Where’s My At-Home Molecular COVID Test?

Rapid PCR-quality results are possible, but cost and supply issues stand in the way of mass adoption

4 min read
A white device with a vial of colored fluid shows the words COVID-19, Positive and Negative. There is a green light next to Negative.

Lucira’s Check It COVID-19 molecular home test

Lucira

Free rapid antigen testing kits will soon begin arriving in mailboxes across the United States—and for many Americans, the at-home COVID-19 diagnostics could not come soon enough.

Demand for the self-tests has surged amidst the wave of infections and hospitalization fueled by the highly transmissible Omicron variant. And few people want to wait in long lines for PCR testing, which remains the most accurate means of detecting positive cases but requires processing in a centralized laboratory that can be slow to return results.

Mind you, there are more than those two testing options—although, judging by newsreports and healthinformationwebsites, you’d be hard-pressed to know that.

A third technology known as isothermal amplification is available that offers PCR-quality molecular results with the speed and convenience of at-home antigen testing. Three companies—Cue Health, Detect, and Lucira—now sell these types of COVID-19 testing kits direct to consumers

As Nathan Tanner, a senior scientist at New England Biolabs (NEB), explains: “You can take the test at home, wait 30 minutes, and have a level of confidence in your results that you would get from a PCR test.”

The only real downside, in his view, is the platform’s cost.

Although life-science reagents suppliers like NEB sell research-grade isothermal amplification kits for less than US $2 per test, the sticker price for consumer assays range from $50 to $75 a pop (with an additional one-time hardware cost of between $25 and $250 for some commercial products).

That per-test cost compares favorably with other molecular approaches such as PCR, which often sells for $100 or more, but is well above the $12 or so associated with most rapid-antigen assays, which pick up specific proteins (termed antigens) on the surface of viral particles. Up to eight of those cheaper—but less accurate—antigen tests are now insurance-reimbursable in the United States each month as well.

“People will pay a premium for molecular performance,” Tanner says.

The question is: How much are they willing to fork out?

Isothermal techniques work similarly to PCR, in which viral genetic material is copied over and over again until a detection threshold is reached. But isothermal approaches don’t require any preparation steps to purify samples.

What’s more, whereas PCR requires expensive equipment to heat and cool the sample dozens of times to reach a detection threshold, isothermal methods take advantage of special enzymes that can operate at just one temperature, usually around 65 °C.

A couple of double-A batteries—or even hand-warmer packets and an insulated thermos—are all it takes then to make the reactions run.

Results can then be read by eye using color-changing reagents or lateral-flow assays common to home-pregnancy tests, although companies that sell these types of COVID-19 testing kits generally incorporate some sort of printed circuit board that helps convert the signal into, say, a glowing light-emitting diode for ease of operability.

And it typically takes only about 20 to 30 minutes—or at most, an hour.

“It looks very easy, unintimidating, almost unimpressive,” says Erik Engelson, president and CEO of Lucira Health, maker of the Check It COVID-19 test (which uses a form of the technology known as loop-mediated isothermal amplification, or LAMP for short). “And the steps to using it are very simple: It’s just swab, stir, and click.”

“But,” Engelson adds, “what’s going on inside is incredibly sophisticated.”

In the view of John Schellenberg, a molecular microbiologist at the University of Manitoba, in Canada, isothermal testing provides the best of both worlds, offering PCR sensitivity with rapid-antigen usability, which could be especially useful in the face of Omicron.

The now-dominant variant tends to make people contagious much sooner after infection—and at lower viral loads—compared to previous forms of SARS-CoV-2, the coronavirus that causes COVID-19. That means reporting delays from PCR results, or the inability of antigen testing to pick up trace amounts of virus, could fuel unwanted disease spread.

“And so, a more sensitive and rapid test like LAMP would be much better, because it would be able to quickly capture small amounts of virus,” Schellenberg says.

The clientele for isothermal testing during the pandemic to date has mostly been businesses, sports leagues, and hospitals looking for PCR alternatives with a quicker turnaround time.

For example, the National Basketball Association and Major League Baseball both use Cue Health’s tests to regularly screen players, team staff members, and league officials. The U.S. government, Google, and the Mayo Clinic are all Cue patrons as well, as are many schools, prisons, and local health departments—which helps explain how annual revenue for the diagnostics company exceeded $600 million last year.

A phone sits on a surface in front of a white box device. A hand is pushing a long white swab into a smaller box in the device.Cue’s molecular COVID-19 test and appCue Health

“It’s used in many, many different scenarios by really discerning customers who care about performance,” says Ayub Khattak, cofounder, president, and CEO of Cue Health, which is also developing at-home molecular tests for influenza and other respiratory viruses.

Where it is not used as much is as a consumer substitute for rapid-antigen testing among people heading to family gatherings, attending church services, boarding flights, or going about other social activities that carry a risk of disease transmission. In those settings, rapid-antigen testing can provide a false sense of security, while PCR diagnostics are often inaccessible.

Isothermal testing offers “a no-compromise solution,” Khattak says.

“It would be nice if more people had access to it,” he adds.

Part of the problem is scalability. The technology is relatively new—developed for research purposes only around 20 years ago—and according to Engelson, “demand far exceeds manufacturing capacity.”

Lucira is aiming to produce 1 million tests per month by the middle of 2022. Across the United States, people currently run more than 3 million tests each day.

But price remains an obstacle, too. At-home molecular diagnostics will likely always cost more than antigen testing, Engelson says. “But as volumes come up, to the extent that we can make this more affordable, we absolutely will.”

At a certain price point, he and others predict that most people will gravitate to isothermal platforms.

“ ‘At-home test’ seems to be synonymous right now with rapid-antigen test,” notes Robert Meagher, a chemical engineer at Sandia National Laboratories, who has worked on LAMP-based diagnostics for mosquito-borne pathogens such as West Nile virus and Zika.

But should another variant emerge or a new pandemic strike, he expects that affordable isothermal test kits will become widespread and mainstream.

Could governments even one day be sending free isothermal test kits to households around the world? “I see that as quite possible,” Meagher says.

As Engelson bullishly proclaims: “Home testing of molecular quality is the future.”

The Conversation (1)
James Johnson27 Jan, 2022
LM

Mr. Dolgin,

Thanks for quite an interesting article. Could something similar to the Isothermal test could be generalized to detect any of a variety of pathogens and report the results back to a central health database or would pathogen specific reagents required to test for each.

There are so many pathogens, and forecast for even more possibly becoming pandemics in the future, until there is a need for ways to rapidly identify any pathogen even unknown ones (missing from DB) and inform health authorities so they can get an early start on containment.  With a smartphone app, information about where, when and who is infected with what could be collected and reported. 

Obtaining an accurate test of the specimen's RNA/DNA (possibly in addition to) reporting reaction products appears to be the difficult part. Interfacing with a smartphone for data collection and transmission to a central lab where further analysis could be performed possibly with the assistance of AI would seem straightforward.

I am told that a biomass spectrometer coupled with smartphone imaging may be capable of performing this in such a system. Is it possible for a system using Isothermal techniques to capture this information as well or, are specific reagents require for each pathogen?

Such a system would be of enormous value to the global community, that one would hope testing companies and smartphone manufacturers would team to create it. This would be much more useful than tracking software offered by Apple and Google. Your thoughts.

The Inner Beauty of Basic Electronics

Open Circuits showcases the surprising complexity of passive components

5 min read
Vertical
A photo of a high-stability film resistor with the letters "MIS" in yellow.
All photos by Eric Schlaepfer & Windell H. Oskay
Blue

Eric Schlaepfer was trying to fix a broken piece of test equipment when he came across the cause of the problem—a troubled tantalum capacitor. The component had somehow shorted out, and he wanted to know why. So he polished it down for a look inside. He never found the source of the short, but he and his collaborator, Windell H. Oskay, discovered something even better: a breathtaking hidden world inside electronics. What followed were hours and hours of polishing, cleaning, and photography that resulted in Open Circuits: The Inner Beauty of Electronic Components (No Starch Press, 2022), an excerpt of which follows. As the authors write, everything about these components is deliberately designed to meet specific technical needs, but that design leads to “accidental beauty: the emergent aesthetics of things you were never expected to see.”

From a book that spans the wide world of electronics, what we at IEEE Spectrum found surprisingly compelling were the insides of things we don’t spend much time thinking about, passive components. Transistors, LEDs, and other semiconductors may be where the action is, but the simple physics of resistors, capacitors, and inductors have their own sort of splendor.

High-Stability Film Resistor

A photo of a high-stability film resistor with the letters "MIS" in yellow.

All photos by Eric Schlaepfer & Windell H. Oskay

This high-stability film resistor, about 4 millimeters in diameter, is made in much the same way as its inexpensive carbon-film cousin, but with exacting precision. A ceramic rod is coated with a fine layer of resistive film (thin metal, metal oxide, or carbon) and then a perfectly uniform helical groove is machined into the film.

Instead of coating the resistor with an epoxy, it’s hermetically sealed in a lustrous little glass envelope. This makes the resistor more robust, ideal for specialized cases such as precision reference instrumentation, where long-term stability of the resistor is critical. The glass envelope provides better isolation against moisture and other environmental changes than standard coatings like epoxy.

15-Turn Trimmer Potentiometer

A photo of a blue chip
A photo of a blue chip on a circuit board.

It takes 15 rotations of an adjustment screw to move a 15-turn trimmer potentiometer from one end of its resistive range to the other. Circuits that need to be adjusted with fine resolution control use this type of trimmer pot instead of the single-turn variety.

The resistive element in this trimmer is a strip of cermet—a composite of ceramic and metal—silk-screened on a white ceramic substrate. Screen-printed metal links each end of the strip to the connecting wires. It’s a flattened, linear version of the horseshoe-shaped resistive element in single-turn trimmers.

Turning the adjustment screw moves a plastic slider along a track. The wiper is a spring finger, a spring-loaded metal contact, attached to the slider. It makes contact between a metal strip and the selected point on the strip of resistive film.

Ceramic Disc Capacitor

A cutaway of a Ceramic Disc Capacitor
A photo of a Ceramic Disc Capacitor

Capacitors are fundamental electronic components that store energy in the form of static electricity. They’re used in countless ways, including for bulk energy storage, to smooth out electronic signals, and as computer memory cells. The simplest capacitor consists of two parallel metal plates with a gap between them, but capacitors can take many forms so long as there are two conductive surfaces, called electrodes, separated by an insulator.

A ceramic disc capacitor is a low-cost capacitor that is frequently found in appliances and toys. Its insulator is a ceramic disc, and its two parallel plates are extremely thin metal coatings that are evaporated or sputtered onto the disc’s outer surfaces. Connecting wires are attached using solder, and the whole assembly is dipped into a porous coating material that dries hard and protects the capacitor from damage.

Film Capacitor

An image of a cut away of a capacitor
A photo of a green capacitor.

Film capacitors are frequently found in high-quality audio equipment, such as headphone amplifiers, record players, graphic equalizers, and radio tuners. Their key feature is that the dielectric material is a plastic film, such as polyester or polypropylene.

The metal electrodes of this film capacitor are vacuum-deposited on the surfaces of long strips of plastic film. After the leads are attached, the films are rolled up and dipped into an epoxy that binds the assembly together. Then the completed assembly is dipped in a tough outer coating and marked with its value.

Other types of film capacitors are made by stacking flat layers of metallized plastic film, rather than rolling up layers of film.

Dipped Tantalum Capacitor

A photo of a cutaway of a Dipped Tantalum Capacitor

At the core of this capacitor is a porous pellet of tantalum metal. The pellet is made from tantalum powder and sintered, or compressed at a high temperature, into a dense, spongelike solid.

Just like a kitchen sponge, the resulting pellet has a high surface area per unit volume. The pellet is then anodized, creating an insulating oxide layer with an equally high surface area. This process packs a lot of capacitance into a compact device, using spongelike geometry rather than the stacked or rolled layers that most other capacitors use.

The device’s positive terminal, or anode, is connected directly to the tantalum metal. The negative terminal, or cathode, is formed by a thin layer of conductive manganese dioxide coating the pellet.

Axial Inductor

An image of a cutaway of a Axial Inductor
A photo of a collection of cut wires

Inductors are fundamental electronic components that store energy in the form of a magnetic field. They’re used, for example, in some types of power supplies to convert between voltages by alternately storing and releasing energy. This energy-efficient design helps maximize the battery life of cellphones and other portable electronics.

Inductors typically consist of a coil of insulated wire wrapped around a core of magnetic material like iron or ferrite, a ceramic filled with iron oxide. Current flowing around the core produces a magnetic field that acts as a sort of flywheel for current, smoothing out changes in the current as it flows through the inductor.

This axial inductor has a number of turns of varnished copper wire wrapped around a ferrite form and soldered to copper leads on its two ends. It has several layers of protection: a clear varnish over the windings, a light-green coating around the solder joints, and a striking green outer coating to protect the whole component and provide a surface for the colorful stripes that indicate its inductance value.

Power Supply Transformer

A photo of a collection of cut wires
A photo of a yellow element on a circuit board.

This transformer has multiple sets of windings and is used in a power supply to create multiple output AC voltages from a single AC input such as a wall outlet.

The small wires nearer the center are “high impedance” turns of magnet wire. These windings carry a higher voltage but a lower current. They’re protected by several layers of tape, a copper-foil electrostatic shield, and more tape.

The outer “low impedance” windings are made with thicker insulated wire and fewer turns. They handle a lower voltage but a higher current.

All of the windings are wrapped around a black plastic bobbin. Two pieces of ferrite ceramic are bonded together to form the magnetic core at the heart of the transformer.

This article appears in the February 2023 print issue.

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