Vol.1 「Johns Hopkins University developed a gonorrhea rapid diagnostic test platform "PROMPT" 」
Last Updated 9 June 2023. Cellspect Co., Ltd.
A Johns Hopkins University-led team has developed an inexpensive, portable device and mobile app that can diagnose gonorrhea in less than 15 minutes and determine whether specific strains are becoming resistant to frontline antibiotics. The invention improves upon traditional tests in hospital laboratories and clinics, which typically take up to a week for results. The results were published in the journal Science Translational Medicine.
More than 87 million people worldwide are infected with gonorrhea, a potentially devastating sexually transmitted disease that is increasingly resistant to antibiotics. Quickly identifying and treating infected people is the only way to prevent a surge in case numbers and a further increase in antibiotic-resistant strains, experts say.
PROMPT (portable, rapid, on-cartridge, magnetofluidic purification and testing platform), a new device runs on a simple 5-volt battery, includes a thermoplastic case that costs about $2, and measures just 12.7 cm x 13.4 cm x 8.4 cm.
The PROMPT test is carried out by simply mixing a swab containing a patient's body fluid sample with a solution of magnetic particles in a tube, then places a drop of the mixture into a cartridge and snaps it into a PCR reaction device. Diagnostic results are then available in less than 15 minutes. The overall sensitivity and specificity of gonorrhea detection were 97.7% and 97.6%, respectively, and concordance with ciprofloxacin-resistant culture results was 100% (ciprofloxacin is a medication that targets infections that are resistant to other antibiotics.)
In simple terms, PROMPT, a device for detecting gonorrhea, maintains the same sensitivity and specificity currently used in hospital and clinic laboratories, but reduces the costs and time involved. It ensures patients are diagnosed on the spot and treatment can begin immediately, improving clinical outcomes. This is especially valuable in low-resource settings where not all patients have access to well-equipped laboratories. Its ability to rapidly identify gonorrhea and characterize its antimicrobial susceptibility has important implications for advancing antimicrobial stewardship and reducing selection pressure on antimicrobial resistance.
【Photo of PROMPT】Image credit: reference 1
ALEXANDER Y. TRICK et al., May, 2021 “A portable magnetofluidic platform for detecting sexually transmitted infections and antimicrobial susceptibility” SCIENCE TRANSLATIONAL MEDICINE Vol 13, Issue 593 DOI: 10.1126/scitranslmed.abf6356
Lisa Ercolano, May, 2021 “Johns Hopkins develops portable device for rapidly diagnosing STIs” Johns Hopkins University hub.
Vol.2 「A Patch-Type Device for Continuous Measurement of Glucose, Alcohol, and Lactate is Coming Close to Commercialization 」
Last Updated 7 July 2023. Cellspect Co., Ltd.
In May 2022, engineers at the University of California in the United States have developed a wearable patch-type device (a next-generation portable device) that can constantly measure glucose, alcohol and lactate levels in the body. Simply by attaching it to the arm, an ultrafine needle (microneedle) about 0.1 mm across the surface of a patch about 3 cm in diameter can measure the body fluid in the epidermis and sends the results to a smartphone. It's the first wearable device that can measure multiple items simultaneously, and can track changes in each value in real time, giving you an idea of how much you eat, drink and exercise.
When the patch is attached to the skin, the enzyme contained in the tip of the microneedle reacts with glucose, alcohol and lactate in the body fluid to generate a small electric current. The concentration of each item is determined by the strength of current flows through each needle. Measurement data is sent to the phone via Bluetooth and stored within the app.
The characteristics of microneedle-type wearables are that the needles about one-fifth the width of a human hair, so there is almost no injection-like pain, and wireless communication is used so there are no restrictions on body movement. Unlike one-off measurements, it can track values continuously, making it easier to understand when a value rises and identify the cause of the rise.
Traditional wearable devices are lack of the ability to measure multiple items simultaneously. Until now, only one item could be measured, such as a continuous glucose monitor or alcohol breathalyzers.
For example, drinking raises the blood alcohol levels in the blood and lowers blood sugar levels, making diabetics more susceptible to hypoglycemia. The device will tell you how much alcohol concentration will lower your blood sugar by how much, so you can get an idea of how much to drink.
Also, there is no device that can continuously measure lactate levels. Elevated lactate levels represent muscle fatigue, so it is an important index to prevent injuries caused by overtraining for athletes.
Since excessive lactate production during intense exercise (anaerobic exercise) acidifies the blood, causing hyperventilation, hypotension, dehydration, and hypothermia in diabetics, devices that constantly measure lactate levels are also in demand in the medical field.
The results measured with the device were the same as those of general examinations performed at hospitals, so it can be used with confidence.
However, since the current measurement time is 5 ~ 6 hours, the company will improve the system so that it can measure continuously for several days or weeks, adding more measurement items before commercializing it.
An example of an item that requires continuous measurement is the LH (luteinizing hormone), which increases rapidly one to two days before ovulation and returns to its original level quickly. It's used as a timekeeping method of getting pregnant, but the only one way to measure it is with urine, and there's a risk of missing the rising time.
With the number of infertility treatments increasing these days, there is a high demand for wearable devices that can continuously measure LH hormones. Therefore, it is very much looking forward to it being included in the inspection project.
A device that can measure sugar, alcohol and lactate levels simply by attaching it to the arm (Photo credit: University of California San Diego news page).
It consists of electronic sensors, batteries, Bluetooth devices and other built-in components (left), and a disposable microneedle array (right) (Photo credit: University of California San Diego news page).
Farshad Tehrani et al., May, 2022 “An integrated wearable microneedle array for the continuous monitoring of multiple biomarkers in interstitial fluid” Nature Biomedical Engineering volume 6, pages1214–1224
Liezel Labios, May 09, 2022 “Multi-Tasking Wearable Continuously Monitors Glucose, Alcohol, and Lactate” UC San Diego News.
Vol.3 「Improve the performance of lateral flow analysis to PCR level within 3 minutes」
Last Updated 10 August 2023. Cellspect Co., Ltd.
Rapid testing is one of the best strategies to deal with epidemics such as COVID-19. Currently, PCR testing is still considered as the gold standard for the diagnosis of COVID-19. However, PCR is costly, time-consuming (4-6 h), and difficult to achieve frequent testing. Lateral flow assays (LFA) are currently considered as the best platform for rapid testing because they are not only convenient but also meet the World Health Organization (WHO) "ASSURED" criteria (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free and Deliverable to end-users). Recently, a research team from South Korea published an enrichment tool, BEETLES2 in the journal Nature Communications, which can enhance the sensitivity and specificity of LFA and achieve almost the same accuracy as PCR.
BEETLES2 is a membrane composed of red blood cell membrane and nanoporous Anodic Aluminum Oxide (AAO) membrane. The honeycomb nanostructured AAO membrane with aligned 20 nm pores has no permeation selectivity and is only responsible for size-based separation, allowing various larger proteins such as albumin, viral proteins, and immunoglobulins to pass through. The red blood cell membrane is covered on the AAO membrane as a physical barrier, and it has permeation selectivity when the applied pressure is >0.5 bar. Such a combination allows the enrichment from various samples based on pressure, molecular size, surface charge and buffer conditions. The research team used the samples from COVID-19 patients and was able to enrich whole virus, N protein and immunoglobulin G (IgG) antibodies within 3 minutes. The limit of detection was also increased by 20 times. When the enriched samples were applied to other assays, such as LFA and PCR, all showed enhanced diagnostic sensitivity, specificity and accuracy.
The research team also used clinically low viral load (Ct ≥ 30) samples to support the evidence. The sensitivity of general LFA detection will be greatly reduced when encountering low viral load samples. For samples such as swabs or saliva with low viral load, the sensitivity of commercial LFA is about 14.29%, and the sensitivity of samples concentrated by BEETLES2 can be increased to 90%. Whereas the colorimetric signal from the healthy control group showed 100% specificity. In addition, since the N protein and IgG properties of influenza A/B are similar to those of SARS-CoV-2, BEETLES2 may also be applicable to influenza A/B or other target viruses. Similar to the COVID-19 antigen test, an enhanced colorimetric signal was obtained through the sample concentration process.
The BEETLES2's ability to enrich samples provides strong permeation selectivity and tunability, while being easily combined with current commercial LFAs to increase their sensitivity and accuracy. Such a combination of advantages represents an advancement in POCT testing, as it meets all the World Health Organization requirements for POCT, namely ease of use, low cost, and accuracy. However, in order to commercialize BEETLES2, there are still some problems that need to be solved, such as withstand voltage design, reducing the amount of samples required, and prolonging the storage stability at room temperature.
（Photo)「BEETLES2」Image credit: reference 1
Seong Jun Park et al., May, 2023 “PCR-like performance of rapid test with permselective tunable nanotrap” Nature Communications volume 14, Article number: 1520
Vol.4 「Glowstick inspired scientists to develop new POCT applications」
Last Updated 15 September 2023. Cellspect Co., Ltd.
Lateral flow immunoassays (LFAs) are rapid and convenient point-of-care diagnostic applications that have played a pivotal role in the COVID-19 pandemic. But its sensitivity is limited, and is often able to detect single analyte, so scientists are still working on improving this technique. Recently, a research team from the University of Houston published an article entitled "Glowstick-inspired smartphone-readable reporters for sensitive, multiplexed lateral flow immunoassays" in the journal Communications engineering. In this study, the authors demonstrate glowstick-based LFA (Glow-LFA) that do not require optical excitation, are excited using low-toxicity and odor chemicals, and are compatible with nitrocellulose membranes and common clinical samples.
Briefly, the authors used chemical excitation to replace the optical excitation in traditional glowsticks. Therefore, Glow-LFA resembles the conventional enzymatic-based LFA workflow but without requiring the use of fragile enzymes or expensive and temperature-sensitive light-generating chemiluminescent substrates, and does not require the expensive or complex optics used for fluorescent LFAs. Chemically excited fluorescent particles that generate visible light can be detected by smartphones, increasing sensitivity while remaining simple and cost-effective. The authors also further screened the TCPO solvent and H2O2 co-solvent to maximize the intensity and stability of the signal while reducing toxicity and odor. The common model analyte human chorionic gonadotropin was detected with this Glow-LFA with a limit of detection of 39 pg/ml, more than 10 times more sensitive than standard gold nanoparticles using the same antibody. This method can also be applied clinically to detect SARS-CoV-2 nucleoprotein in nasal swab samples, achieving a sensitivity of 100 pg/mL, which is far superior to the current LFA technique. Simultaneously, this Glow-LFA can chemically excite multiple fluorescent dyes by one reagent, allowing multiplex analysis on a single LFA strip. The detection of three analytes in one LFA detection line utilizes red, green, and blue fluorescent reporter particles, making Glow-LFA a promising multiplex detection platform.
Although there are still some manual steps in this method that need to be simplified, such as mixing reagents (like glowsticks) to activate reagents, and applying the mixture on LFA strips, etc. The research team's ultimate goal is to store reagents in vesicles into the cartridge and deliver them via push to the LFA strip, limiting user exposure to the reagents and simplifying the analytical workflow. Unlike other high-sensitivity LFA reporter technologies, Glow-LFA increases the sensitivity of analyte detection without compromising simplicity and POCT applicability.
Figure 1 (quoted from the article “Cellspect develops antigen test kits for coronavirus and influenza” published in Nihon Keizai Shimbun December 9, 2020)
Figure 2 (Image credit：http://monta.moe.in/wp/2014/01-12/14-58_1412）
Figure 3 (Image credit：reference 1)
Kristen Brosamer et al., 23 June, 2023 “Glowstick-inspired smartphone-readable reporters for sensitive, multiplexed lateral flow immunoassays” Communications Engineering volume 2, Article number: 31
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