John Wikswo

John Peter Wikswo, Jr. (born October 6, 1949) is a biological physicist at Vanderbilt University. He was born in Lynchburg, Virginia, United States.

John Wikswo
Born (1949-10-06) October 6, 1949
NationalityAmerican
Scientific career
FieldsBiological Physics
InstitutionsVanderbilt University

Wikswo is noted for his work on biomagnetism and cardiac electrophysiology.

Graduate school

In the 1970s, Wikswo was a graduate student at Stanford University, where he worked under physicist William M. Fairbank, studying magnetocardiography.

Biomagnetism

In 1977 he became an assistant professor in the Department of Physics and Astronomy at Vanderbilt University, where he set up a laboratory to study living state physics. In 1980, he made the first measurement of the magnetic field of an isolated nerve, by threading the a frog sciatic nerve through a wire-wound, ferrite-core toroid and detecting the induced current using a SQUID magnetometer. [1] At the same time, Wikswo and Ken Swinney calculated the magnetic field of a nerve axon. [2] This work was followed a few years later by the first detailed comparison of the measured and calculated magnetic field produced by a single nerve axon. [3]

In a related line of study, Wikswo collaborated with Vanderbilt Professor John Barach to analyze the information content of biomagnetic versus bioelectric signals. [4] [5] [6]

Cardiac electrophysiology

One of Wikswo's most important contributions to science is his work in cardiac electrophysiology. In 1987 he began collaborating with doctors at the Vanderbilt Medical School, including Dan Roden, to study electrical propagation in the dog heart. [7] These studies led to the discovery of the virtual cathode effect in cardiac tissue: during electrical stimulation, the action potential wave front originated farther from the electrode in the direction perpendicular to the myocardial fibers than in the direction parallel to them. [8]

In parallel with these experimental studies, Wikswo analyzed the virtual cathode effect theoretically using the bidomain model, a mathematical model of the electrical properties of cardiac tissue that takes into account the anisotropic properties of both the intracellular and extracellular spaces. He first used the bidomain model to interpret biomagnetic measurements from strands of cardiac tissue. [9] Wikswo realized that the property of unequal anisotropy ratios in cardiac tissue (the ratio of electrical conductivity in the directions parallel and perpendicular to the myocardial fibers is different in the intracellular and extracellular spaces) has important implications for the magnetic field associated with a propagating action potential wave front in the heart. With Nestor Sepulveda, Wikswo use the finite element method to calculate the distinctive fourfold symmetric magnetic field pattern produced by an outwardly propagating wave front. [10]

Unequal anisotropy ratios has even an even greater impact during electrical stimulation of the heart. Again using the finite element model, Wikswo, Roth and Sepulveda predicted the transmembrane potential distribution around a unipolar electrode passing current into a passive, two-dimensional sheet of cardiac tissue. [11] They found that the region of depolarization under a cathode extends farther in the direction perpendicular to the fibers than parallel to the fibers, a shape that Wikswo named the dog-bone. This prediction immediately explained the virtual cathode effect found experimentally in the dog heart; they were observing the dog-bone shaped virtual cathode. Later simulations using an active, time-dependent bidomain model confirmed this conclusion. [12]

The calculation of the transmembrane potential by a unipolar electrode resulted in another prediction: regions of hyperpolarization adjacent to the cathode in the direction parallel to the myocardial fibers. Reversal of the stimulus polarization provided a mechanism for anodal stimulation of cardiac tissue. In order to test this prediction experimentally, Wikswo mastered the technique of optical mapping using voltage sensitive dyes, allowing the measurement of transmembrane potential using optical methods. With Marc Lin, Wikswo made high resolution measurements of excitation following stimulation through a unipolar electrode in a rabbit heart, and confirmed four mechanisms of electrical stimulation—cathode make, cathode break, anode make, and anode break—that had been predicted by bidomain calculations. [13] (Cathode and anode refer to the polarity of the stimulus, and make and break indicate if the excitation occurred following the start or end of the stimulus pulse.) Later experiments using this technique led to the prediction of a new type of cardiac arrhythmia, which Wikswo named quatrefoil reentry. [14]

SQUID magnetometers

In the 1990s, Wikswo began developing high spatial resolution SQUID magnetometers for mapping the magnetic field, to use in both biomagnetic studies and in non-destructive testing. [15] [16] [17] As is characteristic of Wikswo's work, he simultaneously developed theoretical methods to image a two-dimensional current density distribution from magnetic field measurements. [18]

VIIBRE

In the first two decades of the 21st century, Wikswo's research has emphasized the development and application of micro- and nano-scale devices for instrumenting and controlling single cells. [19] In 2001 he founded the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) to foster and enhance interdisciplinary research in the biophysical sciences and bioengineering at Vanderbilt. Wikswo refocused his research on systems biology, building microfabricated devices for measuring cellular properties and developing mathematical models of cellular signaling. He has designed organ-on-a-chip devices containing small populations of cells to fill the gaps between cell cultures and animals models, for use in pharmacology and toxicology. This work led to a second R&D 100 Award for the MultiWell MicroFormulator, which delivers and removes cell culture media to each of the 96 wells of a microwell plate for toxicology research.

Other positions

He also serves on the scientific advisory boards of Hypres Inc. and CardioMag Imaging Inc.[20]

Brief curriculum vitae

Awards

Year Award
1980–1982 Alfred P. Sloan Research Fellow
1984 IR-100 Award for Neuromagnetic Current Probe
1990 Fellow, American Physical Society
1999 Fellow, American Institute for Medical and Biological Engineering
2001 Fellow, American Heart Association
2005 Fellow, Biomedical Engineering Society
2006 Fellow, Heart Rhythm Society
2008 Fellow, IEEE
2017 R&D 100 Award for the MultiWell MicroFormulator
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References

  1. Wikswo JP Jr; Barach JP; Freeman JA (1980). "Magnetic field of a nerve impulse: First measurements". Science. 208 (4439): 53–55. Bibcode:1980Sci...208...53W. doi:10.1126/science.7361105. PMID 7361105.
  2. Swinney KR, Wikswo JP Jr (1980). "A calculation of the magnetic field of a nerve action potential". Biophysical Journal. 32 (2): 719–732. Bibcode:1980BpJ....32..719S. doi:10.1016/S0006-3495(80)85012-0. PMC 1327234. PMID 7260298.
  3. Roth BJ, Wikswo JP Jr (1985). "The magnetic field of a single axon: A comparison of theory and experiment". Biophysical Journal. 48 (1): 93–109. Bibcode:1985BpJ....48...93R. doi:10.1016/S0006-3495(85)83763-2. PMC 1329380. PMID 4016213.
  4. Wikswo JP Jr; Barach JP (1982). "Possible sources of new information in the magnetocardiogram". Journal of Theoretical Biology. 95 (4): 721–729. doi:10.1016/0022-5193(82)90350-2. PMID 7109652.
  5. Roth BJ, Wikswo JP Jr (1986). "Electrically-silent magnetic fields". Biophysical Journal. 50 (4): 739–745. Bibcode:1986BpJ....50..739R. doi:10.1016/S0006-3495(86)83513-5. PMC 1329851. PMID 3779008.
  6. Roth BJ, Guo WQ, Wikswo JP Jr (1988). "The effects of spiral anisotropy on the electric potential and the magnetic field at the apex of the heart". Mathematical Biosciences. 88 (2): 191–221. doi:10.1016/0025-5564(88)90042-9.
  7. Bajaj AK, Kopelman HA, ((Wikswo JP Jr)), Cassidy F, Woosley RL, Roden DM (1987). "Frequency- and orientation-dependent effects of mexiletine and quinidine on conduction in the intact dog heart". Circulation. 75 (5): 1065–1073. doi:10.1161/01.cir.75.5.1065. PMID 2436827.CS1 maint: multiple names: authors list (link)
  8. Wikswo JP Jr; Altemeier W; Balser JR; Kopelman HA; Wisialowski T; Roden DM (1991). "Virtual cathode effects during stimulation of cardiac muscle: Two-dimensional in vivo measurements". Circulation Research. 68 (2): 513–530. doi:10.1161/01.res.68.2.513. PMID 1991354.
  9. Roth BJ, Wikswo JP Jr (1986). "A bi-domain model for the extracellular potential and magnetic field of cardiac tissue". IEEE Transactions on Biomedical Engineering. 33 (4): 467–469. doi:10.1109/TBME.1986.325804. PMID 3957401.
  10. Sepulveda NG, Wikswo JP Jr (1987). "Electric and magnetic fields from two-dimensional anisotropic bisyncytia". Biophysical Journal. 51 (4): 557–568. Bibcode:1987BpJ....51..557S. doi:10.1016/S0006-3495(87)83381-7. PMC 1329928. PMID 3580484.
  11. Sepulveda NG, Roth BJ, Wikswo JP Jr (1989). "Current injection into a two-dimensional anisotropic bidomain". Biophysical Journal. 55 (5): 987–999. Bibcode:1989BpJ....55..987S. doi:10.1016/S0006-3495(89)82897-8. PMC 1330535. PMID 2720084.
  12. Roth BJ, Wikswo JP Jr (1994). "Electrical stimulation of cardiac tissue: A bidomain model with active membrane properties". IEEE Transactions on Biomedical Engineering. 41 (3): 232–240. doi:10.1109/10.284941. PMID 8045575.
  13. Wikswo JP Jr; Lin S-F; Abbas RA (1995). "Virtual electrodes in cardiac tissue: A common mechanism for anodal and cathodal stimulation". Biophysical Journal. 69 (6): 2195–2210. Bibcode:1995BpJ....69.2195W. doi:10.1016/S0006-3495(95)80115-3. PMC 1236459. PMID 8599628.
  14. Lin SF, Roth BJ, Wikswo JP Jr (1999). "Quatrefoil reentry in myocardium: An optical imaging study of the induction mechanism". Journal of Cardiovascular Electrophysiology. 10 (4): 574–586. doi:10.1111/j.1540-8167.1999.tb00715.x. PMID 10355700.
  15. Staton DJ, Ma YP, Sepulveda NG, Wikswo JP (1991). "High-resolution magnetic mapping using a SQUID magnetometer array". IEEE Transactions on Magnetics. 27 (2): 3237–3240. Bibcode:1991ITM....27.3237S. doi:10.1109/20.133901.
  16. Wikswo JP Jr (1995). "SQUID magnetometers for biomagnetism and non-destructive testing: Important questions and initial answers". IEEE Transactions on Applied Superconductivity. 5 (2): 74–120. Bibcode:1995ITAS....5...74W. doi:10.1109/77.402511.
  17. Jenks WG, Sadeghi SS, Wikswo JP Jr (1997). "SQUIDs for non-destructive evaluation". Journal of Physics D: Applied Physics. 30 (3): 293–323. Bibcode:1997JPhD...30..293J. doi:10.1088/0022-3727/30/3/002.
  18. Roth BJ, Sepulveda NG, Wikswo JP Jr (1989). "Using a magnetometer to image a two-dimensional current distribution". Journal of Applied Physics. 65 (1): 361–372. Bibcode:1989JAP....65..361R. doi:10.1063/1.342549.
  19. Walker GM, Sai JG, Richmond A, Chung CY, Stremler MA, Wikswo JP (2005). "Effects of flow and diffusion on chemotaxis studies in a microfabricated gradient generator". Lab on a Chip. 5 (6): 611–618. doi:10.1039/b417245k. PMC 2665276. PMID 15915253.
  20. "Executive Profile: John P. Wikswo Ph.D.", Bloomberg Businessweek, accessed 2014-01-21.

Further reading

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