A micro-array bio detection system based on a GMR sensor with 50-ppm sensitivity

Abstract

Bio detection is widely utilized in hospitals and laboratories. However, conventional bio detection methods suffer from long detection time, complex operation, and low sensitivity, and these issues prevent their use in point of care testing (POCT) applications. Microelectronic bio detection methods are proposed to overcome these issues. Bio detection based on a micro-electronic technique allows easy integration of a system, leading to a fast detection speed and simple operation. In this work, a fully microelectronic bio detection system including a sensor design, a read-out strategy, and data processing is proposed based on a GMR biosensor. A GMR sensor chip is designed and different passivation layer thicknesses are tested to improve sensitivity. A 40 nm thickness passivation is realized to produce the largest response without oxidization and breakdown. In order to integrate the read-out circuit and simplify operations, a 4-channel read-out biochip is designed and fabricated, and this exhibits a super-low output noise corresponding to −116.84 dBm/Hz at the operation frequency. This means that the noise only approximately corresponds to the signal level of five magnetic nanoparticles with a diameter of 200 nm. A reference sensor is also utilized to cancel the unwanted signal and reduce common-mode noise and error to improve sensitivity. Measurements indicate that 90% suppression is achieved. The measurements also reveal that a sensitivity of 50 ppm is achieved with the proposed GMR bio detection system.

This is a preview of subscription content, access via your institution.

References

  1. 1

    Lequin R M. Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). Clin Chem, 2005, 51: 2415–2418

    Article  Google Scholar 

  2. 2

    Leng S X, McElhaney J E, Walston J D, et al. ELISA and multiplex technologies for cytokine measurement in inflammation and aging research. J Gerontol Ser A-Biol Sci Med Sci, 2008, 63: 879–884

    Article  Google Scholar 

  3. 3

    Weiss S. Fluorescence spectroscopy of single biomolecules. Science, 1999, 283: 1676–1683

    Article  Google Scholar 

  4. 4

    Yazawa Y, Oonishi T, Watanabe K, et al. A wireless biosensing chip for DNA detection. In: Digest of Technical Papers of IEEE International Solid-State Circuits Conference (ISSCC), 2005. 562–617

    Google Scholar 

  5. 5

    Garner D M, Bai H, Georgiou P, et al. A multichannel DNA SoC for rapid point-of-care gene detection. In: Digest of Technical Papers of IEEE International Solid-State Circuits Conference (ISSCC), 2010. 492–493

    Google Scholar 

  6. 6

    Wang Z, Miao J, Xu T, et al. Biosensors based on flexural mode piezo-diaphragm. In: Proceedings of the 3rd IEEE International Conference on Nano/Micro Engineered and Molecular Systems (NEMS), Sanya, 2008. 374–378

    Google Scholar 

  7. 7

    Zhang L, He X Q, Wang Y, et al. A fully integrated CMOS nanoscale biosensor microarray. In: Proceedings of IEEE Custom Integrated Circuits Conference (CICC), San Jose, 2011. 1–4

    Google Scholar 

  8. 8

    Manickam A, Chevalier A, McDermott M, et al. A CMOS electrochemical impedance spectroscopy (EIS) biosensor array. IEEE Trans Biomed Circuits Syst, 2010, 4: 379–390

    Article  Google Scholar 

  9. 9

    Skucha K, Liu P, Megens M, et al. A compact hall-effect sensor array for the detection and imaging of single magnetic bead in biomedical assay. In: Proceedings of the 16th International Solid-State Sensors, Actuators and Microsystems Conference, Beijing, 2011. 1833–1836

    Google Scholar 

  10. 10

    Besse P, Boero G, Demierre M, et al. Detection of a single magnetic microbead using a miniaturized silicon Hall sensor. Appl Phys Lett, 2002, 80: 4199–4201

    Article  Google Scholar 

  11. 11

    Wang H, Chen Y, Hassibi A, et al. A frequency-shift CMOS magnetic biosensor array with signle-bead sensitibity and no external magnet. In: Digest of Technical Papers of IEEE International Solid-State Circuits Conference (ISSCC), 2009. 438–439

    Google Scholar 

  12. 12

    Koets M, van der Wijk T, van Eemerena J T W M, et al. Rapid DNA multi-analyte immunoassay on a magneto-resistance biosensor. Biosens Bioelectron, 2009, 24: 1893–1898

    Article  Google Scholar 

  13. 13

    Han S J, Xu L, Yu H, et al. CMOS integrated DNA microarray based on GMR sensor. In: Proceedings of International Electron Devices Meeting (IEDM’06), San Francisco, 2006. 11–13

    Google Scholar 

  14. 14

    de Boer B M, Kahlman J A H M, Jansen T P G H, et al. An integrated and sensitive detection platform for magneto- resistive biosensors. Biosens Bioelectron, 2007, 22: 2366–2370

    Article  Google Scholar 

  15. 15

    Hall D A, Gaster R S, Osterfeld S J, et al. A 256 channel magnetoresistive biosensor microarray for quantitative proteomics. In: Proceedings of 2011 Symposium on VLSI Circuits (VLSIC), Honolulu, 2011. 174–175

    Google Scholar 

  16. 16

    Hall D A, Gaster R S, Osterfeld S J, et al. GMR biosensor arrays: correction techniques for reproducibility and enhanced sensitivity. Biosens Bioelectron, 2010, 25: 2177–2181

    Article  Google Scholar 

  17. 17

    Hall D A, Gaster R S, Makinwa K A A, et al. A 256 Pixel Magnetoresistive Biosensor Microarray in 0.18µm CMOS. IEEE J Solid-State Circ, 2013, 48: 1290–1301

    Article  Google Scholar 

  18. 18

    Rife J C, Miller M M, Sheehan P E, et al. Design and performance of GMR sensor for the detection of magnetic microbeads in biosensors. Sensor Actuator A-Phys, 2003, 107: 209–218

    Article  Google Scholar 

  19. 19

    Wang H. Magnetic sensors for diagnostic medicine: CMOS-based magnetic particle detectors for medical diagnosis applications. Microw Mag, 2013, 14: 110–130

    Article  Google Scholar 

  20. 20

    Skucha K, Gambini S, Liu P, et al. Design considerations for CMOS-integrated Hall-effect magnetic bead detectors for biosensor applications. J Microelectromech Syst, 2013, 22: 1327–1338

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation of China (Grant Nos. 61204026, 61101001, 61674087), Guangdong’s High-Tech Project (Grant No. 2015B020233001), Dongguan’s High-Tech Project (Grant No. 2014215102), and Tsinghua University Initiative Scientific Research Program.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Lei Zhang.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhu, C., Zhang, L., Geng, J. et al. A micro-array bio detection system based on a GMR sensor with 50-ppm sensitivity. Sci. China Inf. Sci. 60, 082403 (2017). https://doi.org/10.1007/s11432-016-0645-2

Download citation

Keywords

  • giant magnetoresistance (GMR)
  • biosensor
  • magnetic nanoparticle (MNP)
  • small signal extraction
  • sensitivity