduini, F. et al. Origami multiple paper-based electrochemical biosensors for pesticide detection. Biosens. Bioelectron. 126, 346–354 (2019).

    Article  CAS  PubMed  Google Scholar 

43. Yi, C., Li, C.-W., Ji, S. & Yang, M. Microfluidics technology for manipulation and analysis of biological cells. Anal. Chim. Acta 560, 1–23 (2006).

    Article  CAS  Google Scholar 

44. Gach, P. C. et al. A droplet microfluidic platform for automating genetic engineering. ACS Synth. Biol. 5, 426–433 (2016).

    Article  CAS  PubMed  Google Scholar 

45. Iwai, K. et al. Scalable and automated CRISPR-based strain engineering using droplet microfluidics. Microsyst. Nanoeng. 8, 31 (2022).

    Article  CAS  Google Scholar 

46. Fu, A. Y., Spence, C., Scherer, A., Arnold, F. H. & Quake, S. R. A microfabricated fluorescence-activated cell sorter. Nat. Biotechnol. 17, 1109–1111 (1999).

    Article  CAS  PubMed  Google Scholar 

47. Hatch, A. C. et al. 1-Million droplet array with wide-field fluorescence imaging for digital PCR. Lab Chip 11, 3838–3845 (2011).

    Google Scholar 

48. Bhargava, K. C., Thompson, B. & Malmstadt, N. Discrete elements for 3D microfluidics. Proc. Natl Acad. Sci. USA 111, 15013–15018 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

49. Zeng, Y., Novak, R., Shuga, J., Smith, M. T. & Mathies, R. A. High-performance single cell genetic analysis using microfluidic emulsion generator arrays. Anal. Chem. 82, 3183–3190 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

50. Bennett, M. R. & Hasty, J. Microfluidic devices for measuring gene network dynamics in single cells. Nat. Rev. Genet. 10, 628–638 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

51. Toriello, N. M. et al. Integrated microfluidic bioprocessor for single-cell gene expression analysis. Proc. Natl Acad. Sci. USA 105, 20173–20178 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

52. Leung, K. et al. A programmable droplet-based microfluidic device applied to multiparameter analysis of single microbes and microbial communities. Proc. Natl Acad. Sci. USA 109, 7665–7670 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

53. Churski, K. et al. Rapid screening of antibiotic toxicity in an automated microdroplet system. Lab Chip 12, 1629–1637 (2012).

    Google Scholar 

54. Oblath, E. A., Henley, W. H., Alarie, J. P. & Ramsey, J. M. A microfluidic chip integrating DNA extraction and real-time PCR for the detection of bacteria in saliva. Lab Chip 13, 1325–1332 (2013).

    Google Scholar 

55. Lashkaripour, A. et al. Machine learning enables design automation of microfluidic flow-focusing droplet generation. Nat. Commun. 12, 25 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

56. Linshiz, G. et al. End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis. J. Biol. Eng. 10, 3 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

57. Fracassi, C., Postiglione, L., Fiore, G. & di Bernardo, D. Automatic control of gene expression in mammalian cells. ACS Synth. Biol. 5, 296–302 (2015).

    Article  PubMed  Google Scholar 

58. Wu, L. L., Babikian, S., Li, G.-P. & Bachman, M. Microfluidic printed circuit boards. In 2011 IEEE 61st Electronic Components and Technology Conference (ECTC) 1576–1581 (IEEE, 2011).

59. Husser, M. C., Vo, P. Q. N., Sinha, H., Ahmadi, F. & Shih, S. C. C. An automated induction microfluidics system for synthetic biology. ACS Synth. Biol. 7, 933–944 (2018).

    Article  CAS  PubMed  Google Scholar 

60. Howell, J., Hammarton, T. C., Altmann, Y. & Jimenez, M. High-speed particle detection and tracking in microfluidic devices using event-based sensing. Lab Chip 20, 3024–3035 (2020).

    CAS  Google Scholar 

61. de Cesare, I. et al. ChipSeg: an automatic tool to segment bacterial and mammalian cells cultured in microfluidic devices. ACS Omega 6, 2473–2476 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

62. Bachler, S., Haidas, D., Ort, M., Duncombe, T. A. & Dittrich, P. S. Microfluidic platform enables tailored translocation and reaction cascades in nanoliter droplet networks. Commun. Biol. 3, 769 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

63. van Sluijs, B., Maas, R. J. M., van der Linden, A. J., de Greef, T. F. A. & Huck, W. T. S. A microfluidic optimal experimental design platform for forward design of cell-free genetic networks. Nat. Commun. 13, 3626 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

64. Zhao, S. et al. A new design for living cell-based biosensors: microgels with a selectively permeable shell that can harbor bacterial species. Sens. Actuators B Chem. 334, 129648 (2021).

    Article  CAS  Google Scholar 

65. Khazim, M., Pedone, E., Postiglione, L., di Bernardo, D. & Marucci, L. A microfluidic/microscopy-based platform for on-chip controlled gene expression in mammalian cells. Methods Mol. Biol. 2229, 205–219 (2021).

66. Ren, Y. et al. A three-in-one microfluidic droplet digital PCR platform for absolute quantitative analysis of DNA. Lab Chip 23, 2521–2530 (2023).

    CAS  Google Scholar 

67. Sun, Y. et al. Two-layered microfluidic devices for high-throughput dynamic analysis of synthetic gene circuits in E. coli. ACS Synth. Biol. 11, 3954–3965 (2022).

    Article  CAS  PubMed  Google Scholar 

68. Rahman, K. M. T. & Butzin, N. C. Counter-on-chip for bacterial cell quantification, growth, and live–dead estimations. Sci. Rep. 14, 782 (2024).

69. Pardee, K. et al. Paper-based synthetic gene networks. Cell 159, 940–954 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

70. Dou, M., Dominguez, D. C., Li, X., Sanchez, J. & Scott, G. A versatile PDMS/paper hybrid microfluidic platform for sensitive infectious disease diagnosis. Anal. Chem. 86, 7978–7986 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

71. Delamarche, E., Juncker, D. & Schmid, H. Microfluidics for processing surfaces and miniaturizing biological assays. Adv. Mater. 17, 2911–2933 (2005).

    Article  CAS  Google Scholar 

72. Gulati, S. et al. Opportunities for microfluidic technologies in synthetic biology. J. R. Soc. Interface 6, S493–S506 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

73. Xian, Z. et al. A novel microfluidics PMMA/paper hybrid bioimmunosensor for laser-induced fluorescence detection in the determination of α-fetoprotein from serum. Microchem. J. 195, 109476 (2023).

    Article  CAS  Google Scholar 

74. Srinivasan, V., Pamula, V., Pollack, M. & Fair, R. A digital microfluidic biosensor for multianalyte detection. In the Sixteenth Annual International Conference on Micro Electro Mechanical Systems 327–330 (IEEE, 2003).

75. Hamedi, M. M. et al. Integrating electronics and microfluidics on paper. Adv. Mater. 28, 5054–5063 (2016).

    Article  CAS  PubMed  Google Scholar 

76. Lee, H., Sun, E., Ham, D. & Weissleder, R. Chip–NMR biosensor for detection and molecular analysis of cells. Nat. Med. 14, 869–874 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

77. Zhou, A. Y., Baruch, M., Ajo-Franklin, C. M. & Maharbiz, M. M. A portable bioelectronic sensing system (BESSY) for environmental deployment incorporating differential microbial sensing in miniaturized reactors. PLoS ONE 12, e0184994 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

78. Madhvapathy, S. R. et al. Miniaturized implantable temperature sensors for the long-term monitoring of chronic intestinal inflammation. Nat. Biomed. Eng. 8, 1040–1052 (2024).

79. Stephenson, A. et al. PurpleDrop: a digital microfluidics-based platform for hybrid molecular–electronics applications. IEEE Micro 40, 76–86 (2020).

    Article  Google Scholar 

80. Cai, R. et al. Creation of a point-of-care therapeutics sensor using protein engineering, electrochemical sensing and electronic integration. Nat. Commun. 15, 1689 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

81. Coelho, B. et al. Hybrid digital-droplet microfluidic chip for applications in droplet digital nucleic acid amplification: design, fabrication and characterization. Sensors 23, 4927 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

82. Bouzid, K., Greener, J., Carrara, S. & Gosselin, B. Portable impedance-sensing device for microorganism characterization in the field. Sci. Rep. 13, 10526 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

83. Jafari, H., Soleymani, L. & Genov, R. 16-Channel CMOS impedance spectroscopy DNA analyzer with dual-slope multiplying ADCs. IEEE Trans. Biomed. Circuits Syst. 6, 468–478 (2012).

    Article  Google Scholar 

84. Manaresi, N. et al. A CMOS chip for individual cell manipulation and detection. IEEE J. Solid-State Circuits 38, 2297–2305 (2003).

    Article  Google Scholar 

85. Luan, L., Evans, R. D., Jokerst, N. M. & Fair, R. B. Integrated optical sensor in a digital microfluidic platform. IEEE Sens. J. 8, 628–635 (2008).

    Article  CAS  Google Scholar 

86. Hunt, T. P., Issadore, D. & Westervelt, R. M. Integrated circuit/microfluidic chip to programmably trap and move cells and droplets with dielectrophoresis. Lab Chip 8, 81–87 (2008).

    CAS  Google Scholar 

87. Lai, K. Y.-T., Yang, Y.-T. & Lee, C.-Y. An intelligent digital microfluidic processor for biomedical detection. J. Signal Process. Syst. 78, 85–93 (2014).

    Article  Google Scholar 

88. Park, J. et al. Microscale biosensor array based on flexible polymeric platform toward lab-on-a-needle: real-time multiparameter biomedical assays on curved needle surfaces. ACS Sens. 5, 1363–1373 (2020).

    Article  CAS  PubMed  Google Scholar 

89. Khorasani, M., Behnam, M., van den Berg, L., Backhouse, C. J. & Elliott, D. G. High-voltage CMOS controller for microfluidics. IEEE Trans. Biomed. Circuits Syst. 3, 89–96 (2009).

    Article  CAS  PubMed  Google Scholar 

90. Issadore, D., Franke, T., Brown, K. A. & Westervelt, R. M. A microfluidic microprocessor: controlling biomimetic containers and cells using hybrid integrated circuit/microfluidic chips. Lab Chip 10, 2937–2943 (2010).

    Google Scholar 

91. Manickam, A., Chevalier, A., McDermott, M., Ellington, A. D. & Hassibi, A. A CMOS electrochemical impedance spectroscopy (EIS) biosensor array. IEEE Trans. Biomed. Circuits Syst. 4, 379–390 (2010).

    Article  PubMed  Google Scholar 

92. Bounik, R. et al. A CMOS microelectrode array integrated into an open, continuously perfused microfluidic system. In 2022 IEEE Biomedical Circuits and Systems Conference (BioCAS) 491–494 (IEEE, 2022).

93. Ding, Z., Xu, C., Wang, Y. & Pellegrini, G. Ultra-low-light CMOS biosensor complements microfluidics to achieve portable diagnostics. Procedia Technol. 27, 39–41 (2017).

    Article  Google Scholar 

94. Frey, U. et al. Switch-matrix-based high-density microelectrode array in CMOS technology. IEEE J. Solid-State Circuits 45, 467–482 (2010).

    Article  Google Scholar 

95. Liu, Q. et al. 17.7 Droplet microfluidics co-designed with real-time CMOS luminescence sensing and impedance spectroscopy of 4nl droplets at a 67mm/s velocity. In 2024 IEEE International Solid-State Circuits Conference (ISSCC) 326–328 (IEEE, 2024).

96. Jin, X., Liu, Z., Li, T., Guo, Q. & Yang, J. Online monitoring and portable analytical system with CMOS sensor and microfluidic technology for cell cultivation applications. In 2010 Symposium on Photonics and Optoelectronics 1–4 (IEEE, 2010).

97. Issadore, D., Franke, T., Brown, K. A., Hunt, T. P. & Westervelt, R. M. High-voltage dielectrophoretic and magnetophoretic hybrid integrated circuit/microfluidic chip. J. Microelectromech. Syst. 18, 1220–1225 (2009).

    Google Scholar 

98. Li, R. et al. A flexible and physically transient electrochemical sensor for real-time wireless nitric oxide monitoring. Nat. Commun. 11, 3207 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

99. Uguz, I. et al. Flexible switch matrix addressable electrode arrays with organic electrochemical transistor and pn diode technology. Nat. Commun. 15, 533 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

100. Sawan, M., Miled, M. A. & Ghafar-Zadeh, E. CMOS/microfluidic lab-on-chip for cells-based diagnostic tools. In 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology 5334–5337 (IEEE, 2010).

101. Cornelis, S. et al. Silicon µPCR chip for forensic STR profiling with hybeacon probe melting curves. Sci. Rep. 9, 7341 (2019).

102. Mimee, M. et al. An ingestible bacterial–electronic system to monitor gastrointestinal health. Science 360, 915–918 (2018).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

103. Lee, H., Liu, Y., Ham, D. & Westervelt, R. M. Integrated cell manipulation system—CMOS/microfluidic hybrid. Lab Chip 7, 331–337 (2007).

     CAS  Google Scholar 

104. Zhou, Q. et al. Miniature magnetic resonance imaging system for in situ monitoring of bacterial growth and biofilm formation. In IEEE Transactions on Biomedical Circuits and Systems 990–1000 (IEEE, 2024).

105. Hall, D. A. et al. A scalable CMOS molecular electronics chip for single-molecule biosensing. IEEE Trans. Biomed. Circuits Syst. 16, 1030–1043 (2022).

     Article  PubMed  Google Scholar 

106. Huang, Y. & Mason, A. J. Lab-on-CMOS integration of microfluidics and electrochemical sensors. Lab Chip 13, 3929–3934 (2013).

     Google Scholar 

107. Ghafar-Zadeh, E., Sawan, M. & Therriault, D. Novel direct-write CMOS-based laboratory-on-chip: design, assembly and experimental results. Sens. Actuators A Phys. 134, 27–36 (2007).

     Article  CAS  Google Scholar 

108. Lee, H., Xu, L., Koh, D., Nyayapathi, N. & Oh, K. Various on-chip sensors with microfluidics for biological applications. Sensors 14, 17008–17036 (2014).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

109. Toumazou, C. et al. Simultaneous DNA amplification and detection using a pH-sensing semiconductor system. Nat. Methods 10, 641–646 (2013).

     Article  CAS  PubMed  Google Scholar 

110. Chien, J.-C. et al. A high-throughput flow cytometry-on-a-CMOS platform for single-cell dielectric spectroscopy at microwave frequencies. Lab Chip 18, 2065–2076 (2018).

     CAS  Google Scholar 

111. Levine, P. M., Gong, P., Levicky, R. & Shepard, K. L. Active CMOS sensor array for electrochemical biomolecular detection. IEEE J. Solid-State Circuits 43, 1859–1871 (2008).

     Article  Google Scholar 

112. Rosenstein, J. K., Wanunu, M., Merchant, C. A., Drndic, M. & Shepard, K. L. Integrated nanopore sensing platform with sub-microsecond temporal resolution. Nat. Methods 9, 487–492 (2012).

     Article  CAS  PubMed  Google Scholar 

113. Hong, L., Li, H., Yang, H. & Sengupta, K. Fully integrated fluorescence biosensors on-chip employing multi-functional nanoplasmonic optical structures in CMOS. IEEE J. Solid-State Circuits 52, 2388–2406 (2017).

     Article  Google Scholar 

114. Zhu, C., Wen, Y., Liu, T., Yang, H. & Sengupta, K. An ingestible pill with CMOS fluorescence sensor array, bi-directional wireless interface and packaged optics for in-vivo bio-molecular sensing. IEEE Trans. Biomed. Circuits Syst. 17, 257–272 (2023).

     Article  PubMed  Google Scholar 

115. Bustillo, J., Fife, K., Merriman, B. & Rothberg, J. Development of the ion torrent CMOS chip for DNA sequencing. In 2013 IEEE International Electron Devices Meeting 8.1.1–8.1.4 (IEEE, 2013).

116. Lai, K. Y.-T. et al. A field-programmable lab-on-a-chip with built-in self-test circuit and low-power sensor-fusion solution in 0.35μm standard CMOS process. In 2015 IEEE Asian Solid-State Circuits Conference (A-SSCC) 1–4 (IEEE, 2015).

117. Murali, P. et al. 24.6 A CMOS micro-flow cytometer for magnetic label detection and classification. In 2014 IEEE International Solid-State Circuits Conference Digest of Technical Papers (ISSCC) 422–423 (IEEE, 2014).

118. Singh, R. R., Leng, L., Guenther, A. & Genov, R. A CMOS–microfluidic chemiluminescence contact imaging microsystem. IEEE J. Solid-State Circuits 47, 2822–2833 (2012).

     Article  Google Scholar 

119. Kumashi, S. et al. A CMOS multi-modal electrochemical and impedance cellular sensing array for massively paralleled exoelectrogen screening. IEEE Trans. Biomed. Circuits Syst. 15, 221–234 (2021).

     Article  PubMed  Google Scholar 

120. Lee, D. et al. A multi-functional CMOS biosensor array with on-chip DEP-assisted sensing for rapid low-concentration analyte detection and close-loop particle manipulation with no external electrodes. IEEE Trans. Biomed. Circuits Syst. 17, 1214–1226 (2023).

     Article  PubMed  Google Scholar 

121. Kuo, Y.-H., Chen, Y.-S., Huang, P.-C. & Lee, G.-B. A CMOS-based capacitive biosensor for detection of a breast cancer microRNA biomarker. IEEE Open J. Nanotechnol. 1, 157–162 (2020).

     Article  Google Scholar 

122. Murari, K., Etienne-Cummings, R., Thakor, N. V. & Cauwenberghs, G. A CMOS in-pixel CTIA high-sensitivity fluorescence imager. IEEE Trans. Biomed. Circuits Syst. 5, 449–458 (2011).

     Article  PubMed  PubMed Central  Google Scholar 

123. Forouhi, S., Dehghani, R. & Ghafar-Zadeh, E. CMOS based capacitive sensors for life science applications: a review. Sens. Actuators A Phys. 297, 111531 (2019).

     Article  CAS  Google Scholar 

124. Vallero, A. et al. Memristive biosensors integration with microfluidic platform. IEEE Trans. Circuits Syst. I Regul. Pap. 63, 2120–2127 (2016).

     Article  Google Scholar 

125. Sun, A. C., Alvarez-Fontecilla, E., Venkatesh, A. G., Aronoff-Spencer, E. & Hall, D. A. High-density redox amplified coulostatic discharge-based biosensor array. IEEE J. Solid-State Circuits 53, 2054–2064 (2018).

     Article  PubMed  PubMed Central  Google Scholar 

126. Tang, H. et al. 2D magnetic sensor array for real-time cell tracking and multi-site detection with increased robustness and flow-rate. In 2019 IEEE Custom Integrated Circuits Conference (CICC) 1–4 (IEEE, 2019).

127. Spyropoulos, G. D., Gelinas, J. N. & Khodagholy, D. Internal ion-gated organic electrochemical transistor: a building block for integrated bioelectronics. Sci. Adv. 5, eaau7378 (2019).

128. Linder, V. et al. Microfluidics/CMOS orthogonal capabilities for cell biology. Biomed. Microdevices 8, 159–166 (2006).

     Google Scholar 

129. Atkinson, J. T. et al. Real-time bioelectronic sensing of environmental contaminants. Nature 611, 548–553 (2022).

     Article  CAS  PubMed  Google Scholar 

130. Hall, D. A., Gaster, R. S., Makinwa, K. A. A., Wang, S. X. & Murmann, B. A 256 pixel magnetoresistive biosensor microarray in 0.18 µm CMOS. IEEE J. Solid-State Circuits 48, 1290–1301 (2013).

     Article  PubMed  PubMed Central  Google Scholar 

131. Fuller, C. W. et al. Molecular electronics sensors on a scalable semiconductor chip: a platform for single-molecule measurement of binding kinetics and enzyme activity. Proc. Natl Acad. Sci. USA 119, e2112812119 (2022).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

132. Manickam, A. et al. A fully-electronic charge-based DNA sequencing CMOS biochip. In 2012 Symposium on VLSI Circuits (VLSIC) 126–127 (IEEE, 2012).

133. Manickam, A. et al. A CMOS electrochemical biochip with 32 × 32 three-electrode voltammetry pixels. IEEE J. Solid-State Circuits 54, 2980–2990 (2019).

     Article  Google Scholar 

134. Dragas, J. et al. In vitro multi-functional microelectrode array featuring 59760 electrodes, 2048 electrophysiology channels, stimulation, impedance measurement, and neurotransmitter detection channels. IEEE J. Solid-State Circuits 52, 1576–1590 (2017).

     Article  PubMed  PubMed Central  Google Scholar 

135. Rothe, J., Frey, O., Stettler, A., Chen, Y. & Hierlemann, A. Fully integrated CMOS microsystem for electrochemical measurements on 32 × 32 working electrodes at 90 frames per second. Anal. Chem. 86, 6425–6432 (2014).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

136. Wang, H., Mahdavi, A., Tirrell, D. A. & Hajimiri, A. A magnetic cell-based sensor. Lab Chip 12, 4465–4471 (2012).

     Google Scholar 

137. Lee, D. et al. 17.6 Fully integrated CMOS ferrofluidic biomolecular processing platform with on-chip droplet-based manipulation, multiplexing and sensing. In 2024 IEEE International Solid-State Circuits Conference (ISSCC) 324–326 (IEEE, 2024).

138. Hierlemann, A., Frey, U., Hafizovic, S. & Heer, F. Growing cells atop microelectronic chips: interfacing electrogenic cells in vitro with CMOS-based microelectrode arrays. Proc. IEEE 99, 252–284 (2011).

     Article  CAS  Google Scholar 

139. Welch, D. & Christen, J. B. Seamless integration of CMOS and microfluidics using flip chip bonding. J. Micromech. Microeng. 23, 035009 (2013).

     Article  CAS  Google Scholar 

140. Dong, R., Liu, Y., Mou, L., Deng, J. & Jiang, X. Microfluidics‐based biomaterials and biodevices. Adv. Mater. 31, e1805033 (2018).

141. van Erp, R., Soleimanzadeh, R., Nela, L., Kampitsis, G. & Matioli, E. Co-designing electronics with microfluidics for more sustainable cooling. Nature 585, 211–216 (2020).

     Article  PubMed  Google Scholar 

142. Sun, T. & Morgan, H. Single-cell microfluidic impedance cytometry: a review. Microfluid. Nanofluid. 8, 423–443 (2010).

     Article  CAS  Google Scholar 

143. Ostrov, N. et al. A modular yeast biosensor for low-cost point-of-care pathogen detection. Sci. Adv. 3, e1603221 (2017).

     Article  PubMed  PubMed Central  Google Scholar 

144. Carpenter, A. C., Paulsen, I. T. & Williams, T. C. Blueprints for biosensors: design, limitations, and applications. Genes 9, 375 (2018).

     Article  PubMed  PubMed Central  Google Scholar 

145. Au, A. K., Bhattacharjee, N., Horowitz, L. F., Chang, T. C. & Folch, A. 3D-printed microfluidic automation. Lab Chip 15, 1934–1941 (2015).

     CAS  Google Scholar 

146. Paguirigan, A. L. & Beebe, D. J. Microfluidics meet cell biology: bridging the gap by validation and application of microscale techniques for cell biological assays. BioEssays 30, 811–821 (2008).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

147. Yan, S., Zhang, J., Yuan, D. & Li, W. Hybrid microfluidics combined with active and passive approaches for continuous cell separation. Electrophoresis 38, 238–249 (2016).

     Article  PubMed  Google Scholar 

148. Battat, S., Weitz, D. A. & Whitesides, G. M. An outlook on microfluidics: the promise and the challenge. Lab Chip 22, 530–536 (2022).

     CAS  Google Scholar 

149. Atkinson, J. T., Chavez, M. S., Niman, C. M. & El‐Naggar, M. Y. Living electronics: a catalogue of engineered living electronic components. Microb. Biotechnol. 16, 507–533 (2022).

     Article  PubMed  PubMed Central  Google Scholar 

150. Diorio, C., Hsu, D. & Figueroa, M. Adaptive CMOS: from biological inspiration to systems-on-a-chip. Proc. IEEE 90, 345–357 (2002).

     Article  Google Scholar 

151. Mosadegh, B., Bersano-Begey, T., Park, J. Y., Burns, M. A. & Takayama, S. Next-generation integrated microfluidic circuits. Lab Chip 11, 2813–2818 (2011).

     Google Scholar 

152. Lashkaripour, A., Silva, R. & Densmore, D. Desktop micromilled microfluidics. Microfluid. Nanofluid. 22, 31 (2018).

153. Khan, S. M., Gumus, A., Nassar, J. M. & Hussain, M. M. CMOS enabled microfluidic systems for healthcare based applications. Adv. Mater. 30, e1705759 (2018).

     Article  PubMed  Google Scholar 

154. Karim, A. S. et al. Deconstructing synthetic biology across scales: a conceptual approach for training synthetic biologists. Nat. Commun. 15, 5425 (2024).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

155. Ma, Y. et al. A review of electrochemical electrodes and readout interface designs for biosensors. IEEE Open J. Solid-State Circuits Soc. 3, 76–88 (2023).

     Article  Google Scholar 

156. Dixon, T. A., Williams, T. C. & Pretorius, I. S. Sensing the future of bio-informational engineering. Nat. Commun. 12, 388 (2021).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

157. Datta-Chaudhuri, T., Smela, E. & Abshire, P. A. System-on-chip considerations for heterogeneous integration of CMOS and fluidic bio-interfaces. IEEE Trans. Biomed. Circuits Syst. 10, 1129–1142 (2016).

     Article  PubMed  Google Scholar 

158. Brooks, S. M. & Alper, H. S. Applications, challenges, and needs for employing synthetic biology beyond the lab. Nat. Commun. 12, 1390 (2021).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

159. Steiger, C. et al. Ingestible electronics for diagnostics and therapy. Nat. Rev. Mater. 4, 83–98 (2018).

     Article  Google Scholar 

160. Nadeau, P. et al. Prolonged energy harvesting for ingestible devices. Nat. Biomed. Eng. 1, 0022 (2017).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

161. Muluneh, M. & Issadore, D. A multi-scale PDMS fabrication strategy to bridge the size mismatch between integrated circuits and microfluidics. Lab Chip 14, 4552–4558 (2014).

     CAS  Google Scholar 

162. Zargaryan, A., Farhoudi, N., Haworth, G., Ashby, J. F. & Au, S. H. Hybrid 3D printed-paper microfluidics. Sci. Rep. 10, 18379 (2020).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

163. Huang, H. & Densmore, D. Fluigi. ACM J. Emerg. Technol. Comput. Syst. 11, 1–19 (2014).

     Article  Google Scholar 

164. Kim, S. J. et al. The bottom of the memory hierarchy: semiconductor and DNA data storage. MRS Bull. 48, 547–559 (2023).

     Article  Google Scholar 

165. Ros, P. M., Miccoli, B., Sanginario, A. & Demarchi, D. Low-power architecture for integrated CMOS bio-sensing. In 2017 IEEE Biomedical Circuits and Systems Conference (BioCAS) 1–4 (IEEE, 2017).

166. Perry, J. M., Soffer, G., Jain, R. & Shih, S. C. C. Expanding the limits towards ‘one-pot’ DNA assembly and transformation on a rapid-prototype microfluidic device. Lab Chip 21, 3730–3741 (2021).

     CAS  Google Scholar 

167. Ahrar, S., Raje, M., Lee, I. C. & Hui, E. E. Pneumatic computers for embedded control of microfluidics. Sci. Adv. 9, eadg0201 (2023).

     Article  PubMed  PubMed Central  Google Scholar 

168. Iyer, V., Murali, P., Paredes, J., Liepmann, D. & Boser, B. Encapsulation of integrated circuits in plastic microfluidic systems using hot embossing. In 2015 Transducers — 2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS) 1822–1825 (IEEE, 2015).

169. Gopinathan, K. A., Mishra, A., Mutlu, B. R., Edd, J. F. & Toner, M. A microfluidic transistor for automatic control of liquids. Nature 622, 735–741 (2023).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

170. Jang, B. & Hassibi, A. Biosensor systems in standard CMOS processes: fact or fiction? In 2008 IEEE International Symposium on Industrial Electronics 2045–2050 (IEEE, 2008).

171. Singh, R., Manickam, A. & Hassibi, A. CMOS biochips for hypothesis-driven DNA analysis. In 2014 IEEE Biomedical Circuits and Systems Conference (BioCAS) Proceedings 484–487 (IEEE, 2014).

172. Olanrewaju, A., Beaugrand, M., Yafia, M. & Juncker, D. Capillary microfluidics in microchannels: from microfluidic networks to capillaric circuits. Lab Chip 18, 2323–2347 (2018).

     CAS  Google Scholar 

173. Li, J., Ha, N. S., ‘Leo’ Liu, T., van Dam, R. M. & Kim, C.-J. ‘C. J. ’ Ionic-surfactant-mediated electro-dewetting for digital microfluidics. Nature 572, 507–510 (2019).

     Article  CAS  PubMed  Google Scholar 

174. Pollack, M. G., Shenderov, A. D. & Fair, R. B. Electrowetting-based actuation of droplets for integrated microfluidics. Lab Chip 2, 96 (2002).

175. Moragues, T. et al. Droplet-based microfluidics. Nat. Rev. Methods Primers 3, 32 (2023).

176. Ding, Y., Howes, P. D. & deMello, A. J. Recent advances in droplet microfluidics. Anal. Chem. 92, 132–149 (2019).

     Article  PubMed  Google Scholar 

177. Lenshof, A. & Laurell, T. Continuous separation of cells and particles in microfluidic systems. Chem. Soc. Rev. 39, 1203–1217 (2010).

     Article  PubMed  Google Scholar 

178. Beebe, D. J., Mensing, G. A. & Walker, G. M. Physics and applications of microfluidics in biology. Annu. Rev. Biomed. Eng. 4, 261–286 (2002).

     Article  CAS  PubMed  Google Scholar 

179. Nielsen, J. B. et al. Microfluidics: innovations in materials and their fabrication and functionalization. Anal. Chem. 92, 150–168 (2019).

     Article  PubMed  PubMed Central  Google Scholar 

180. Tsur, E. E. Computer-aided design of microfluidic circuits. Annu. Rev. Biomed. Eng. 22, 285–307 (2020).

     Article  CAS  PubMed  Google Scholar 

181. Sanka, R., Lippai, J., Samarasekera, D., Nemsick, S. & Densmore, D. 3DμF — interactive design environment for continuous flow microfluidic devices. Sci. Rep. 9, 9166 (2019).

     Article  PubMed  PubMed Central  Google Scholar 

182. Squires, T. M. & Quake, S. R. Microfluidics: fluid physics at the nanoliter scale. Rev. Mod. Phys. 77, 977–1026 (2005).

     Article  CAS  Google Scholar 

183. Sackmann, E. K., Fulton, A. L. & Beebe, D. J. The present and future role of microfluidics in biomedical research. Nature 507, 181–189 (2014).

     Article  CAS  PubMed  Google Scholar 

184. Liu, Q. et al. A threshold-based bioluminescence detector with a CMOS-integrated photodiode array in 65 nm for a multi-diagnostic ingestible capsule. IEEE J. Solid-State Circuits 58, 838–851 (2023).

     Article  Google Scholar 

185. Gregor, C., Gwosch, K. C., Sahl, S. J. & Hell, S. W. Strongly enhanced bacterial bioluminescence with the ilux operon for single-cell imaging. Proc. Natl Acad. Sci. USA 115, 962–967 (2018).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

186. Ying, D. & Hall, D. A. Current sensing front-ends: a review and design guidance. IEEE Sens. J. 21, 22329–22346 (2021).

     Article  Google Scholar 

187. Mulleti, S., Bhandari, A. & Eldar, Y. C. Power-aware analog to digital converters. In Applied and Numerical Harmonic Analysis 415–452 (Birkhäuser, 2023).

188. Yasar, A. & Yazicigil, R. T. Physical-layer security for energy-constrained integrated systems: challenges and design perspectives. IEEE Open J. Solid-State Circuits Soc. 3, 262–273 (2023).

     Article  Google Scholar 

189. De la Paz, E. et al. A self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites. Nat. Commun. 13, 7405 (2022).

     Article  PubMed  PubMed Central  Google Scholar 

190. Chandrakasan, A. P., Verma, N. & Daly, D. C. Ultralow-power electronics for biomedical applications. Annu. Rev. Biomed. Eng. 10, 247–274 (2008).

     Article  CAS  PubMed  Google Scholar 

191. Mercier, P. P., Lysaght, A. C., Bandyopadhyay, S., Chandrakasan, A. P. & Stankovic, K. M. Energy extraction from the biologic battery in the inner ear. Nat. Biotechnol. 30, 1240–1243 (2012).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

192. Wang, A., Highsmith Calhoun, B., & Chandrakasan, A. P. Sub-threshold design for ultra low-power systems. In Series on Integrated Circuits and Systems (Springer, 2006).

193. Farrar, J. T., Berkley, C. & Zworykin, V. K. Telemetering of intraenteric pressure in man by an externally energized wireless capsule. Science 131, 1814 (1960).

     Article  CAS  PubMed  Google Scholar 

194. Yeknami, A. F. et al. A 0.3-V CMOS biofuel-cell-powered wireless glucose/lactate biosensing system. IEEE J. Solid-State Circuits 53, 3126–3139 (2018).

     Article  Google Scholar 

195. Dong, K. et al. Microbial fuel cell as power supply for implantable medical devices: a novel configuration design for simulating colonic environment. Biosens. Bioelectron. 41, 916–919 (2013).

     Article  CAS  PubMed  Google Scholar 

196. El-Damak, D. & Chandrakasan, A. P. Solar energy harvesting system with integrated battery management and startup using single inductor and 3.2nW quiescent power. In 2015 Symposium on VLSI Circuits (VLSI Circuits) C280–C281 (IEEE, 2015).

197. Kadirvel, K. et al. A 330nA energy-harvesting charger with battery management for solar and thermoelectric energy harvesting. In 2012 IEEE International Solid-State Circuits Conference – (ISSCC) 106–108 (IEEE, 2012).

198. Ramadass, Y. K. & Chandrakasan, A. P. A batteryless thermoelectric energy-harvesting interface circuit with 35mV startup voltage. In 2010 IEEE International Solid-State Circuits Conference — (ISSCC) 486–487 (IEEE, 2010).

199. Dagdeviren, C. et al. Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm. Proc. Natl Acad. Sci. USA 111, 1927–1932 (2014).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

200. Sadat Mousavi, P. et al. A multiplexed, electrochemical interface for gene-circuit-based sensors. Nat. Chem. 12, 48–55 (2019).

     Article  PubMed  Google Scholar 

201. Amalfitano, E. et al. A glucose meter interface for point-of-care gene circuit-based diagnostics. Nat. Commun. 12, 724 (2021).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

202. Sang, M., Kim, K., Shin, J. & Yu, K. J. Ultra‐thin flexible encapsulating materials for soft bio‐integrated electronics. Adv. Sci. 9, e2202980 (2022).

     Article  Google Scholar 

203. Yang, Y. & Gao, W. Wearable and flexible electronics for continuous molecular monitoring. Chem. Soc. Rev. 48, 1465–1491 (2019).

     Article  CAS  PubMed  Google Scholar 

204. Iyer, V., Issadore, D. A. & Aflatouni, F. The next generation of hybrid microfluidic/integrated circuit chips: recent and upcoming advances in high-speed, high-throughput, and multifunctional lab-on-IC systems. Lab Chip 23, 2553–2576 (2023).

     CAS  Google Scholar 

205. McClune, C. J., Alvarez-Buylla, A., Voigt, C. A. & Laub, M. T. Engineering orthogonal signalling pathways reveals the sparse occupancy of sequence space. Nature 574, 702–706 (2019).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

206. Du, P. et al. De novo design of an intercellular signaling toolbox for multi-channel cell–cell communication and biological computation. Nat. Commun. 11, 4226 (2020).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

207. Marken, J. P. & Murray, R. M. Addressable and adaptable intercellular communication via DNA messaging. Nat. Commun. 14, 2358 (2023).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

208. Sexton, J. T. & Tabor, J. J. Multiplexing cell–cell communication. Mol. Syst. Biol. 16, e9618 (2020).

     Article  PubMed  PubMed Central  Google Scholar 

209. LaFleur, T. L., Hossain, A. & Salis, H. M. Automated model-predictive design of synthetic promoters to control transcriptional profiles in bacteria. Nat. Commun. 13, 5159 (2022).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

210. Sun, M. G. F., Seo, M.-H., Nim, S., Corbi-Verge, C. & Kim, P. M. Protein engineering by highly parallel screening of computationally designed variants. Sci. Adv. 2, e1600692 (2016).

     Article  PubMed  PubMed Central  Google Scholar 

211. Roehner, N. et al. GOLDBAR: a framework for combinatorial biological design. ACS Synth. Biol. 13, 2899–2911 (2024).

     Article  CAS  PubMed  Google Scholar 

212. Naseri, G. & Koffas, M. A. G. Application of combinatorial optimization strategies in synthetic biology. Nat. Commun. 11, 2446 (2020).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

213. Salahuddin, S., Ni, K. & Datta, S. The era of hyper-scaling in electronics. Nat. Electron. 1, 442–450 (2018).

     Article  Google Scholar 

214. Castle, S. D., Stock, M. & Gorochowski, T. E. Engineering is evolution: a perspective on design processes to engineer biology. Nat. Commun. 15, 3640 (2024).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

215. Oliveira, S. M. D. & Densmore, D. Hardware, software, and wetware codesign environment for synthetic biology. Biodes. Res. 2022, 9794510 (2022).

216. Yazicigil, R. T. et al. Beyond crypto: physical-layer security for internet of things devices. IEEE Solid-State Circuits Mag. 12, 66–78 (2020).

     Article  Google Scholar 

217. Vakhter, V., Soysal, B., Schaumont, P. & Guler, U. Threat modeling and risk analysis for miniaturized wireless biomedical devices. IEEE Internet Things J. 9, 13338–13352 (2022).

     Google Scholar 

218. Vatambeti, R. et al. Prediction of DDoS attacks in Agriculture 4.0 with the help of prairie dog optimization algorithm with IDSNet. Sci. Rep. 13, 15371 (2023).

     Article  CAS  PubMed  PubMed Central  Google Scholar 

219. Maraveas, C., Rajarajan, M., Arvanitis, K. G. & Vatsanidou, A. Cybersecurity threats and mitigation measures in Agriculture 4.0 and 5.0. Smart Agric. Technol. 9, 100616 (2024).

     Google Scholar 

220. Rettore de Araujo Zanella, A., da Silva, E. & Pessoa Albini, L. C. Security challenges to smart agriculture: current state, key issues, and future directions. Array 8, 100048 (2020).

     Article  Google Scholar 

Download references