Some recent developments in biodefense and early pathogen detection

Biodefense is the protection of people, animals, and plants from biological threats. This can be done through vaccination, treatment, and detection.

Some of the emerging trends in biodefense include the development of new vaccines and therapeutics, the use of nanotechnology for detection and decontamination, and the use of synthetic biology for the development of novel countermeasures.

In order to explore this technology space, I did a very simple search in Mergeflow, just for “biodefense”. Obviously this will miss many things that are relevant to biodefense but don’t use the term explicitly. But it’s a start.

Here is a snapshot of the data I started with (click on the image below to see the data):

A 360° data snapshot on biodefense in Mergeflow, including venture investments, market estimates, patents, R&D publications, news, and other sources.
A 360° data snapshot on biodefense in Mergeflow, including venture investments, market estimates, patents, R&D publications, news, and other sources.

I build software for a living, not biodefense solutions. But it seems to me that the most useful biodefense solutions can do rapid detection and analysis, are as non-invasive as possible (non-invasive is easier and quicker), and as affordable and portable as possible (“biodefense on a phone”?).

I started by looking at companies, then at some recent R&D in biodefense.

Biodefense and pathogen detection companies

BioFlyte

BioFlyte makes portable mass spectrometers for aerosol detection. These aerosols include viruses, bacteria, spores, opioids, and other substances.

The latest addition to their product line is a system for indoor detection of coronavirus and other respiratory pathogens. The system has integrated PCR test capability.

BioFlyte's system for detecting coronavirus and related pathogens. Image from BioFlyte's website.
BioFlyte’s system for detecting coronavirus and related pathogens. Image from BioFlyte’s website.

In April 2022, BioFlyte raised $6.1M Series A from Cottonwood Technology Fund and Anzu Partners.

OmniVis

OmniVis makes handheld devices for rapid pathogen detection, and a cloud-based computing platform that enables epidemiological modeling.

For cholera and E. coli bacteria detection, they use a method called LAMP (loop-mediated isothermal amplification). Work on detecting other pathogens such as malaria, HIV and blood sepsis is in progress.

OmniVis iSpyDx handheld device for rapid pathogen detection. Image from OmniVis website.
OmniVis iSpyDx handheld device for rapid pathogen detection. Image from OmniVis website.

OmniVis has received funding via the SBIR program (Small Business Innovation Research, a US federally funded program; SBIR is one of the public research funding data sets analyzed by Mergeflow):

Internal Control Design for a Portable Cholera Pathogen Detector

More recently they are investigating RT-LAMP (RT = reverse transcription) for RNA virus detection. Here is a paper from April 2022:

PD-LAMP smartphone detection of SARS-CoV-2 on chip

Beyond COVID, RT-LAMP is being investigated for detecting pathogens causing dengue, hepatitis and other diseases.

BioFluidica

BioFluidica makes a liquid biopsy diagnostics platform. Liquid biopsy is a non-invasive procedure used to collect and analyze cells from the blood in order to detect the presence of a disease. This type of biopsy is less invasive than traditional biopsies, which involve surgically removing tissue samples.

In February 2022, BioFluidica raised $6M Series B2 (I could not find names of the investors). This is in addition to funding from the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) program.

With the new funding, BioFluidica aims to develop accurate, rapid, low-cost, at-home tests for COVID-19. This will be enabled by BioFluidica’s Liquid Scan platform. At the core of this platform is a patented microfluidic chip:

Fluid-tight flow system to isolate biomarkers from a liquid sample

Dual-depth thermoplastic microfluidic device and related systems and methods

Avsana Labs

Avsana Labs is a spin-out company from the University of Texas at Dallas. The company commercializes recent research that uses a method called nanobubble detection. The goal is to use the technology for diagnosing respiratory syncytial virus (RSV). In children under age 1, RSV is the leading cause of pneumonia and bronchiolitis.

According to Avsana Labs’ website, their new test will deliver results within 20 minutes, cost under $15, and have a test specificity comparable to RT-PCR.

Mammoth Biosciences

Mammoth Biosciences makes diagnostics, therapeutics and protein discovery based on CRISPR technology (Nobel laureate Jennifer Doudna is a co-founder).

Using CRISPR for diagnostics promises high accuracy, versatility, and simple deployment. “Versatility” means that it should be possible to very quickly develop diagnostics for new pathogens.

In January 2022, Mammoth Biosciences has received emergency use authorization from the FDA for their CRISPR-based COVID-19 test.

Agilent's BenchCel platform. It can run Mammoth Bioscience's COVID-19 test. Image from Mammoth Bioscience's website.
Agilent’s BenchCel platform. It can run Mammoth Bioscience’s COVID-19 test. Image from Mammoth Bioscience’s website.

In September 2021, Mammoth Biosciences announced $195M funding from Foresite Capital, Senator Investment Group, Sixth Street, Greenspring Associates, Mayfield, Decheng Capital, NFX and Plum Alley, Redmile Group, Foresite Capital, and Amazon.

Some recent R&D in biodefense

Analyzing wastewater

Analyzing wastewater can reveal a lot about the health status of a community. This includes levels of chemicals, drugs, and pathogens. Not surprisingly, the topic of wastewater monitoring has gained momentum over the past two years, as you can see in the volume of science publications in the screenshot below (click on the image to see it in full size):

Science publications on wastewater monitoring have increased over the recent two years. Screenshot from Mergeflow.
Science publications on wastewater monitoring have increased over the recent two years. Screenshot from Mergeflow.

The first publication listed in the screenshot above provides a very recent overview:

Invited Perspective: The Promise of Wastewater Monitoring for Infectious Disease Surveillance

And here is a more general overview of the topic:

Wastewater provides a planet-wide laboratory for the study of human health

New methods for detecting single molecules with smartphones

Biomarkers of diseases typically occur in very low concentrations. So, if you want to detect a disease, you need a device that works with very few instances of the molecule you want to detect. So far, such devices have been very expensive and only work in dedicated test centers.

But recent research by a group from the Ludwig-Maximilians-University in Munich aims to change this. They have developed a prototype of a low-cost imaging system that can detect single molecules of a pathogen.

Schematic of a low-cost single molecule detection imaging device. Image from Trofymchuck, Glembockyte et al's 2021 paper in Nature Communications.
Schematic of a low-cost single molecule detection imaging device. Image from Trofymchuck, Glembockyte et al’s 2021 paper in Nature Communications.

The pathogen they used is Klebsiella pneumonia, which is resistant to antibiotics. There is a more-general overview of this work, as well as a more detailed paper:

Addressable nanoantennas with cleared hotspots for single-molecule detection on a portable smartphone microscope

How low is low-cost? According to the paper, the prototype cost about €4,200. The authors estimate that the price could be brought down to ca. €1,000 through higher-volume production.

Synthetic nanobodies for rapid development of virus antibodies

Whereas vaccines can prevent infection with a disease, antibodies can treat it. And it is often faster to develop and get approved new antibodies than vaccines.

A group of researchers at Sandia National Laboratories is using a relatively new technology, synthetic nanobodies, for rapid development of antibodies for new viruses. According to this article, “rapid development” means that a new antibody for a new virus can be developed within 90 days. And according to the same article, nanobodies have several advantages over traditional antibodies. For example, because they are smaller, they can penetrate tissues more thoroughly; they can be delivered as aerosols (which means they don’t have to be injected); and manufacturing them is easier and cheaper.

Part of the group’s toolbox are computational methods for predicting candidate molecules:

High-Throughput Virtual Screening of Small Molecule Inhibitors for SARS-CoV-2 Protein Targets with Deep Fusion Models

Detecting low-frequency pathogen variants

Basically by definition, new variants of a virus are rare initially. But if you want to prevent such new variants from spreading, you need to be able to detect them early on.

A group of researchers at Rice University in Houston, led by Todd Treangen, has published a new algorithm. This algorithm, called Variabel, is intended to detect such low-frequency pathogen variants. The code for Variabel is available on GitHub.

Importantly, Treangen and colleagues argue that Variabel can distinguish sequencing errors from actual virus variants.


Featured image by Science Photo Library.

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