Friday, June 9, 2023

Is Quantum Mechanics Necessary for Understanding Magnetic Resonance?

Is Quantum Mechanics Necessary for Understanding Magnetic Resonance? superimposed on Intermediate Physics for Medicine and Biology.
Hanson, L.,
Is Quantum Mechanics Necessary for
Understanding Magnetic Resonance?

Concepts Magn.Reson., 32:329–340, 2008
In Chapter 18 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss magnetic resonance imaging. Like many authors, we derive an expression for the magnetization of the tissue using quantum mechanics. Must we use quantum theory? In an article published in Concepts in Magnetic Resonance, Lars Hanson asks the same question: “Is Quantum Mechanics Necessary for Understanding Magnetic Resonance?” (Volume 32, Pages 329–340, 2008). The abstract is given below.
Educational material introducing magnetic resonance typically contains sections on the underlying principles. Unfortunately the explanations given are often unnecessarily complicated or even wrong. Magnetic resonance is often presented as a phenomenon that necessitates a quantum mechanical explanation whereas it really is a classical effect, i.e. a consequence of the common sense expressed in classical mechanics. This insight is not new, but there have been few attempts to challenge common misleading explanations, so authors and educators are inadvertently keeping myths alive. As a result, new students’ first encounters with magnetic resonance are often obscured by explanations that make the subject difficult to understand. Typical problems are addressed and alternative intuitive explanations are provided.
How would IPMB have to be changed to remove quantum mechanics from the analysis of MRI? Quantum ideas first appear in the last paragraph of Section 18.2 about the source of the magnetic moment, where we introduce the idea that the z-component of the nuclear spin in a magnetic field is quantized and can take on values that are integral multiples of the reduced Planck’s constant, ℏ. Delete that paragraph.

Section 18.3 is entirely based on quantum mechanics. To find the average value of the z-component of the spin, we sum over all quantum states, weighted by the Boltzmann factor. The end result is an expression for the magnetization as a function of the magnetic field. We could, alternatively, do this calculation classically. Below is a revised Section 18.3 that uses only classical mechanics and classical thermodynamics.
18.3 The Magnetization

The MR [magnetic resonance] image depends on the magnetization of the tissue. The magnetization of a sample, M, is the average magnetic moment per unit volume. In the absence of an external magnetic field to align the nuclear spins, the magnetization is zero. As an external magnetic field B is applied, the spins tend to align in spite of their thermal motion, and the magnetization increases, proportional at first to the external field. If the external field is strong enough, all of the nuclear magnetic moments are aligned, and the magnetization reaches its saturation value.

We can calculate how the magnetization depends on B. Consider a collection of spins of a nuclear species in an external magnetic field. This might be the hydrogen nuclei (protons) in a sample. The spins do not interact with each other but are in thermal equilibrium with the surroundings, which are at temperature T. We do not consider the mechanism by which they reach thermal equilibrium. Since the magnetization is the average magnetic moment per unit volume, it is the number of spins per unit volume, N, times the average magnetic moment of each spin: M=N<μ>, where μ is the magnetic moment of a single spin.

To obtain the average value of the z component of the magnetic moment, we must average over all spin directions, weighted by the probability that the z component of the magnetic moment is in that direction. Since the spins are in thermal equilibrium with the surroundings, the probability is proportional to the Boltzmann factor of Chap. 3, e–(U/kBT) = eμBcosθ/kBT, where kB is the Boltzmann constant. The denominator in Eq. 18.8 normalizes the probability:


The factor of sinθ arises when calculating the solid angle in spherical coordinates (see Appendix L). At room temperature μB/(kBT) ≪ 1 (see Problem 4), and it is possible to make the approximation ex ≈ 1 + x. The integral in the numerator then has two terms:
The first integral vanishes. The second is equal to 2/3 (hint: use the substitution u = cosθ). The denominator is

The first integral is 2; the second vanishes. Therefore we obtain
The z component of M is



which is proportional to the applied field.
The last place quantum mechanics is mentioned is in Section 18.6 about relaxation times. The second paragraph, starting “One way to analyze the effect…”, can be deleted with little loss of meaning; it is almost an aside.

So, to summarize, if you want to modify Chapter 18 of IPMB to eliminate any reference to quantum mechanics, then 1) delete the last paragraph of Section 18.2, 2) replace Section 18.3 with the modified text given above, and 3) delete the second paragraph in Section 18.6. Then, no quantum mechanics appears, and Planck’s constant is absent. Everything is classical, just the way I like it.

Friday, June 2, 2023

Calculus Made Easy

Intermediate Physics for Medicine and Biology assumes the reader knows calculus. Most medical doctors and biologists have studied some calculus, but I’m not sure they remember much of it. And most high school students, and even college freshman, have yet to take their first calculus course. What should these readers of IPMB do if they don’t know any calculus?  

Calculus Made Easy,
by Silvanus Thompson.
What these readers need is a quick and easy way to learn calculus without delving into all the subtle and complicated details. How can they do that? Read the delightful old book Calculus Made Easy, by Silvanus Thompson. Here’s the prologue:

Considering how many fools can calculate, it is surprising that it should be thought either a difficult or a tedious task for any other fool to learn how to master the same tricks. 
Some calculus-tricks are quite easy. Some are enormously difficult. The fools who write the textbooks of advanced mathematics — and they are mostly clever fools — seldom take the trouble to show you how easy the easy calculations are. On the contrary, they seem to desire to impress you with their tremendous cleverness by going about it in the most difficult way. 
Being myself a remarkably stupid fellow, I have had to unteach myself the difficulties, and now beg to present to my fellow fools the parts that are not hard. Master these thoroughly, and the rest will follow. What one fool can do, another can.
I know what you’re thinking: “That sounds like just what I need, but how much is it going to cost me?” The good news is that you can access the book for free online, at http://calculusmadeeasy.org.
Silvanus P. Thompson

The author, Silvanus Phillips Thompson (1851–1916), was an English physicist and a fellow of the Royal Society. I have a particular fondness for physicists from the Victorian era, especially one such as Thompson who was interested in science education and whose strength was his ability to explain difficult concepts clearly.

For those of you turned off by the dated style of Calculus Made Easy, written in 1910, I suggest Quick Calculus or Used Math instead. For those who, like me, love the Victorian style, I recommend Flatland by Edwin Abbott.

Enjoy!

Calculus Made Easy, by Silvanus P. Thompson, Part 1/2. A LibriVox audiobook. 

https://www.youtube.com/watch?v=hF2FLi5UnlE

 

Calculus Made Easy, by Silvanus P. Thompson, Part 2/2. A LibriVox audiobook.

https://www.youtube.com/watch?v=uqQtQNTKo-A

Friday, May 26, 2023

Terminal Speed of Microorganisms

A Paramecium aurelia seen through an optical microscope
A Paramecium aurelia seen through an optical microscope.
Source: Wikipedia (http://en.wikipedia.org/wiki/Image:Paramecium.jpg)

Homework Problem 28 at the end of Chapter 2 in Intermediate Physics for Medicine and Biology asks the reader to calculate the terminal speed of an animal falling in air. Although this problem provides insight, it includes a questionable assumption. Russ and I tell the student to “assume that the frictional force is proportional to the surface area of the animal.” If, however, the animal falls at low Reynolds number, this assumption is not valid. Instead, the drag force is given by Stokes’ law, which is proportional to the radius, not the surface area (radius squared). The new homework problem given below asks the reader to calculate the terminal speed for a microorganism falling through water at low Reynolds number.

Section 2.8

Problem 28 ½. Calculate the terminal speed, V, of a paramecium sinking in water. Assume that the organism is spherical with radius R, and that the Reynolds number is small so that the drag force is given by Stokes’ law. Include the effect of buoyancy. Let the paramecium’s radius be 100 microns and its specific gravity be 1.05. Verify that its Reynolds number is small.
The reader will first need to get the density ρ and viscosity η of water, which are ρ = 1000 kg/m3 and η = 0.001 kg/(m s). The specific gravity is not defined in IPMB, but it’s the density divided by the density of water, implying that the density of the paramecium is 1050 kg/m3. Finally, Stokes’ law is given in IPMB as Eq. 4.17, Fdrag = –6πRηV.

I’ll let you do your own calculation. I calculate the terminal speed to be about 1 mm/s, so it takes about a fifth of a second to sink one body diameter. The Reynolds number is 0.1, which is small, but not exceptionally small.

You should find that the terminal speed increases as the radius squared, in contrast to a drag force proportional to the surface area for which the terminal speed increases in proportion to the radius. Bigger organisms sink faster. The dependence of terminal speed on size is even more dramatic for aquatic microorganisms than for mammals falling in air. To paraphrase Haldane’s quip, “a bacterium is killed, a diatom is broken, a paramecium splashes,” except the speeds are small enough that none of the “wee little beasties” are really killed (the terminal speed is not terminal...get it?) and splashing is a high Reynolds number phenomenon.

Buoyancy is not negligible for aquatic animals. The effective density of a paramecium in air would be about 1000 kg/m3, but in water its effective density drops to a mere 50 kg/m3. Microorganisms are made mostly of water, so they are almost neutrally buoyant. In this homework problem, the effect of gravity is reduced to only five percent of what it would be if buoyancy were ignored.

A paramecium is a good enough swimmer that it can swim upward against gravity if it wants to. Its surface is covered with cilia that beat together like a Roman galley to produce the swimming motion (ramming speed!).

Whenever discussing terminal speed, one should remember that we assume the fluid is initially at rest. In fact, almost any volume of water will have currents moving at speeds greater than 1 mm/s, caused by tides, gravity, thermal convection, wind driven waves, or the wake of a fish swimming by. A paramecium would drift along with these currents. To observe the motion described in this new homework problem, one must be careful to avoid any bulk movement of water.

If you watched a paramecium sink in still water, would you notice any Brownian motion? You can calculate the root-mean-squared thermal speed with Eq. 4.12 in IPMB, using the mass of the paramecium as four micrograms and a temperature of 20° C. You get approximately 0.002 mm/s. That is less than 1% of the terminal speed, so you wouldn’t notice any random Brownian motion unless you measured extraordinarily carefully.

Friday, May 19, 2023

Breathless

Breathless: The Scientific Race to Defeat a Deadly Virus, by David Quammen, superimposed on Intermediate Physics for Medicine and Biology.
Breathless,
by David Quammen.
Whenever David Quammen has a new book, I put it on my “to read” list. Recently I finished his latest: Breathless: The Scientific Race to Defeat a Deadly Virus. Here’s the opening paragraph:
To some people it wasn’t surprising, the advent of this pandemic, merely shocking in the way a grim inevitability can shock. Those unsurprised people were infectious disease scientists. They had for decades seen such an event coming, like a small, dark dot on the horizon of western Nebraska, rumbling toward us at indeterminable speed and with indeterminable force, like a runaway chicken truck or an eighteen-wheeler loaded with rolled steel. The agent of the next catastrophe, they knew, would almost certainly be a virus. Not a bacterium as with bubonic plague, not some brain-eating fungus, not an elaborate protozoan of the sort that cause malaria. No, a virus—and, more specifically, it would be a “novel” virus, meaning not new to the world but newly recognized as infecting humans.
Quammen—a national treasure—is writing about covid (or, to use its official name, SARS-CoV-2). The coronavirus pandemic did not startle him; he almost predicted it in his earlier book Spillover. Quammen’s book Breathless is to tracing the origins and variants of covid as Walter Isaacson’s book The Code Breaker is to developing a vaccine for covid: required reading to understand what we’ve all been through the last three years. (And what I went through last month with my first case of covid, but I’m healthy now and feeling fine.)

Breathless describes the scientists who developed amazing software to analyze the virus’s genome, such as Áine O’Toole’s genomic pipeline PANGOLIN. Intermediate Physics for Medicine and Biology doesn’t discuss computational genomics, but at the heart of IPMB is the idea that you can combine a hard science like computer programming with a biological science like genomics to gain more information about, and insight into, biology and medicine. Quammen interviewed O’Toole about her experience writing the PANGOLIN program (“O’Toole stayed up late one night, and the next morning, there it was.”). But he didn’t interview just her. He talked to 96 heroic scientists and medical doctors who sought to understand covid, from those I’ve never heard of such as O’Toole to those we all are familiar with such as the brilliant Anthony Fauci. These interviews give the book credibility, especially given all the covid conspiracy theories and anti-vaccine nonsense that floats around the internet these days.

For anyone who may doubt the reality of evolution, I challenge you to try making sense of covid variants without it. Quammen takes us through the list: Alpha, Beta, Gamma, and the frightening Delta.
And after Delta, we knew, would come something else. The Greek alphabet contains twenty-four letters; at that point, the WHO [World Health Organization] list of variants only went up to mu. A virus will always and continually mutate, as I’ve noted, and the more individuals it infects, the more mutations it will produce. The more mutations, the more chances to improve its Darwinian success. Natural selection will act on it, eliminating waste, eliminating ineptitude, carving variation like a block of Carrara marble at the hands of Michelangelo, finding beautiful shapes, preserving the fittest. Evolution will happen. That’s not a variable, it’s a constant.
The latest variant, Omicron, seems to have appeared just as Quammen was finishing his book.
Omicron’s panoply of mutations reflects a period of active, extensive evolution—because the mutations not only occurred but they were preserved, within the lineage, suggesting they offered adaptive value.
One of the most interesting questions addressed in Breathless is the source of covid. Was it a lab accident, a spillover from an animal host (called a zoonotic event), or a malevolent attempt at biological warfare? Quammen doesn’t provide a definitive answer, but he favors the conclusions reached in a review article written by a group of prominent virologists led by Eddie Holmes.
Yes, Holmes and his coauthors agreed, the possibility of a lab accident can’t be entirely dismissed. Furthermore, that hypothesis may be nearly impossible to disprove. But it’s “highly unlikely,” they judged, “relative to the numerous and repeated human-animal contacts that occur routinely in the wildlife trade.” Failure to investigate that zoonotic dimension, with collaborative studies, crossing borders between countries and boundaries between species, would leave this pandemic festering and the world still very vulnerable to the next one.
Run, do not walk, to your library or bookstore and get Breathless. You need to read this book. Take special heed of Quammen’s alarming, disturbing, terrifying last sentence.
There are many more fearsome viruses where SARS-CoV-2 came from, wherever that was.

 A conversation with author and journalist David Quammen.

https://www.youtube.com/watch?v=jsREp6XI0nY

Friday, May 12, 2023

The Unscientific King: Charles III’s History Promoting Homeopathy

King Charles III of England was crowned this week. What’s that got to do with Intermediate Physics for Medicine and Biology? Well, the king is a big supporter of alternative medicine and one goal of IPMB is to highlight science-based medicine. If you believe in science, you don’t believe in alternative medicine. If science shows that some treatment works, it becomes part of medicine; there is nothing “alternative” about it. If science doesn’t show that some treatment works, then advocating for that treatment as “alternative medicine” is silly and foolish. In the realm of medicine, the king is a snake oil salesman.

Voodoo Science by Robert Park, superimposed on Intermediate Physics for Medicine and Biology.
Voodoo Science
by Robert Park.
Particularly worrisome is the king’s support for homeopathy. For those not familiar with homeopathic medicine, it works like this: a drug is repeatedly diluted, first by a 10:1 ratio of water to active ingredient (1X), then again a 10:1 dilution so the total dilution is by a factor of 100 (2X), then again a 10:1 dilution (3X), and so on. In Voodo Science, Bob Park described it this way:

The dilution limit is reached when a single molecule of the medicine remains. Beyond that point, there is nothing left to dilute. In over-the-counter homeopathic remedies, for example, a dilution of 30X is fairly standard. The notation 30X means the substance was diluted one part in ten and shaken, and then this was repeated sequentially thirty times. The final dilution would be one part medicine to 1,000,000,000,000,000,000,000,000,000,000 parts of water. That would be far beyond the dilution limit. To be precise, at a dilution of 30X you would have to drink 7,874 gallons of the solution to expect to get just one molecule of the medicine.

The supporters of homeopathy would have us believe that the water “remembers” the presence of the active ingredient.

King Charles’s support of alternative medicine was discussed in a recent article in The Scientist by Sophie Fessl, titled “The Unscientific King: Charles III’s History Promoting Homeopathy.” The first paragraph is reproduced below.

King Charles III has been conferred many new titles following the recent death of his mother, Queen Elizabeth II, but one existing title that remains is “Royal Patron of the Faculty of Homeopathy,” an organization of healthcare practitioners who also practice the pseudoscientific form of medicine. And the new king’s ties with alternative medicine go beyond this patronship and a dalliance with alternative medicine: In several instances, then-Prince Charles appears to have lobbied for homeopathy and other fields of alternative medicine. As King Charles ascends the throne, experts are reflecting on his influence on medical science in the UK as Prince of Wales, and how he might affect alternative medicine in the UK going forward as monarch. 

One book I have not read yet but is on my to-read list is Charles, The Alternative King, by Edzard Ernst, an advocate for evidence-based medicine and one of my heroes. In his preface, Ernst writes

This book chronicles Charles’s track record in promoting pseudo- and anti-science in the realm of alternative medicine. The new edition includes an additional final chapter with a summary of some of the scientific evidence that has emerged since this biography [originally titled Charles, The Alternative Prince] was first published. It demonstrates that the concerns about the safety and efficacy of the treatments in question are becoming even more disquieting. Whether such data will tame the alternative bee under the royal bonnet seems, however, doubtful.

This is the man who now sits on the thrown of England. We Americans owe George Washington so much.

Friday, May 5, 2023

Plans for a 6th Edition of Intermediate Physics for Medicine and Biology

Intermediate Physics for Medicine and Biology, 5th edition.
Thank you for your interest in the 5th edition of Intermediate Physics for Medicine and Biology. We’re considering a 6th edition and we would like to get your opinions and input. Some of you may have heard that about a year ago the senior author Russ Hobbie passed away. He was a joy to work with and will be missed. The 6th edition will have three authors: Hobbie, me, and a new coauthor Gene Surdutovich.

Gene and I would appreciate any feedback you have about our plans for the 6th edition. If you have time, please answer the questions below and email your responses to me at roth@oakland.edu. It would help us a lot to hear from you. I know that I listed many questions. Don’t worry if you have answers to only a few (or even just one). 

Thank you. 

  1. Was there any topic in the textbook that you think could be removed? 
  2. Was there any topic NOT in the textbook that you would like to see added in the 6th edition? 
  3. Regarding the homework problems, were they too easy? Too difficult? Too many? Too few? 
  4. How useful was the list of symbols at the end of each chapter? 
  5. Regarding the references, were there too many? Too few?
  6. Were the figures useful? Not useful? Easy to understand? Difficult to understand? 
  7. A few chapters had computer code. Was it useful? Was it unnecessary? 
  8. Are the Appendices useful? Unnecessary? Too many? Too few? 
  9. Do you have any general input or advice? 
  10. Do you have any specific issues with the 5th edition that you would like us to address?

Friday, April 28, 2023

Biomagnetism: The First Sixty Years

Roth, B. J., 2023, Biomagnetism: The first sixty years. Sensors, 23:4218.
Roth, B. J., 2023,
Biomagnetism: The first sixty years
.
Sensors
, 23:4218.
The last two blog posts have dealt with biomagnetism: the magnetic fields produced by our bodies. Some of you might have noticed hints about how these posts originated in “another publication.” That other publication is now published! This week, my review article “Biomagnetism: The First Sixty Years” appeared in the journal Sensors. The abstract is given below.
Biomagnetism is the measurement of the weak magnetic fields produced by nerves and muscle. The magnetic field of the heart—the magnetocardiogram (MCG)—is the largest biomagnetic signal generated by the body and was the first measured. Magnetic fields have been detected from isolated tissue, such as a peripheral nerve or cardiac muscle, and these studies have provided insights into the fundamental properties of biomagnetism. The magnetic field of the brain—the magnetoencephalogram (MEG)—has generated much interest and has potential clinical applications to epilepsy, migraine, and psychiatric disorders. The biomagnetic inverse problem, calculating the electrical sources inside the brain from magnetic field recordings made outside the head, is difficult, but several techniques have been introduced to solve it. Traditionally biomagnetic fields are recorded using superconducting quantum interference device (SQUID) magnetometers, but recently new sensors have been developed that allow magnetic measurements without the cryogenic technology required for SQUIDs.

The “First Sixty Years” refers to this year (2023) being six decades since the original biomagnetism publication in 1963, when Baule and McFee first measured the magnetocardiogram. 

My article completes a series of six reviews I’ve published in the last few years. 

Get the whole set! All are open access except the first. If you need a copy of that one, just email me at roth@oakland.edu and I’ll send you a pdf.

I’m not preparing any other reviews, so this will probably be the last one. But, you never know. 

You can learn more about biomagnetism in Chapter 8 of Intermediate Physics for Medicine and Biology.

Enjoy! 

A word cloud derived from "Biomagnetism: The First Sixty Years."


 

Friday, April 21, 2023

The Magnetic Field Associated with a Plane Wave Front Propagating Through Cardiac Tissue

When I was on the faculty at Vanderbilt University, my student Marcella Woods and I examined the magnetic field produced by electrical activity in a sheet of cardiac muscle. I really like this analysis, because it provides a different view of the mechanism producing the magnetic field compared to that used by other researchers studying the magnetocardiogram. In another publication, here is how I describe our research. I hope you find it useful.
Roth and Marcella Woods examined an action potential propagating through a two-dimensional sheet of cardiac muscle [58]. In Fig. 6, a wave front is propagating to the right, so the myocardium on the left is fully depolarized and on the right is at rest. Cardiac muscle is anisotropic, meaning it has a different electrical conductivity parallel to the myocardial fibers than perpendicular to them. In Fig. 6, the fibers are oriented at an angle to the direction of propagation. The intracellular voltage gradient is in the propagation direction (horizontal in Fig. 6), but the anisotropy rotates the intracellular current toward the fiber axis. The same thing happens to the extracellular current, except that in cardiac muscle the intracellular conductivity is more anisotropic than the extracellular conductivity, so the extracellular current is not rotated as far. Continuity requires that the components of the intra- and extracellular current densities in the propagation direction are equal and opposite. Their sum therefore points perpendicular to the direction of propagation, creating a magnetic field that comes out of the plane of the tissue on the left and into the plane on the right (Fig. 6) [58–60].
Figure 6. The current and magnetic field produced by a planar wave front propagating in a two-dimensional sheet of cardiac muscle. The muscle is anisotropic with a higher conductivity along the myocardial fibers.

This perspective of the current and magnetic field in cardiac muscle is unlike that ordinarily adopted when analyzing the magnetocardiogram, where the impressed current is typically taken as in the same direction as propagation. Nonetheless, experiments by Jenny Holzer in Wikswo’s lab confirmed the behavior shown in Fig. 6 [61].

The main references are:

58. Roth, B.J.; Woods, M.C. The magnetic field associated with a plane wave front propagating through cardiac tissue. IEEE Trans. Biomed. Eng. 1999, 46, 1288–1292.

61. Holzer, J.R.; Fong, L.E.; Sidorov, V.Y.; Wikswo, J.P.; Baudenbacher, F. High resolution magnetic images of planar wave fronts reveal bidomain properties of cardiac tissue. Biophys. J. 2004, 87, 4326–4332. 

You can learn more about how magnetic fields are generated by cardiac muscle by reading about what happens at the apex of the heart. Or, solve homework problem 19 in Chapter 8 of Intermediate Physics for Medicine and Biology.

Friday, April 14, 2023

The Magnetoencephalogram is Not Sensitive to a Radial Dipole

One of the key limitations of the magnetoencephalogram (MEG) is that it’s not sensitive to a radial dipole. What does this mean? The MEG is the magnetic field outside the head produced by the electrical activity of neurons in the brain. Often the source of this activity can be described by a current dipole, p, representing the intracellular current in the neurons. Because current flows in continuous loops, a dipole is surrounded by extracellular “return currents” flowing throughout the brain. Often the brain can be approximated as a sphere.

In Intermediate Physics for Medicine and Biology, Russ Hobbie and I explain the lack of a magnetic signal from a radial dipole this way:
One can see from the symmetry argument in the caption of Fig. 8.19 that in a spherically symmetric conducting medium the radial component of p and its return currents do not generate any magnetic field outside the sphere. Therefore the MEG is most sensitive to detecting activity in the fissures of the cortex, where the trunk of the postsynaptic dendrite is perpendicular to the surface of the fissure. A tangential component of p does produce a magnetic field outside a spherically symmetric conductor.

Figure 8.19 from IPMB is shown below.


While this text and figure do explain why a radial dipole has zero magnetic field, the explanation is a bit cryptic. Here is an alternative explanation that I wrote for another publication, and a better (or at least more colorful) figure.

A radial dipole produces no magnetic field (Fig. 8). This result is best proved using Ampere’s law: the magnetic field integrated along a closed loop is proportional to the net current threading the loop. The symmetry is sufficient that the integral over the path (dashed circle in Fig. 8) equals the path length times the magnetic field. The current produced by a dipole, including the return current, must be contained within the sphere because the region outside is not conducting. Hence, the net current threading the loop (the dipole plus the return current) is zero, so the magnetic field of a radial dipole vanishes.


Figure 8. The magnetic field of a radial dipole is zero outside a spherical conductor.

I hope this description is clearer!

Friday, April 7, 2023

I’ve Got Covid

For three years I’ve dodged the bullet, but no more; I have covid. I’m doing fine, thank you. For me the symptoms were similar to a moderate cold. My doctor put me on a five-day regimen of the antiviral drug Paxlovid plus some supplements to support my immune system (vitamin C, vitamin D3, and zinc). I’ve been isolating in our spare bedroom, which is boring but otherwise comfortable. I think I’m over the hump.

During the last few days I’ve taken several of those at-home covid rapid antigen tests. There’s some interesting physics at work in them. The figure below illustrates how they’re constructed. 

A covid rapid antigen test. From: Gupta et al. (2020) Nanotechnology-Based Approaches for the Detection of SARS-CoV-2. Frontiers in Nanotechnology, Volume 2, Article 589832.

To perform a test, you typically swab your nose, dip the swab in saline, stir, and then place a few drops of the solution onto the sample pad (A). You’re not detecting the virus itself, but instead the SARS-Cov 2 antibody. To explain what that means, I need to delve into a bit of immunology.

Our immune system produces a Y-shaped protein called an antibody, or immunoglobulin, that can selectively bind to an antigen, which is typically a protein that’s part of the coronavirus. The beauty of the antibody-antigen reaction is that it’s so specific: it lets the immune system attack a particular virus, bacteria, or other pathogen, ignoring everything else. When you get covid, your body launches an immune attack by producing SARS-Cov 2 antibodies. In the illustration above, the yellow Y is the antibody you are trying to detect. See David Goodsell’s marvelous painting of a virus being attacked by antibodies at the bottom of this post.

In the above figure, the conjugate pad (B) is where much of the physics lives. The pad contains gold nanoparticles (AuNP) that are coated with anti-human antibodies. An “anti-human antibody” is a molecule that binds selectively to a human antibody. In the figure, a red dot with a blue Y sticking out is a gold nanoparticle with an anti-human antibody bound to it.

A nitrocellulose membrane (NC membrane) is made from a mesh of nitrocellulose fibers (C). The mesh is porus and acts something like a wick, pulling the fluid from left to right by capillary action. This is why a device like that in the figure above is sometimes called a lateral flow test. The mesh also provides protected space for the nanoparticles and molecules to move around and interact in. The absorbent pad (D) acts like a sponge, soaking up the fluid as it reaches the right end of the detector, contributing to the capillary action and preventing any back flow.

As any SARS-Cov 2 antibody passes by a gold nanoparticle/anti-human antibody, it binds and the entire complex flows to the right together (in the figure, a combined red dot/blue Y/yellow Y).

Some additional molecules are bound to two spots on the nitrocellulose membrane. One, the test strip, has the SARS-cov 2 antigen. If any SARS-Cov 2 antibody passes by, it will bind to the antigen, immobilizing the gold nanoparticles. The other strip is goat anti-mouse antibody. How did a goat and mouse get involved? I don’t know. As I understand it, gold nanoparticles with antibodies that bind to the goat anti-mouse antibody are included in the conjugate pad, so regardless of if you have covid or not it serves as a control. If the nanoparticles don’t collect at the control strip, something is wrong.

Why bother with the gold nanoparticles? Their role is to transduce the signal so it becomes visible. Nanoparticles have interesting optical properties. When exposed to an electromagnetic field such as light, the electric field causes electrons to accumulate on one side of the particle creating a negative surface charge, leaving the opposite side positive from a lack of electrons. Such a distribution of charge oscillates at its own natural frequency (its plasma frequency), and when this frequency matches the driving frequency of the light there is a resonance. This “localized surface plasmon resonance” is effective at absorbing or scattering light. Scattering is particularly important because Rayleigh scattering (the scattering of light by particles with a radius much smaller than the wavelength of the light) depends on the sixth power of the particle radius. The binding of nanoparticles (which typically have a diameter of tens of nanometers) with large antibodies and antigens, and the aggregation of these complexes, can increase their effective size, accentuating scattering. In addition, the high concentration of the nanoparticles at the test and control strips enhance any optical effect. The end result is that you see a dark line if the nanoparticles are present.

So swab your nose, swish it in some saline, add a few drops to the sample pad, and wait. After about 15 minutes look at the results. If there is no control line, you’ve messed up. Throw the test away and try again. If there’s a control line but no test line, you’re negative. Be happy (but not too happy, because these tests are prone to false negatives). If there’s both a control line and a test line, you’ve got covid. The tests don’t give false positives too often, so you can be fairly confident you have the disease. Isolate yourself and talk to you doctor.

Where is the physics in all this? First, in the flow, which results from the surface tension created by the mesh of fibers, leading to capillary action. Second, in the optical properties of the nanoparticles, which provide the color that you see in the test and control strips. Unfortunately, Intermediate Physics for Medicine and Biology doesn’t discuss capillary action or surface plasmons, so you can’t learn about them there. Sorry; no book can cover everything. But there is interesting physics hidden in these tests.

Stay safe, dear reader, and may all your covid tests be negative.

This painting shows a cross section through a coronavirus surrounded by blood plasma, with neutralizing antibodies in bright yellow. The painting was commissioned for the cover of a special COVID-19 issue of Nature. From: David S. Goodsell, RCSB Protein Data Bank and Springer Nature; doi: 10.2210/rcsb_pdb/goodsell-gallery-025
 

A chemist explains how at-home covid tests work. From WIRED.

https://www.youtube.com/watch?v=2B-iZGNiPA0


See how a lateral flow immunoassay works.

https://www.youtube.com/watch?v=z07CK-4JoFo