Quantum Seeing without Looking? More Weirdness from the Quantum Realm

Quantum sensors have amazing powers.  They can detect the presence of an obstacle without ever interacting with it.  For instance, consider a bomb that is coated with a light sensitive layer that sets off the bomb if it absorbs just a single photon.  Then put this bomb inside a quantum sensor system and shoot photons at it.  Remarkably, using the weirdness of quantum mechanics, it is possible to design the system in such a way that you can detect the presence of the bomb using photons without ever setting it off.  How can photons see the bomb without illuminating it?  The answer is a bizarre side effect of quantum physics in which quantum wavefunctions are recognized as the root of reality as opposed to the pesky wavefunction collapse at the moment of measurement.

The ability for a quantum system to see an object with light, without exposing it, is uniquely a quantum phenomenon that has no classical analog.

All Paths Lead to Feynman

When Richard Feynman was working on his PhD under John Archibald Wheeler at Princeton in the early 1940’s he came across an obscure paper written by Paul Dirac in 1933 that connected quantum physics with classical Lagrangian physics.  Dirac had recognized that the phase of a quantum wavefunction was analogous to the classical quantity called the “Action” that arises from Lagrangian physics.  Building on this concept, Feynman constructed a new interpretation of quantum physics, known as the “many histories” interpretation, that occupies the middle ground between Schrödinger’s wave mechanics and Heisenberg’s matrix mechanics.  One of the striking consequences of the many histories approach is the emergence of the principle of least action—a classical concept—into interpretations of quantum phenomena.  In this approach, Feynman considered ALL possible histories for the propagation of a quantum particle from one point to another, he tabulated the quantum action in the phase factor, and he then summed all of these histories.

One of the simplest consequences of the sum over histories is a quantum interpretation of Snell’s law of refraction in optics.  When summing over all possible trajectories of a photon from a point above to a point below an interface, there are a subset of paths for which the action integral varies very little from one path in the subset to another.  The consequence of this is that the phases of all these paths add constructively, producing a large amplitude to the quantum wavefunction along the centroid of these trajectories.  Conversely, for paths far away from this subset, the action integral takes on many values and the phases tend to interfere destructively, canceling the wavefunction along these other paths.  Therefore, the most likely path of the photon between the two points is the path of maximum constructive interference and hence the path of stationary action.  It is simple so show that this path is none other than the classical path determined by Snell’s Law and equivalently by Fermat’s principle of least time.  With the many histories approach, we can add the principle of least (or stationary) action to the list of explanations of Snell’s Law.  This argument holds as well for an electron (with mass and a de Broglie wavelength) as it does for a photon, so this not just a coincidence specific to optics but is a fundamental part of quantum physics.

A more subtle consequence of the sum over histories view of quantum phenomena is Young’s double slit experiment for electrons, shown at the top of Fig 1.  The experiment consists of a source that emits only a single electron at a time that passes through a double-slit mask to impinge on an electron detection screen.  The wavefunction for a single electron extends continuously throughout the full spatial extent of the apparatus, passing through both slits.  When the two paths intersect at the screen, the difference in the quantum phases of the two paths causes the combined wavefunction to have regions of total constructive interference and other regions of total destructive interference.  The probability of detecting an electron is proportional to the squared amplitude of the wavefunction, producing a pattern of bright stripes separated by darkness.  At positions of destructive interference, no electrons are detected when both slits are open.  However, if an opaque plate blocks the upper slit, then the interference pattern disappears, and electrons can be detected at those previously dark locations.  Therefore, the presence of the object can be deduced by the detection of electrons at locations that should be dark.

Fig. 1  Demonstration of the sum over histories in a double-slit experiment for electrons. In the upper frame, the electron interference pattern on the phosphorescent screen produces bright and dark stripes.  No electrons hit the screen in a dark stripe.  When the upper slit is blocked (bottom frame), the interference pattern disappears, and an electron can arrive at the location that had previously been dark.

Consider now when the opaque plate is an electron-sensitive detector.  In this case, a single electron emitted by the source can be detected at the screen or at the plate.  If it is detected at the screen, it can appear at the location of a dark fringe, heralding the presence of the opaque plate.  Yet the quantum conundrum is that when the electron arrives at a dark fringe, it must be detected there as a whole, it cannot be detected at the electron-sensitive plate too.  So how does the electron sense the presence of the detector without exposing it, without setting it off? 

In Feynman’s view, the electron does set off the detector as one possible history.  And that history interferes with the other possible history when the electron arrives at the screen.  While that interpretation may seem weird, mathematically it is a simple statement that the plate blocks the wavefunction from passing through the upper slit, so the wavefunction in front of the screen, resulting from all possible paths, has no interference fringes (other than possible diffraction from the lower slit).  From this point of view, the wavefunction samples all of space, including the opaque plate, and the eventual absorption of a photon one place or another has no effect on the wavefunction.  In this sense, it is the wavefunction, prior to any detection event, that samples reality.  If the single electron happens to show up at a dark fringe at the screen, the plate, through its effects on the total wavefunction, has been detected without interacting with the photon. 

This phenomenon is known as an interaction-free measurement, but there are definitely some semantics issues here.  Just because the plate doesn’t absorb a photon, it doesn’t mean that the plate plays no role.  The plate certainly blocks the wavefunction from passing through the upper slit.  This might be called an “interaction”, but that phrase it better reserved for when the photon is actually absorbed, while the role of the plate in shaping the wavefunction is better described as one of the possible histories.

Quantum Seeing in the Dark

Although Feynman was thinking hard (and clearly) about these issues as he presented his famous lectures in physics at Cal Tech during 1961 to 1963, the specific possibility of interaction-free measurement dates more recently to 1993 when Avshalom C. Elitzur and Lev Vaidman at Tel Aviv University suggested a simple Michelson interferometer configuration that could detect an object half of the time without interacting with it [1].  They are the ones who first pressed this point home by thinking of a light-sensitive bomb.  There is no mistaking when a bomb goes off, so it tends to give an exaggerated demonstration of the interaction-free measurement. 

The Michelson interferometer for interaction-free measurement is shown in Fig. 2.  This configuration uses a half-silvered beamsplitter to split the possible photon paths.  When photons hit the beamsplitter, they either continue traveling to the right, or are deflected upwards.  After reflecting off the mirrors, the photons again encounter the beamsplitter, where, in each case, they continue undeflected or are reflected.  The result is that two paths combine at the beamsplitter to travel to the detector, while two other paths combine to travel back along the direction of the incident beam. 

Fig. 2 A quantum-seeing in the dark (QSD) detector with a photo-sensitive bomb. A single photon is sent into the interferometer at a time. If the bomb is NOT present, destructive interference at the detector guarantees that the photon is not detected. However, if the bomb IS present, it destroys the destructive interference and the photon can arrive at the detector. That photon heralds the presence of the bomb without setting it off. (Reprinted from Mind @ Light Speed)

The paths of the light beams can be adjusted so that the beams that combine to travel to the detector experience perfect destructive interference.  In this situation, the detector never detects light, and all the light returns back along the direction of the incident beam.  Quantum mechanically, when only a single photon is present in the interferometer at a time, we would say that the quantum wavefunction of the photon interferes destructively along the path to the detector, and constructively along the path opposite to the incident beam, and the detector would detect no photons.  It is clear that the unobstructed path of both beams results in the detector making no detections.

Now place the light sensitive bomb in the upper path.  Because this path is no longer available to the photon wavefunction, the destructive interference of the wavefunction along the detector path is removed.  Now when a single photon is sent into the interferometer, three possible things can happen.  One, the photon is reflected by the beamsplitter and detonates the bomb.  Two, the photon is transmitted by the beamsplitter, reflects off the right mirror, and is transmitted again by the beamsplitter to travel back down the incident path without being detected by the detector.  Three, the photon is transmitted by the beamsplitter, reflects off the right mirror, and is reflected off the beamsplitter to be detected by the detector. 

In this third case, the photon is detected AND the bomb does NOT go off, which succeeds at quantum seeing in the dark.  The odds are much better than for Young’s experiment.  If the bomb is present, it will detonate a maximum of 50% of the time.  The other 50%, you will either detect a photon (signifying the presence of the bomb), or else you will not detect a photon (giving an ambiguous answer and requiring you to perform the experiment again).  When you perform the experiment again, you again have a 50% chance of detonating the bomb, and a 25% chance of detecting it without it detonating, but again a 25% chance of not detecting it, and so forth.  All in all, every time you send in a photon, you have one chance in four of seeing the bomb without detonating it.  These are much better odds than for the Young’s apparatus where only exact detection of the photon at a forbidden location would signify the presence of the bomb.

It is possible to increase your odds above one chance in four by decreasing the reflectivity of the beamsplitter.  In practice, this is easy to do simply by depositing less and less aluminum on the surface of the glass plate.  When the reflectivity gets very low, let us say at the level of 1%, then most of the time the photon just travels back along the direction it came and you have an ambiguous result.  On the other hand, when the photon does not return, there is an equal probability of detonation as detection.  This means that, though you may send in many photons, your odds for eventually seeing the bomb without detonating it are nearly 50%, which is a factor of two better odds than for the half-silvered beamsplitter.  A version of this experiment was performed by Paul Kwiat in 1995 as a postdoc at Innsbruck with Anton Zeilinger.  It was Kwiat who coined the phrase “quantum seeing in the dark” as a catchier version of “interaction-free measurement” [2].

A 50% chance of detecting the bomb without setting it off sounds amazing, until you think that there is a 50% chance that it will go off and kill you.  Then those odds don’t look so good.  But optical phenomena never fail to surprise, and they never let you down.  A crucial set of missing elements in the simple Michelson experiment was polarization-control using polarizing beamsplitters and polarization rotators.  These are common elements in many optical systems, and when they are added to the Michelson quantum sensor, they can give almost a 100% chance of detecting the bomb without setting it off using the quantum Zeno effect.

The Quantum Zeno Effect

Photons carry polarization as their prime quantum number, with two possible orientations.  These can be defined in different ways, but the two possible polarizations are orthogonal to each other.  For instance, these polarization pairs can be vertical (V)  and horizontal (H), or they can be right circular  and left circular.  One of the principles of quantum state evolution is that a quantum wavefunction can be maintained in a specific state, even if it has a tendency naturally to drift out of that state, by repeatedly making a quantum measurement that seeks to measure deviations from that state.  In practice, the polarization of a photon can be maintained by repeatedly passing it through a polarizing beamsplitter with the polarization direction parallel to the original polarization of the photon.  If there is a deviation in the photon polarization direction by a small angle, then a detector on the side port of the polarizing beamsplitter will fire with a probability equal to the square of the sine of the deviation.  If the deviation angle is very small, say Δθ, then the probability of measuring the deviation is proportional to (Δθ)2, which is an even smaller number.  Furthermore, the probability that the photon will transmit through the polarizing beamsplitter is equal to 1-(Δθ)2 , which is nearly 100%.

This is what happens in Fig. 3 when the photo-sensitive bomb IS present. A single H-polarized photon is injected through a switchable mirror into the interferometer on the right. In the path of the photon is a polarization rotator that rotates the polarization by a small angle Δθ. There is nearly a 100% chance that the photon will transmit through the polarizing beamsplitter with perfect H-polarization reflect from the mirror and return through the polarizing beamsplitter, again with perfect H-polarization to pass through the polarization rotator to the switchable mirror where it reflects, gains another increment to its polarization angle, which is still small, and transmits through the beamsplitter, etc. At each pass, the photon polarization is repeatedly “measured” to be horizontal. After a number of passes N = π/Δθ/2, the photon is switched out of the interferometer and is transmitted through the external polarizing beamsplitter where it is detected at the H-photon detector.

Now consider what happens when the bomb IS NOT present. This time, even though there is a high amplitude for the transmitted photon, there is that Δθ amplitude for reflection out the V port. This small V-amplitude, when it reflects from the mirror, recombines with the H-amplitude at the polarizing beamsplitter to produce a polarization that has the same tilted polarizaton that it started with, sending it back in the direction from which it came. (In this situation, the detector on the “dark” port of the internal beamsplitter never sees the photon because of destructive interference along this path.) The photon is then rotated once more by the polarization rotator, and the photon polarization is rotated again, etc.. Now, after a number of passes N = π/Δθ/2, the photon has acquired a V polarization and is switched out of the interferometer. At the external polarizing beamsplitter it is reflected out of the V-port where it is detected at the V-photon detector.

Fig. 3  Quantum Zeno effect for interaction-free measurement.  If the bomb is present, the H-photon detector detects the output photon without setting it off.  The switchable mirror ejects the photon after it makes π/Δθ/2 round trips in the polarizing interferometer.

The two end results of this thought experiment are absolutely distinct, giving a clear answer to the question whether the bomb is present or not. If the bomb IS present, the H-detector fires. If the bomb IS NOT present, then the V-detector fires. Through all of this, the chance to set off the bomb is almost zero. Therefore, this quantum Zeno interaction-free measurement detects the bomb with nearly 100% efficiency with almost no chance of setting it off. This is the amazing consequence of quantum physics. The wavefunction is affected by the presence of the bomb, altering the interference effects that allow the polarization to rotate. But the likelihood of a photon being detected by the bomb is very low.

On a side note: Although ultrafast switchable mirrors do exist, the experiment was much easier to perform by creating a helix in the optical path through the system so that there is only a finite number of bounces of the photon inside the cavity. See Ref. [2] for details.

In conclusion, the ability for a quantum system to see an object with light, without exposing it, is uniquely a quantum phenomenon that has no classical analog.  No E&M wave description can explain this effect.

Further Reading

I first wrote about quantum seeing the dark in my 2001 book on the future of optical physics and technology: Nolte, D. D. (2001). Mind at Light Speed : A new kind of intelligence. (New York, Free Press)

More on the story of Feynman and Wheeler and what they were trying to accomplish is told in Chapter 8 of Galileo Unbound on the physics and history of dynamics: Nolte, D. D. (2018). Galileo Unbound: A Path Across Life, the Universe and Everything (Oxford University Press).

Paul Kwiat introduced to the world to interaction-free measurements in 1995 in this illuminating Scientific American article: Kwiat, P., H. Weinfurter and A. Zeilinger (1996). “Quantum seeing in the dark – Quantum optics demonstrates the existence of interaction-free measurements: the detection of objects without light-or anything else-ever hitting them.” Scientific American 275(5): 72-78.


[1] Elitzur, A. C. and L. Vaidman (1993). “QUANTUM-MECHANICAL INTERACTION-FREE MEASUREMENTS.” Foundations of Physics 23(7): 987-997.

[2] Kwiat, P., H. Weinfurter, T. Herzog, A. Zeilinger and M. A. Kasevich (1995). “INTERACTION-FREE MEASUREMENT.” Physical Review Letters 74(24): 4763-4766.

Physics in the Age of Contagion. Part 3: Testing and Tracing COVID-19

In the midst of this COVID crisis (and the often botched governmental responses to it), there have been several success stories: Taiwan, South Korea, Australia and New Zealand stand out. What are the secrets to their success? First, is the willingness of the population to accept the seriousness of the pandemic and to act accordingly. Second, is a rapid and coherent (and competent) governmental response. Third, is biotechnology and the physics of ultra-sensitive biomolecule detection.

Antibody Testing

A virus consists a protein package called a capsid that surrounds polymers of coding RNA. Protein molecules on the capsid are specific to the virus and are the key to testing whether a person has been exposed to the virus. These specific molecules are called antigens, and the body produces antibodies — large biomolecules — that are rapidly evolved by the immune system and released into the blood system to recognize and bind to the antigen. The recognition and binding is highly specific (though not perfect) to the capsid proteins of the virus, so that other types of antibodies (produced to fend off other infections) tend not to bind to it. This specificity enables antibody testing.

In principle, all one needs to do is isolate the COVID-19 antigen, bind it to a surface, and run a sample of a patient’s serum (the part of the blood without the blood cells) over the same surface. If the patient has produced antibodies against the COVID-19, these antibodies will attach to the antigens stuck to the surface. After washing away the rest of the serum, what remains are anti-COVID antibodies attached to the antigens bound to the surface. The next step is to determine whether these antibodies have been bound to the surface or not.

Fig. 1 Schematic of an antibody macromolecule. The total height of the molecule is about 3 nanometers. The antigen binding sites are at the ends of the upper arms.

At this stage, there are many possible alternative technologies to detecting the bound antibodies (see section below on the physics of the BioCD for one approach). A conventional detection approach is known as ELISA (Enzyme-linked immunosorbant assay). To detect the bound antibody, a secondary antibody that binds to human antibodies is added to the test well. This secondary antibody contains either a fluorescent molecular tag or an enzyme that causes the color of the well to change (kind of like how a pregnancy test causes a piece of paper to change color). If the COVID antigen binds antibodies from the patient serum, then this second antibody will bind to the first and can be detected by fluorescence or by simple color change.

The technical challenges associated with antibody assays relate to false positives and false negatives. A false positive happens when the serum is too sticky and some antibodies NOT against COVID tend to stick to the surface of the test well. This is called non-specific binding. The secondary antibodies bind to these non-specifically-bound antibodies and a color change reports a detection, when in fact no COVID-specific antibodies were there. This is a false positive — the patient had not been exposed, but the test says they were.

On the other hand, a false negative occurs when the patient serum is possibly too dilute and even though anti-COVID antibodies are present, they don’t bind sufficiently to the test well to be detectable. This is a false negative — the patient had been exposed, but the test says they weren’t. Despite how mature antibody assay technology is, false positives and false negatives are very hard to eliminate. It is fairly common for false rates to be in the range of 5% to 10% even for high-quality immunoassays. The finite accuracy of the tests must be considered when doing community planning for testing and tracking. But the bottom line is that even 90% accuracy on the test can do a lot to stop the spread of the infection. This is because of the geometry of social networks and how important it is to find and isolate the super spreaders.

Social Networks

The web of any complex set of communities and their interconnections aren’t just random. Whether in interpersonal networks, or networks of cities and states and nations, it’s like the world-wide-web where the most popular webpages get the most links. This is the same phenomenon that makes the rich richer and the poor poorer. It produces a network with a few hubs that have a large fraction of the links. A network model that captures this network topology is known as the Barabasi-Albert model for scale-free networks [1]. A scale-free network tends to have one node that has the most links, then a couple of nodes that have a little fewer links, then several more with even fewer, and so on, until there are a vary large number of nodes with just a single link each.

When it comes to pandemics, this type of network topology is both a curse and a blessing. It is a curse, because if the popular node becomes infected it tends to infect a large fraction of the rest of the network because it is so linked in. But it is a blessing, because if that node can be identified and isolated from the rest of the network, then the chance of the pandemic sweeping across the whole network can be significantly reduced. This is where testing and contact tracing becomes so important. You have to know who is infected and who they are connected with. Only then can you isolate the central nodes of the network and make a dent in the pandemic spread.

An example of a Barabasi-Albert network is shown in Fig. 2 fhavingor 128 nodes. Some nodes have many links out (and in) the number of links connecting a node is called the node degree. There are several nodes of very high degree (a degree around 25 in this case) but also very many nodes that have only a single link. It’s the high-degree nodes that matter in a pandemic. If they get infected, then they infect almost the entire network. This scale-free network structure emphasizes the formation of central high-degree nodes. It tends to hold for many social networks, but also can stand for cities across a nation. A city like New York has links all over the country (by flights), while my little town of Lafayette IN might be modeled by a single link to Indianapolis. That same scaling structure is seen across many scales from interactions among nations to interactions among citizens in towns.

Fig. 2 A scale-free network with 128 nodes. A few nodes have high degree, but most nodes have a degree of one.

Isolating the Super Spreaders

In the network of nodes in Fig. 2, each node can be considered as a “compartment” in a multi-compartment SIR model (see my previous blog for the two-compartment SIR model of COVID-19). The infection of each node depends on the SIR dynamics of that node, plus the infections coming in from links other infected nodes. The equations of the dynamics for each node are

where Aab is the adjacency matrix where self-connection is allowed (infection dynamics within a node) and the sums go over all the nodes of the network. In this model, the population of each node is set equal to the degree ka of the node. The spread of the pandemic across the network depends on the links and where the infection begins, but the overall infection is similar to the simple SIR model for a given average network degree

However, if the pandemic starts, but then the highest-degree node (the super spreader) is isolated (by testing and contact tracing), then the saturation of the disease across the network can be decreased in a much greater proportion than simply given by the population of the isolated node. For instance, in the simulation in Fig. 3, a node of degree 20 is removed at 50 days. The fraction of the population that is isolated is only 10%, yet the saturation of the disease across the whole network is decreased by more than a factor of 2.

Fig. 3 Scale-free network of 128 nodes. Solid curve is infection dynamics of the full network. Dashed curve is the infection when the highest-degree node was isolated at 50 days.

In a more realistic model with many more nodes, and full testing to allow the infected nodes and their connections to be isolated, the disease can be virtually halted. This is what was achieved in Taiwan and South Korea. The question is why the United States, with its technologically powerful companies and all their capabilities, was so unprepared or unwilling to achieve the same thing.

Python Code: NetSIRSF.py

#!/usr/bin/env python3
# -*- coding: utf-8 -*-
Created on Sat May 11 08:56:41 2019
@author: nolte
D. D. Nolte, Introduction to Modern Dynamics: Chaos, Networks, Space and Time, 2nd ed. (Oxford,2019)

# https://www.python-course.eu/networkx.php
# https://networkx.github.io/documentation/stable/tutorial.html
# https://networkx.github.io/documentation/stable/reference/functions.html

import numpy as np
from scipy import integrate
from matplotlib import pyplot as plt
import networkx as nx
import time
from random import random

tstart = time.time()


betap = 0.014;
mu = 0.13;

print('beta = ',betap)
print('betap/mu = ',betap/mu)

N = 128      # 50

facoef = 2
k = 1
nodecouple = nx.barabasi_albert_graph(N, k, seed=None)

indhi = 0
deg = 0
for omloop in nodecouple.node:
    degtmp = nodecouple.degree(omloop)
    if degtmp > deg:
        deg = degtmp
        indhi = omloop
print('highest degree node = ',indhi)
print('highest degree = ',deg)

colors = [(random(), random(), random()) for _i in range(10)]
nx.draw_circular(nodecouple,node_size=75, node_color=colors)
# function: omegout, yout = coupleN(G)
def coupleN(G,tlim):

    # function: yd = flow_deriv(x_y)
    def flow_deriv(x_y,t0):
        N = np.int(x_y.size/2)
        yd = np.zeros(shape=(2*N,))
        ind = -1
        for omloop in G.node:
            ind = ind + 1
            temp1 = -mu*x_y[ind] + betap*x_y[ind]*x_y[N+ind]
            temp2 =  -betap*x_y[ind]*x_y[N+ind]
            linksz = G.node[omloop]['numlink']
            for cloop in range(linksz):
                cindex = G.node[omloop]['link'][cloop]
                indx = G.node[cindex]['index']
                g = G.node[omloop]['coupling'][cloop]
                temp1 = temp1 + g*betap*x_y[indx]*x_y[N+ind]
                temp2 = temp2 - g*betap*x_y[indx]*x_y[N+ind]
            yd[ind] = temp1
            yd[N+ind] = temp2
        return yd
    # end of function flow_deriv(x_y)
    x0 = x_y
    t = np.linspace(0,tlim,tlim)      # 600  300
    y = integrate.odeint(flow_deriv, x0, t)        
    return t,y
    # end of function: omegout, yout = coupleN(G)

lnk = np.zeros(shape = (N,), dtype=int)
ind = -1
for loop in nodecouple.node:
    ind = ind + 1
    nodecouple.node[loop]['index'] = ind
    nodecouple.node[loop]['link'] = list(nx.neighbors(nodecouple,loop))
    nodecouple.node[loop]['numlink'] = len(list(nx.neighbors(nodecouple,loop)))
    lnk[ind] = len(list(nx.neighbors(nodecouple,loop)))

gfac = 0.1

ind = -1
for nodeloop in nodecouple.node:
    ind = ind + 1
    nodecouple.node[nodeloop]['coupling'] = np.zeros(shape=(lnk[ind],))
    for linkloop in range (lnk[ind]):
        nodecouple.node[nodeloop]['coupling'][linkloop] = gfac*facoef
x_y = np.zeros(shape=(2*N,))   
for loop in nodecouple.node:
x_y[N-1 ]= 0.01
x_y[2*N-1] = x_y[2*N-1] - 0.01
N0 = np.sum(x_y[N:2*N]) - x_y[indhi] - x_y[N+indhi]
print('N0 = ',N0)
tlim0 = 600
t0,yout0 = coupleN(nodecouple,tlim0)                           # Here is the subfunction call for the flow

plt.gca().set_ylim(1e-3, 1)
for loop in range(N):
    lines1 = plt.plot(t0,yout0[:,loop])
    lines2 = plt.plot(t0,yout0[:,N+loop])
    lines3 = plt.plot(t0,N0-yout0[:,loop]-yout0[:,N+loop])

    plt.setp(lines1, linewidth=0.5)
    plt.setp(lines2, linewidth=0.5)
    plt.setp(lines3, linewidth=0.5)

Itot = np.sum(yout0[:,0:127],axis = 1) - yout0[:,indhi]
Stot = np.sum(yout0[:,128:255],axis = 1) - yout0[:,N+indhi]
Rtot = N0 - Itot - Stot

# Repeat but innoculate highest-degree node
x_y = np.zeros(shape=(2*N,))   
for loop in nodecouple.node:
x_y[N-1] = 0.01
x_y[2*N-1] = x_y[2*N-1] - 0.01
N0 = np.sum(x_y[N:2*N]) - x_y[indhi] - x_y[N+indhi]
tlim0 = 50
t0,yout0 = coupleN(nodecouple,tlim0)

# remove all edges from highest-degree node
ee = list(nodecouple.edges(indhi))

lnk = np.zeros(shape = (N,), dtype=int)
ind = -1
for loop in nodecouple.node:
    ind = ind + 1
    nodecouple.node[loop]['index'] = ind
    nodecouple.node[loop]['link'] = list(nx.neighbors(nodecouple,loop))
    nodecouple.node[loop]['numlink'] = len(list(nx.neighbors(nodecouple,loop)))
    lnk[ind] = len(list(nx.neighbors(nodecouple,loop)))

ind = -1
x_y = np.zeros(shape=(2*N,)) 
for nodeloop in nodecouple.node:
    ind = ind + 1
    nodecouple.node[nodeloop]['coupling'] = np.zeros(shape=(lnk[ind],))
    x_y[ind] = yout0[tlim0-1,nodeloop]
    x_y[N+ind] = yout0[tlim0-1,N+nodeloop]
    for linkloop in range (lnk[ind]):
        nodecouple.node[nodeloop]['coupling'][linkloop] = gfac*facoef

tlim1 = 500
t1,yout1 = coupleN(nodecouple,tlim1)

t = np.zeros(shape=(tlim0+tlim1,))
yout = np.zeros(shape=(tlim0+tlim1,2*N))
t[0:tlim0] = t0
t[tlim0:tlim1+tlim0] = tlim0+t1
yout[0:tlim0,:] = yout0
yout[tlim0:tlim1+tlim0,:] = yout1

plt.gca().set_ylim(1e-3, 1)
for loop in range(N):
    lines1 = plt.plot(t,yout[:,loop])
    lines2 = plt.plot(t,yout[:,N+loop])
    lines3 = plt.plot(t,N0-yout[:,loop]-yout[:,N+loop])

    plt.setp(lines1, linewidth=0.5)
    plt.setp(lines2, linewidth=0.5)
    plt.setp(lines3, linewidth=0.5)

Itot = np.sum(yout[:,0:127],axis = 1) - yout[:,indhi]
Stot = np.sum(yout[:,128:255],axis = 1) - yout[:,N+indhi]
Rtot = N0 - Itot - Stot
plt.ylabel('Fraction of Sub-Population')
plt.title('Network Dynamics for COVID-19')

elapsed_time = time.time() - tstart
print('elapsed time = ',format(elapsed_time,'.2f'),'secs')

Caveats and Disclaimers

No effort in the network model was made to fit actual disease statistics. In addition, the network in Figs. 2 and 3 only has 128 nodes, and each node was a “compartment” that had its own SIR dynamics. This is a coarse-graining approach that would need to be significantly improved to try to model an actual network of connections across communities and states. In addition, isolating the super spreader in this model would be like isolating a city rather than an individual, which is not realistic. The value of a heuristic model is to gain a physical intuition about scales and behaviors without being distracted by details of the model.

Postscript: Physics of the BioCD

Because antibody testing has become such a point of public discussion, it brings to mind a chapter of my own life that was closely related to this topic. About 20 years ago my research group invented and developed an antibody assay called the BioCD [2]. The “CD” stood for “compact disc”, and it was a spinning-disk format that used laser interferometry to perform fast and sensitive measurements of antibodies in blood. We launched a start-up company called QuadraSpec in 2004 to commercialize the technology for large-scale human disease screening.

A conventional compact disc consists of about a billion individual nulling interferometers impressed as pits into plastic. When the read-out laser beam straddles one of the billion pits, it experiences a condition of perfect destructive interferences — a zero. But when it was not shining on a pit it experiences high reflection — a one. So as the laser scans across the surface of the disc as it spins, a series of high and low reflections read off bits of information. Because the disc spins very fast, the data rate is very high, and a billion bits can be read in a matter of minutes.

The idea struck me in late 1999 just before getting on a plane to spend a weekend in New York City: What if each pit were like a test tube, so that instead of reading bits of ones and zeros it could read tiny amounts of protein? Then instead of a billion ones and zeros the disc could read a billion protein concentrations. But nulling interferometers are the least sensitive way to measure something sensitively because it operates at a local minimum in the response curve. The most sensitive way to do interferometry is in the condition of phase quadrature when the signal and reference waves are ninety-degrees out of phase and where the response curve is steepest, as in Fig. 4 . Therefore, the only thing you need to turn a compact disc from reading ones and zeros to proteins is to reduce the height of the pit by half. In practice we used raised ridges of gold instead of pits, but it worked in the same way and was extremely sensitive to the attachment of small amounts of protein.

Fig. 4 Principle of the BioCD antibody assay. Reprinted from Ref. [3]

This first generation BioCD was literally a work of art. It was composed of a radial array of gold strips deposited on a silicon wafer. We were approached in 2004 by an art installation called “Massive Change” that was curated by the Vancouver Art Museum. The art installation travelled to Toronto and then to the Museum of Contemporary Art in Chicago, where we went to see it. Our gold-and-silicon BioCD was on display in a section on art in technology.

The next-gen BioCDs were much simpler, consisting simply of oxide layers on silicon wafers, but they were much more versatile and more sensitive. An optical scan of a printed antibody spot on a BioCD is shown in Fig. 5 The protein height is only about 1 nanometer (the diameter of the spot is 100 microns). Interferometry can measure a change in the height of the spot (caused by binding antibodies from patient serum) by only about 10 picometers averaged over the size of the spot. This exquisite sensitivity enabled us to detect tiny fractions of blood-born antigens and antibodies at the level of only a nanogram per milliliter.

Fig. 5 Interferometric measurement of a printed antibody spot on a BioCD. The spot height is about 1 nanomater and the diameter is about 100 microns. Interferometry can measure a change of height by about 10 picometers averaged over the spot.

The real estate on a 100 mm diameter disc was sufficient to do 100,000 antibody assays, which would be 256 protein targets across 512 patients on a single BioCD that would take only a few hours to finish reading!

Fig. 6 A single BioCD has the potential to measure hundreds of proteins or antibodies per patient with hundreds of patients per disc.

The potential of the BioCD for massively multiplexed protein measurements made it possible to imagine testing a single patient for hundreds of diseases in a matter of hours using only a few drops of blood. Furthermore, by being simple and cheap, the test would allow people to track their health over time to look for emerging health trends.

If this sounds familiar to you, you’re right. That’s exactly what the notorious company Theranos was promising investors 10 years after we first proposed this idea. But here’s the difference: We learned that the tech did not scale. It cost us $10M to develop a BioCD that could test for just 4 diseases. And it would cost more than an additional $10M to get it to 8 diseases, because the antibody chemistry is not linear. Each new disease that you try to test creates a combinatorics problem of non-specific binding with all the other antibodies and antigens. To scale the test up to 100 diseases on the single platform using only a few drops of blood would have cost us more than $1B of R&D expenses — if it was possible at all. So we stopped development at our 4-plex product and sold the technology to a veterinary testing company that uses it today to test for diseases like heart worm and Lymes disease in blood samples from pet animals.

Five years after we walked away from massively multiplexed antibody tests, Theranos proposed the same thing and took in more than $700M in US investment, but ultimately produced nothing that worked. The saga of Theranos and its charismatic CEO Elizabeth Holmes has been the topic of books and documentaries and movies like “The Inventor: Out for Blood in Silicon Valley” and a rumored big screen movie starring Jennifer Lawrence as Holmes.

The bottom line is that antibody testing is a difficult business, and ramping up rapidly to meet the demands of testing and tracing COVID-19 is going to be challenging. The key is not to demand too much accuracy per test. False positives are bad for the individual, because it lets them go about without immunity and they might get sick, and false negatives are bad, because it locks them in when they could be going about. But if an inexpensive test of only 90% accuracy (a level of accuracy that has already been called “unreliable” in some news reports) can be brought out in massive scale so that virtually everyone can be tested, and tested repeatedly, then the benefit to society would be great. In the scaling networks that tend to characterize human interactions, all it takes is a few high-degree nodes to be isolated to make infection rates plummet.


[1] A. L. Barabasi and R. Albert, “Emergence of scaling in random networks,” Science, vol. 286, no. 5439, pp. 509-512, Oct 15 (1999)

[2] D. D. Nolte, “Review of centrifugal microfluidic and bio-optical disks,” Review Of Scientific Instruments, vol. 80, no. 10, p. 101101, Oct (2009)

[3] D. D. Nolte and F. E. Regnier, “Spinning-Disk Interferometry: The BioCD,” Optics and Photonics News, no. October 2004, pp. 48-53, (2004)