volume | PIER Journals

Abstract

For the last half a century, neurophysiology relies on patch clamp which neutralizes the ions to sense a signal. The smaller the patch, the efficiency is better. However, the limit has not been reached yet, and we accomplish it here. We add a spiral and a ring antenna to a coaxial probe to significantly reduce its self-resonance as the tip filters the ultra-low vibrations of protein's sub-molecular parts (10^-18 watts to 10^-22 watts) in a living cell environment with 10-6-watt noise. A probe tip added by a cavity resonator & a dielectric resonator acquires four distinct ultra-low noise signals simultaneously from a biomolecule, which is not possible using a patch clamp. Protein transmits ions and small molecules. Our probe estimates the ionic content of the molecule. Simultaneously it also measures the dipolar oscillations of its sub-molecular parts that regulates ionic interaction. We experimentally measure signals over a wide frequency domain. In that frequency domain, we map the mechanical, electrical, and magnetic vibrations of the element and record the relationship between its electric and ionic conductions. Dimension wise it is the ultimate resolution, consistent both in silico & in real experiments with the neuron cells --- the atomic pen instantly monitors a large number of dynamic molecular centers at a time.

1. Marsland, T. P. and E. Evans, "Dielectric measurements with an open-ended coaxial probe," IEEE Proceedings H — Microwaves, Antennas and Propagation, Vol. 134, 341-349, 1987.
doi:10.1049/ip-h-2.1987.0068

2. Meaney, P. M., B. B. Williams, S. D. Geimer, A. B. Flood, and H. M. Swartz, "A coaxial dielectric probe technique for distinguishing tooth enamel from dental resin," Adv. Biomed. Eng. Res., Vol. 3, 8-17, 2015.
doi:10.14355/aber.2015.03.002

3. Hagl, D. M., D. Popovic, S. C. Hagness, J. H. Booske, and M. Okoniewski, "Sensing volume of open-ended coaxial probes for dielectric characterization of breast tissue at microwave frequencies," IEEE Transactions on Microwave Theory and Techniques, Vol. 51, 1194-1206, 2003.
doi:10.1109/TMTT.2003.809626

4. Lazebnik, M., D. Popovic, L. McCartney, C. B. Watkins, M. J. Lindstrom, J. Harter, S. Sewall, T. Ogilvie, A. Magliocco, T. M. Breslin, W. Temple, D. Mew, J. H. Booske, M. Okoniewski, and S. C. Hagness, "A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries," Physics in Medicine and Biology, Vol. 52, 6093-6115, 2007.
doi:10.1088/0031-9155/52/20/002

5. Sheen, N. I. and I. M. Woodhead, "An open-ended coaxial probe for broad-band permittivity measurement of agricultural products," J. of Agricult. Eng. Res., Vol. 74, 193-202, 1999.
doi:10.1006/jaer.1999.0444

6. Grant, J. P., R. N. Clarke, G. T. Symm, and N. M. Spyrou, "A critical study of the open-ended coaxial line sensor technique for RF and microwave complex permittivity measurements," J. Phys. E Sci. Instrum., Vol. 22, 757-770, 1989.
doi:10.1088/0022-3735/22/9/015

7. Baudry, D., A. Louis, and B. Mazari, "Characterization of the open ended coaxial probe used for near-field measurements in EMC applications," Progress In Electromagnetics Research, Vol. 60, 311-333, 2006.
doi:10.2528/PIER05112501

8. Goodman, M. B. and S. R. Lockery, "Pressure polishing: a method for reshaping patch pipettes during fire polishing," J. Neurosci. Methods, Vol. 100, 13-15, 2000.
doi:10.1016/S0165-0270(00)00224-7

9. Novak, P., J. Gorelik, U. Vivekananda, A. I. Shevchuk, Y. S. Ermolyuk, R. J. Bailey, A. J. Bushby, G. W. J. Moss, D. A. Rusakov, D. Klenerman, D. M. Kullmann, K. E. Volynski, and Y. E. Korchev, "Nanoscale targeted Patch-clamp recordings of functional presynaptic ion channels," Neuron, Vol. 79, 1067-1077, 2013.
doi:10.1016/j.neuron.2013.07.012

10. Kodandaramaiah, S. B., G. T. Franzesi, B. Y. Chow, E. S. Boyden, and C. R. Forest, "Automated whole-cell patch-clamp electrophysiology of neurons in vivo," Nature Methods, Vol. 9, 585-587, 2012.
doi:10.1038/nmeth.1993

11. Zhao, Z., L. Luan, X. Wei, H. Zhu, X. Li, S. Lin, J. J. Siegel, R. A. Chitwood, and C. Xie, "Nanoelectronic coating enabled versatile multifunctional neural probes," Nano Lett., Vol. 17, 4588-4595, 2017.
doi:10.1021/acs.nanolett.7b00956

12. Gonzales, D. L., K. N. Badhiwala, D. G. Vercosa, B. W. Avants, Z. Liu, W. Zhong, and J. T. Robinson, "Scalable electrophysiology in intact small animals with nanoscale suspended electrode arrays," Nat. Nanotech., Vol. 12, 684-691, 2017.
doi:10.1038/nnano.2017.55

13. Schuhmann, T. G. J., J. Yao, G. Hong, T. M. Fu, and C. M. Lieber, "Syringe-injectable electronics with a plug-and-play input/output interface," Nano Lett., Vol. 17, 5836-5842, 2017.
doi:10.1021/acs.nanolett.7b03081

14. Azevedo, A. W. and R. I. Wilson, "Active mechanisms of vibration encoding and frequency filtering in central mechanosensory neurons," Neuron, Vol. 96, 1-15, 2017.
doi:10.1016/j.neuron.2017.09.004

15. Hudspeth, A. J. and R. S. Lewis, "A model for electrical resonance and frequency tuning in saccular hair cells of the bull-frog, Rana catesbeiana," J. Physiol., Vol. 400, 275-297, 1988.
doi:10.1113/jphysiol.1988.sp017120

16. Hutcheon, B. and Y. Yarom, "Resonance, oscillation and the intrinsic frequency preferences of neurons," Trends Neurosci., Vol. 23, 216-222, 2000.
doi:10.1016/S0166-2236(00)01547-2

17. Lundstrom, B. N., M. Famulare, L. B. Sorensen, W. J. Spain, and A. L. Fairhall, "Sensitivity of firing rate to input fluctuations depends on time scale separation between fast and slow variables in single neurons," J. Comput. Neurosci., Vol. 27, 277-290, 2009.
doi:10.1007/s10827-009-0142-x

18. Ratte, S., M. Lankarany, Y. A. Rho, A. Patterson, and S. A. Prescott, "Subthreshold membrane currents confer distinct tuning properties that enable neurons to encode the integral or derivative of their input," Front. Cell. Neurosci., Vol. 8, No. 452, 1-15, 2015.

19. Jin, L., Z. Han, J. Platisa, J. R. Wooltorton, L. B. Cohen, and V. A. Pieribone, "Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe," Neuron, Vol. 75, 779-785, 2012.
doi:10.1016/j.neuron.2012.06.040

20. Akemann, W., H. Mutoh, A. Perron, J. Rossier, and T. Knopfel, "Imaging brain electric signals with genetically targeted voltage-sensitive fluorescent proteins," Nat. Methods, Vol. 7, 643-649, 2010.
doi:10.1038/nmeth.1479

21. Maheswari, U., H. Tatsumi, Y. Katayama, and M. Ohtsua, "Observation of subcellular nanostructure of single neurons with an illumination mode photon scanning tunneling microscope," Optics Communications, Vol. 120, 325-334, 1995.
doi:10.1016/0030-4018(95)00462-H

22. Wang, Y., H. Fathali, D. Mishra, T. Olsson, J. D. Keighron, K. P. Skibicka, and A.-S. Cans, "Counting the number of glutamate molecules in single synaptic vesicles," J. Am. Chem. Soc., Vol. 141, No. 44, 17507-17511, 2019.
doi:10.1021/jacs.9b09414

23. Alanen, E., T. Lahtinen, and J. Nuutinen, "Variational formulation of open-ended coaxial line in contact with layered biological medium," IEEE Trans. on Biomed. Eng., Vol. 45, 1241-1248, 1998.
doi:10.1109/10.720202

24. Meaney, P. M., A. Gregory, N. Epstein, and K. D. Paulsen, "Microwave open-ended coaxial dielectric probe: interpretation of the sensing volume revisited," BMC Med. Phys., Vol. 14, 1756-6649, 2014.

25. Liao, K., Y. Wu, C. Qian, and G. Du, "An accurate equivalent circuit method of open ended coaxial probe for measuring the permittivity of materials," Electrical Power Systems and Computer, LNEE, X. Wan (eds)., Springer, Berlin, Heidelberg, 2011.

26. Naughton, J. R., T. Connolly, J. A. Varela, J. Lundberg, M. J. Burns, T. C. Chiles, J. P. Christianson, and M. J. Naughton, "Shielded coaxial optrode arrays for neurophysiology," Front Neurosci., Vol. 10, 252, 2016.

27. Singh, P., et al., "A self-operating time crystal model of the human brain: Can we replace entire brain hardware with a 3D fractal architecture of clocks alone?," Information, Vol. 11, No. 5, 238, 2020.
doi:10.3390/info11050238

28. Bandyopadhyay, A., "Chapter 7-A complete, integrated time crystal model of a human brain," Nanobrain. The Making of an Artificial Brain from a Time Crystal, 372, Taylor & Francis Inc. Imprint CRC Press Inc., Publication City/Country Bosa Roca, United States, 2020.

29. Saxena, K., et al., "Fractal, scale free electromagnetic resonance of a single brain extracted microtubule nanowire, a single tubulin protein and a single neuron," Fractal Fract, Vol. 4, No. 2, 11, 2020.
doi:10.3390/fractalfract4020011

30. Ghosh, S. S. Sahu, L. Agrawal, T. Shiga, and A. Bandyopadhyay, "Inventing a coaxial atomic resolution patch clamp to study a single resonating protein complex and ultra-low power communication deep inside a living neuron cell," J. Int. Neurosci., Vol. 15, 403-433, 2016.
doi:10.1142/S0219635216500321

31. Agrawal, L., S. Sahu, S. Ghosh, T. Shiga, D. Fujita, and A. Bandyopadhyay, "Inventing atomic resolution scanning dielectric microscopy to see a single protein complex operation live at resonance in a neuron without touching or adulterating the cell," J. Int. Neurosci., Vol. 15, 435-462, 2016.
doi:10.1142/S0219635216500333

32. Sahu, S., S. Ghosh, D. Fujita, and A. Bandyopadhyay, "Live visualizations of single isolated tubulin protein self-assembly via tunneling current: effect of electromagnetic pumping during spontaneous growth of microtubule," Sci. Rep., Vol. 4, No. 7303, 1-9, 2014.

33. Sahu, S., S. Ghosh, K. Hirata, D. Fujita, and A. Bandyopadhyay, "Multi-level memory switching properties of a single brain microtubule," Appl. Phys. Lett., Vol. 102, No. 123701, 1-4, 2013.

34. Sahu, S., S. Ghosh, B. Ghosh, K. Aswani, K. Hirata, D. Fujita, and A. Bandyopadhyay, "Atomic water channel controlling remarkable properties of a single brain microtubule: Correlating single protein to its supramolecular assembly," Biosensors and Bioelectronics, Vol. 47, 141-148, 2013.
doi:10.1016/j.bios.2013.02.050

35. Dan, Ye., L. Jun, and T. Jau, "Jet propulsion by microwave air plasma in the atomosphere," AIP Advances, Vol. 10, 055002, 2020.

36. Jaun, Y., et al., "Prediction and experimental measurement of the electromagnetic thrust generated by a microwave thruster system," Chinese Physics B, Vol. 22, No. 5, 050301, 2013.
doi:10.1088/1674-1056/22/5/050301

37. Yaduvanshi, R. S. and H. Parthasarathy, Chapter 1 --- Rectangular DRA fundamental background-rectangular dielectric resonator antenna — theory and design, Springer, 2016.

38. Behagi, A. A., "Chapter 4: Resonant circuits and filters — RF and microwave circuit design: A design approch using (ADS), advanced design system," Techno Search, 2015.

Mr. Pushpendra Singh

Dr. Subrata Ghosh

Dr. Pathik Sahoo

Dr. Kanad Ray

Dr. Daisuke Fujita

Dr. Anirban Bandyopadhyay