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A portable battery powered microfluidic impedance cytometer with smartphone readout: towards personal health monitoring

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Abstract

We present a portable system for personalized blood cell counting consisting of a microfluidic impedance cytometer and portable analog readout electronics, feeding into an analog-to-digital converter (ADC), and being transmitted via Bluetooth to a user-accessible mobile application. We fabricated a microfluidic impedance cytometer with a novel portable analog readout. The novel design of the analog readout, which consists of a lock-in-amplifier followed by a high-pass filter stage for subtraction of drift and DC offset, and a post-subtraction high gain stage, enables detection of particles and cells as small as 1 μm in diameter, despite using a low-end 8-bit ADC. The lock-in-amplifier and the ADC were set up to receive and transmit data from a Bluetooth module. In order to initiate the system, as well as to transmit all of the data, a user friendly mobile application was developed, and a proof-of-concept trial was run on a blood sample. Applications such as personalized health monitoring require robust device operation and resilience to clogging. It is desirable to avoid using channels comparable in size to the particles being detected thus requiring high levels of sensitivity. Despite using low-end off-the-shelf hardware, our sensing platform was capable of detecting changes in impedance as small as 0.032%, allowing detection of 3 μm diameter particles in a 300 μm wide channel. The sensitivity of our system is comparable to that of a high-end bench-top impedance spectrometer when tested using the same sensors. The novel analog design allowed for an instrument with a footprint of less than 80 cm2. The aim of this work is to demonstrate the potential of using microfluidic impedance spectroscopy for low cost health monitoring. We demonstrated the utility of the platform technology towards cell counting, however, our platform is broadly applicable to assaying wide panels of biomarkers including proteins, nucleic acids, and various cell types.

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References

  • C. Azzolini, A. Magnanini, M. Tonelli, G. Chiorboli, C. Morandi, Integrated lock-in amplifier for contactless interface to magnetically stimulated mechanical resonators. Design and Technology of Integrated Systems in Nanoscale Era, 2008. DTIS 2008. 3rd International Conference on, pp. 1–6, 2008.

  • L.E. Bengtsson, A microcontroller-based lock-in amplifier for sub-milliohm resistance measurements. Rev. Sci. Instrum. 075103, 1–8 (2012)

    Google Scholar 

  • F.C. Bo, Y.M. Li, The digital lock-in amplifier for detecting the power traveling wave signal TT. Int. J. Signal Process. Image Process. Pattern Recognit 8(4), 361–374 (2015)

    Google Scholar 

  • A. D’Amico, A. De Marcellis, C. Di Carlo, C. Di Natale, G. Ferri, E. Martinelli, R. Paolesse, V. Stornelli, Low-voltage low-power integrated analog lock-in amplifier for gas sensor applications. Sensors Actuators B Chem. 144(2), 400–406 (2010)

    Article  Google Scholar 

  • A. De Marcellis, G. Ferri, P. Mantenuto, A. D’Amico, in A New Single-Chip Analog Lock-in Amplifier with Automatic Phase and Frequency Tuning for Physical/Chemical Noisy Phenomena Detection. 2013 5th IEEE International Workshop on Advances in Sensors and Interfaces (IWASI), (2013), pp. 121–124. IEEE

  • D.C. Duffy, J.C. Mcdonald, O.J.A. Schueller, G.M. Whitesides. Rapid prototyping of microfluidic systems in poly ( dimethylsiloxane ) Anal. Chem. 70(23), 4974–4984 (1998)

  • S. Emaminejad, K.H. Paik, V. Tabard-Cossa, M. Javanmard, Portable cytometry using microscale electronic sensing. Sensors and Actuators B: Chemical. 224, 275–281 (2016)

    Article  Google Scholar 

  • S. Emaminejad, S. Talebi, R.W. Davis, M. Javanmard, Multielectrode sensing for extraction of signal from noise in impedance cytometry. IEEE Sensors Journal 15(5), 2715–2716 (2015)

    Google Scholar 

  • FEMTO, Single board lock-in amplifier series LIA-BVD 150 H 19″ board (2017)

  • M. Gabal, N. Medrano, B. Calvo, P.A. Martínez, S. Celma, M.R. Valero, A complete low voltage analog lock-in amplifier to recover sensor signals buried in noise for embedded applications. Procedia Eng 5, 74–77 (2010)

    Article  Google Scholar 

  • A. Gnudi, L. Colalongo, G. Baccarani, Integrated lock-in amplifier for sensor applications. Solid-State Circuits Conference, 1999. ESSCIRC ‘99. Proceedings of the 25th European, pp. 58–61, (1999)

  • J. Gu, N. McFarlane, in A low power multi-frequency current mode lock-in amplifier for impedance sensing. 2015 IEEE International Instrumentation and Measurement Technology Conference (I2MTC), (2015), pp. 494–499. IEEE

  • L.A. Herzenberg, D. Parks, B. Sahaf, O. Perez, M. Roederer, The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford. Clin. Chem. 48(10), 1819–1827 (2002)

    Google Scholar 

  • H. Huang, S. Palermo, A TDC-based front-end for rapid impedance spectroscopy,” in Midwest Symposium on Circuits and Systems, 2013, pp. 169–172

  • T. Instruments, PCB design guidelines for reduced EMI. (1999)

    Google Scholar 

  • Z. Instruments, HF2IS impedance spectroscope (2017)

  • M. Javanmard, R.W. Davis, A microfluidic platform for electrical detection of DNA hybridization. Sensors and Actuators B: Chemical 154(1), 22–27 (2011)

    Article  Google Scholar 

  • J. Jiang, X. Wang, R. Chao, Y. Ren, C. Hu, Z. Xu, G. Logan, Sensors and actuators B : Chemical smartphone based portable bacteria pre-concentrating microfluidic sensor and impedance sensing system. Sensors Actuators B Chem. 193(2014), 653–659 (2016)

    Google Scholar 

  • P. Kassanos, I.F. Triantis, A. Demosthenous, A CMOS magnitude/phase measurement Chip for impedance spectroscopy. IEEE Sensors J. 13(6), 2229–2236 (2013)

    Article  Google Scholar 

  • P. Kassanos, L. Constantinou, I.F. Triantis, A. Demosthenous, An integrated analog readout for multi-frequency bioimpedance measurements. IEEE Sensors J. 14(8), 2792–2800 (2014)

    Article  Google Scholar 

  • K. H. Lee, J. Nam, S. Choi, H. Lim, S. Shin, G. H. Cho, A CMOS impedance cytometer for 3D flowing single-cell real-time analysis with ΔΣ error correction. in Digest of Technical Papers - IEEE International Solid-State Circuits Conference, vol. 55, 2012, pp. 304–305

  • J. Lichtenberg, N.F. de Rooij, E. Verpoorte, A microchip electrophoresis system with integrated in-plane electrodes for contactless conductivity detection. Electrophoresis 23(21), 3769–3780 (2002)

    Article  Google Scholar 

  • Z. Lin, X. Cao, P. Xie, M. Liu, M. Javanmard, PicoMolar level detection of protein biomarkers based on electronic sizing of bead aggregates: theoretical and experimental considerations. Biomed. Microdevices 17(6), 1–7 (2015)

    Google Scholar 

  • A. Manickam, C.A. Johnson, S. Kavusi, A. Hassibi, Interface design for CMOS-integrated electrochemical impedance spectroscopy (EIS) biosensors. Sensors (Basel) 12(11), 14467–14488 (2012)

    Article  Google Scholar 

  • U. Marschner, H. Grätz, B. Jettkant, D. Ruwisch, G. Woldt, W. Fischer, B. Clasbrummel, Physical Integration of a wireless lock-in measurement of hip prosthesis vibrations for loosening detection. Sensors Actuators A 156, 145–154 (2009)

    Article  Google Scholar 

  • P.M. Maya-Hernández, L.C. Álvarez-Simón, M.T. Sanz-Pascual, B. Calvo-López, An integrated low-power lockin amplifier and its application to gas detection. Sensors 14(9), 15880–15899 (2014)

    Article  Google Scholar 

  • J. Mok, M.N. Mindrinos, R.W. Davis, M. Javanmard, Digital microfluidic assay for protein detection. Proc. Natl. Acad. Sci. 111 (6):2110-2115 (2014)

  • P. Murali, I. Izyumin, D. Cohen, J. C. Chien, A. M. Niknejad, B. Boser, 24.6 A CMOS micro-flow cytometer for magnetic label detection and classification. in Digest of Technical Papers - IEEE International Solid-State Circuits Conference, vol. 57, 2014, pp. 422–423

  • A. Ozcan, Mobile phones democratize and cultivate next-generation imaging, diagnostics and measurement tools. Lab Chip 14, 3187–3194 (2014)

    Article  Google Scholar 

  • B. Sanou, ICT Facts & Figures. The world in 2015. ITU 150 AÑOS (1865–2015) (2015), [Online]. Available: http://www.itu.int/en/ITU-D/Statistics/Documents/facts/ICTFactsFigures2015.pdf

  • M.O. Sonnaillon, F.J. Bonetto, A low-cost, high-performance, digital signal processor-based lock-in amplifier capable of measuring multiple frequency sweeps simultaneously. Rev. Sci. Instrum. 76(2), 024703 (2005)

    Article  Google Scholar 

  • Stanford Research Systems. About Lock-In Amplifiers, Application Note #3, [online] Available: 1999,http://www.thinksrs.com/downloads/PDFs/ApplicationNotes/AboutLIAs.pdf. Accessed 15 May 2016

  • T. Sun, D. Holmes, S. Gawad, N. G. Green, H. Morgan, High speed multi-frequency impedance analysis of single particles in a microfluidic cytometer using maximum length sequences. 1034–1040 (2007)

  • A. Sun, T. Wambach, A.G. Venkatesh, D.A. Hall, in A low-cost smartphone-based electrochemical biosensor for point-of-care diagnostics. IEEE 2014 Biomedical Circuits and Systems Conference (BioCAS), (2014), pp. 312–315. IEEE

  • S.H. Tan, N.T. Nguyen, Y.C. Chua, T.G. Kang, Oxygen plasma treatment for reducing hydrophobicity of a sealed polydimethylsiloxane microchannel. Biomicrofluidics 4(3), 032204 (2010)

    Article  Google Scholar 

  • K. Townsend, C. Cufí, R. Davidson, Getting started with Bluetooth low energy: tools and techniques for lowpower networking (O'Reilly Media, Inc, California, 2014)

    Google Scholar 

  • T. Wilmshurst, Signal recovery from noise in electronic instrumentation, 2nd edn. (Taylor&Francis Group, New York, 1990)

    Book  Google Scholar 

  • Y. Xia, G.M. Whitesides, Soft lithography. no. 12, (1998)

  • C. Yang, D. Rairigh, A. Mason, Fully integrated impedance spectroscopy systems for biochemical sensor array. 2007 IEEE Biomedical Circuits and Systems Conference, pp. 21–24 (2007)

  • C. Yang, S.R. Jadhav, R.M. Worden, A.J. Mason, Compact low-power impedance-to-digital converter for sensor Array microsystems. IEEE J. Solid State Circuits 44(10), 2844–2855 (2009)

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Professor M. Caggiano from the Electrical and Computer Engineering Department, Rutgers University for useful discussions. This work was partially funded by the National Science Foundation Instrumentation Development for Biological Research Grant award number 1556263.

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Author notes

  1. Niloy Talukder and Abbas Furniturewalla contributed equally to this work.

Authors and Affiliations

  1. Department of Electrical and Computer Engineering, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA

    Niloy Talukder, Abbas Furniturewalla, Tuan Le, Matthew Chan, Shreyas Hirday, Xinnan Cao, Pengfei Xie, Zhongtian Lin, Azam Gholizadeh, Steve Orbine & Mehdi Javanmard

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  1. Niloy Talukder
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  2. Abbas Furniturewalla
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Correspondence to Mehdi Javanmard.

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Talukder, N., Furniturewalla, A., Le, T. et al. A portable battery powered microfluidic impedance cytometer with smartphone readout: towards personal health monitoring. Biomed Microdevices 19, 36 (2017). https://doi.org/10.1007/s10544-017-0161-8

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