Abstract: Since the outbreak of the new crown, people are either doing nucleic acid testing or on the way to do it. Based on the requirements of epidemic prevention and control, nucleic acid testing has become an indispensable means, but it has also brought many inconveniences to people's lives and increased the workload for medical staff. The mandatory requirements for 24-hour nucleic acid testing and 48-hour nucleic acid test results in the epidemic containment area mean that a new round of nucleic acid testing is carried out almost every day. If there is a new technology that can collect samples through blowing gas like drunk driving, and produce the new crown test results within 3 minutes, it is bound to reduce the manpower and material resources required for nucleic acid testing, save social resources, and help prevent and control the epidemic! Such products, there really are, and have been approved by the FDA.
FDA awarded EUA for COVID-19 testing equipment
Results can be produced in 3 minutes
On April 14, 2022, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the first COVID-19 diagnostic testing device (InspectIR, PNY-1000) (Figure 1). The device collects breath samples without the need for a nasopharyngeal swab, and the whole process takes less than 3 minutes. The device is close to a regular suitcase, easy to carry, and can be used in hospitals, public places, and mobile testing sites.
Figure 1 FDA authorized the first NEW CROWN breath testing device EUA (Source: FDA official website)
John Redmond, co-founder of InspectIR, said: "The demand for large-scale centralized COVID-19 testing in the workplace is increasing, and third-party COVID-19 nucleic acid testing is too time-consuming and cumbersome to be suitable for the workplace. The PNY-1000 is simple and easy to operate, making it ideal for workplace use. As long as the office puts one or two PNY-1000s, employees go to work like "punching in" to test it, and there are results in 3 minutes, almost no waste of time. It is not necessary to wait for a period of time to have a result, as with nucleic acid testing, which not only delays time, but also may lead to the spread of the virus. ”
1. Background of the equipment production company
The manufacturer of the device is Inspector Systems LLC ("InspectIR") under the trade name Ofitir COVID-19 Breathalyzer and the model PNY-1000. InspectIR was founded in 2018 with its registered office in Dallas, USA, and completed its seed round on November 26, 2019. InspectIR has partnered with the University of North Texas to develop portable, non-invasive opioid/marijuana/narcotic breath testing tools based on proprietary technology, creating the first portable tester for truly qualitative and quantitative narcotics.
Tim Wing, CEO of InspectIR, said: "For decades, the drug testing market has been based entirely on urine and blood analysis, and InspectIR's products will provide more detailed qualitative and quantitative results with results that are not only comparable to urine tests and blood test results, but also faster and can be presented in seconds. Our products will disrupt the narcotics testing industry by delivering the speed of detection of traditional missing detections for quick law enforcement. ”
2. Equipment principle
InspectIR is not limited to narcotic drug testing, the same technical route applies to COVID-19 testing. InspectIR has developed the PNY-1000 in 2020, and the subsequent testing and compliance process took nearly two years. With the FDA officially granting its EUA authorization, the detector can be applied to large-scale centralized COVID-19 inspection scenarios (Figure 2).
Figure 2 Appearance of PNY-1000 equipment (Source: FDA)
According to the FDA's InfluentialIR authorization, the PNY-1000 is essentially a VOC spectrum detector, a qualitative analysis device for the detection of five volatile organic compounds (VOC) metabolites associated with SARS-CoV-2 infection[1]. The PNY-1000 uses gas chromatography-mass spectrometry technology, which is regarded as the gold standard in the medical and judicial circles, to quickly and accurately detect the content of the above five organic substances from the breath of the subject as a criterion for determining whether to be infected with the new crown (Figure 3).
Figure 3 Schematic diagram of temperament combination (Source: Wikipedia)
In March 2022, The Lancet sub-journal eClinical Medicine published a paper titled "Detection of SARS-CoV-2 infection by exhaled breath spectral analysis: Introducing a ready-to-use point-of-care mass screening method" The results of the study (Figure 4) [2]. In this study, it was found that the breath of COVID-19 infected people contained aldehyde, ketones and alcohol gases, and these gases did not appear in the breath of patients with other mainstream conditions, even typical pneumonia, and were specific for COVID-19. This also provides a scientific basis for the development of PNY-1000, which can detect five kinds of organic matter known to be strongly related to new coronavirus infection: acetaldehyde, caprylylaldehyde, acetone, butanone and methanol.
Figure 4 Research results (Source: eClinical Medicine)
3. Equipment test results
According to the PNY-1000 test document released by the FDA, the test process for the PNY-1000 is that subjects should not eat, drink or use any tobacco products for 15 minutes before the test. First, the vacuum pump evacuation system vacuum-treats the 0.25L breath sample provided by the collected subject within 10 seconds. Subsequently, the breath sample interacts with a pre-concentrator in the system to collect and concentrate the sample, and the specific VOCs are detected by downstream residual gas analyzers. Finally, the algorithm is used to determine the VOCs and proportions present in the sample, and the SARS-CoV-2 test results are output: positive (+) and negative (-). The test results will be displayed on the instrument screen in less than 3 minutes. All positive test results must be subsequently confirmed by a highly sensitive SARS-CoV-2 test [3].
A sample of 2409 subjects was tested and found to be 91.2% accurate for positive testing and 99.3% for negative testing. Test samples include variants such as Delta and Omicron. This set of data proves that for subjects who are not infected with the new crown virus, the accuracy of the PNY-1000 test is very high, and the probability of "false positive" is very low; for positive infected people, the accuracy of this test method also meets the general requirements of public health agencies in many countries, including the United States, for rapid testing.
Conventional antibody testing has not been effective in avoiding the effect of antigen cross-reaction on the test results, and subjects infected with other epidemics (such as influenza caused by coronavirus) may lead to false positives in the new crown test, and precisely because the above volatile organic compounds are only associated with the new crown virus infection, antigen cross-reaction can be avoided. As a rapid detection method, the PNY-1000 has a detection accuracy of 99.3% for negative subjects, and the probability of false positives is very low. Although PNY-1000 performed well, the FDA also made it clear that this blow-in detection method is still not a substitute for nucleic acid testing, and positive results should be confirmed by additional nucleic acid testing.
4. Equipment price and time to market
On April 22, John Redmond said, "Currently each machine can only process about 20 samples per hour, so a lot of equipment is needed for large-scale screening." The first devices can take 10 to 12 weeks to go to market, and each test costs about $10 to $12. The FDA said it plans to produce about 100 devices a week, but it's unclear when that level will be reached. Some of the COVID-19 breath tests have already been tested in pilot projects or licensed for use in other countries, but the AspectIR Breathalyzer will be the first product to hit the market in the United States.
How experts and scholars evaluate
PNY-1000
Nathaniel Hafer, a molecular biologist at the Massachusetts Institute of Technology School of Medicine, said: "The PNY-1000 test for COVID-19 is impressively fast and accurate, and based on this technology, it is very valuable to expand the detectable virus types. ”
Cristina Davis, vice chancellor at the University of California, Davis, who has been working on coronavirus detection technology, said: "I think this is a very exciting development for the whole field of respiratory analysis, and this is a big step forward." ”
Dr Wilbur Lam, a pediatric haematologist and bioengineer at Emory University and the Georgia Institute, said: "We have been considering this type of testing for the entire pandemic and have also been waiting for licensed products and technologies, but only in practical applications can we really determine how useful the PNY-1000 will be." PNY-1000 doesn't give you a definitive diagnosis, it gives you a biochemical pattern associated with the disease. ”
Susan Butler-Wu, a clinical microbiologist at the Keck School of Medicine at the University of Southern California, said: "I would like to see more independent data on the performance of the PNY-1000 device, as well as more details on the compounds it detects." Volatile organic compounds are not well developed in the diagnosis of infections, and without more realistic data, I think it is too early to use them to diagnose patients. ”
Coronavirus testing is normalized
The antigen track has a bright future
There are two main ways to detect infectious diseases: to detect the pathogen itself or to detect antibodies produced by the body to fight the pathogen. Detection of pathogens can be used to detect antigens (usually pathogen surface proteins, some with internal nuclear proteins), and nucleic acids can also be detected. The test for the new crown virus is mainly divided into three types: nucleic acid detection, antigen detection, and antibody detection (Table 1). Among them, antigen detection reagents are simple to operate, fast detection speed, suitable for large-scale screening scenarios, and are currently widely used in overseas countries where the epidemic is more serious, and nucleic acid detection is currently the most effective detection method to determine whether to infect the new crown virus as soon as possible.
Table 1 Comparison of mainstream COVID-19 detection technologies
Source: Chinese Instrument Review 丨 Tabulation: Biological Exploration Editorial Team
New crown antigen testing, in the large-scale, rapid screening testing, has a high social value, residents can buy their own testing reagents, home self-test, exempt from the inconvenience of waiting for nucleic acid test results for a long time, reduce the risk of exposure in the testing process, but also solve the remote, grass-roots areas can not carry out nucleic acid testing difficulties.
On March 11, 2021, the National Health Commission released the news that the Comprehensive Group of the Joint Prevention and Control Mechanism of the State Council in Response to the Novel Coronavirus Pneumonia Epidemic decided to add antigen detection as a supplement to nucleic acid testing, and organized the formulation of the "Application Plan for New Coronavirus Antigen Detection (Trial)" (Figure 5). The complementary positioning of antigen testing has been further clarified, the "early detection" capacity has been improved, and the focus of use is on health institutions that do not have nucleic acid detection capabilities.
Figure 5 Notice of application plan for antigen detection of new coronavirus (trial) (Source: Official website of the Medical Administration)
According to statistics, the market size of diagnosis and treatment testing needs of primary medical and health institutions is about 5.5 billion yuan, the demand for isolation and observation personnel is about 2.5 billion yuan, and the demand for self-examination of community residents is about 24.9 billion yuan, with an overall total of more than 30 billion yuan. From a long-term perspective, assuming that after the social opening under the normalization of the new crown, according to the application scenarios of the new crown antigen detection, it is divided into static self-testing and dynamic large-scale detection, and on the whole, the market size of antigen detection under the long-term perspective can reach 270 billion yuan [4].
As of April 20, the NmPA has approved 29 test reagents for the new crown virus antigen. China's new crown antigen test self-test kit approval time is later than in Europe, the United States and other regions, and some mainland companies' antigen testing products have also been approved in Europe or the United States and marketed (Table 2). In the whole year of 2021, the total export value of China's new crown test kits (nucleic acid detection + antibody detection + antigen detection) is about 71.4 billion yuan, and the import countries are mainly Germany and the United Kingdom.
Table 2 Export enterprises of new crown testing reagents
Source: Company Announcements, NMPA 丨 Tabulation: BioExplorization Editorial Team
In the European market, there are more antigen detection reagent products for household detection, the price war is fierce, and the terminal price is about 2-3 euros. Taking Germany as an example, the products of the mainland's Aikang Biology, Anxu Biology, Wantai Biology, Heatscape Biology, Mingde Biology, Botuo Biology and other companies have been approved by the German Food and Drug Administration for household use, and other companies such as Wanfu Biological, Yahuilong, Oriental Biological, Lepu Biological and other products have also obtained CE certification.
In the US market, the FDA's approval of household COVID-19 antigen test kits is more stringent, and the market competition pattern is better, and only 5 companies in the mainland have obtained EUA in the United States, namely IKon Biologics, Jiuan Medical, Beadi, Biohan and Oriental Bio (oem for Siemens) (Table 3).
Table 3 Chinese-made COVID-19 test reagents obtained EUA
Source: FDA 丨 Tabulation: Biological Exploration Editorial Team
PNY-1000 is different from the previous technical route, which is bound to bring new changes to the new crown testing market. If it can really achieve high sensitivity, high accuracy and high cost performance, then PNY-1000 is also a good choice for NEW CROWN detection.
Written | essay competition
Typography | Muzijiu
End
Resources:
[1]https://www.fda.gov/media/157720/download
[2] Shlomo IB, Frankenthal H, Laor A, et al. Detection of SARS-CoV-2 infection by exhaled breath spectral analysis: Introducing a ready-to-use point-of-care mass screening method. EClinical Medicine. 2022 Mar;45:101308. doi: 10.1016/j.eclinm.2022.101308. Epub2022 Feb 19. PMID: 35224472; PMCID: PMC8856887.
[3]https://www.fda.gov/media/157723/download
[4] Special report on the new crown antigen testing industry: positioning and supplementation, opening a new space for the industrial chain - 20220313 - Huaan Securities. https://pdf.dfcfw.com/pdf/H3_AP202203141552507507_1.pdf?1647256503000.pdf
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