Device provides physicians with quick insights into infant’s immune system capabilities without requiring clinical laboratory testing
International researchers have developed a revolutionary tool that rapidly assesses an infant’s immune system using a single drop of blood. The novel device provides healthcare professionals with real-time insights about a newborn’s immune response in less than 15 minutes.
Scientists from the Singapore-MIT Alliance for Research and Technology (SMART) in collaboration with colleagues from KK Women’s and Children’s Hospital (KKH) in Singapore created the Biophysical Immune Profiling for Infants (BLIPI) portable device to help alleviate potentially life-threatening illnesses in newborns. The device only uses 0.05 ml of blood.
The work was led by researchers from the Critical Analytics for Manufacturing Personalized Medicine (CAMP) and Antimicrobial Resistance (AMR) interdisciplinary research groups within SMART. SMART is a major research collaboration between the Massachusetts Institute of Technology (MIT) and the National Research Foundation of Singapore.
“BLIPI represents a major step forward by providing clinicians with fast, actionable immune health data using a noninvasive method, where it can make a real difference for newborns in critical care,” said Kerwin Kwek Zeming, PhD, research scientist at SMART CAMP and SMART AMR, and co-lead author of the study, in an MIT news release.
“Our goal was to create a diagnostic tool that works within the unique constraints of neonatal care—minimal blood volume, rapid turnaround, and high sensitivity,” said Kerwin Kwek Zeming, PhD, research scientist at SMART CAMP and SMART AMR, and co-lead author of the MIT study, in the news release. (Photo copyright: MIT.)
Bridging Gap between Science and Healthcare
To perform their study, the team used BLIPI to screen 19 infants—eight full-term and 11 preterm—and compared the differences in immune cells between the infants. The device uses microfluidic technology to measure immune cell characteristics, such as size and flexibility, to expose how the immune system is responding to changes within the cells. Traditional tests look only for the presence of germs, but BLIPI also looks at results such as C-reactive protein levels, white blood cell counts, and immature-to-total neutrophil ratios, to determine if an infant is fighting an infection.
“BLIPI exemplifies our vision to bridge the gap between scientific innovation and clinical need. By leveraging microfluidic technologies to extract real-time immune insights from whole blood, we are not only accelerating diagnostics but also redefining how we monitor immune health in fragile populations,” said Jongyoon Han, PhD, professor of electrical engineering and biological engineering at MIT and coauthor of the paper, in the news release. “Our work reflects a new paradigm in point-of-care diagnostics: rapid, precise, and patient-centric.”
Saving Infant Lives
BLIPI only needs one tiny drop of blood, which equals 1/20 of the blood volume typical lab tests require. The onsite tool removes the need for sending blood samples to clinical labs, which may enable clinicians to make earlier decisions regarding treatment options for critical situations like sepsis or necrotizing enterocolitis.
“KKH cares for about two-thirds of all babies born weighing less than 1,500 grams (52.91 ounces or 3.31 pounds) in Singapore. These premature babies often struggle to fight infections with their immature immune systems. With BLIPI, a single prick to the baby’s finger or heel can give us rapid insights into the infant’s immune response within minutes. This allows us to tailor treatments more precisely and respond faster to give these fragile babies the best chance at a healthy start not just in their early days, but throughout their lives,” said Yeo Kee Thai, MD, senior consultant in the department of neonatology at KKH, and senior author of the study, in the news release.
BLIPI also could be extremely beneficial to healthcare settings in remote areas or with limited resources.
Further research and clinical trials are needed to validate the diagnostic accuracy of BLIPI. In addition, the researchers plan to improve the design to render it usable for widespread distribution. They also hope BLIPI will someday be used by pharmaceutical companies and medical researchers to evaluate immune responses to neonatal therapies in real time.
Hospitals in 38 states confirmed patient infections of the dangerous, drug-resistant fungus
Rapidly spreading Candida auris fungus is once again showing up in hospitals throughout the United States, with multiple cases confirmed in Georgia and Florida. Hospital laboratories and pathology departments are encouraged to take advantage of CDC resources to help in the diagnosis of this deadly pathogen.
Candida auris (C. auris) spreads between patients in hospital settings, is resistant to anti-fungal medications, and can cause severe illness, according to the Centers for Disease Control and Prevention (CDC). Tracking data from CDC’s National Notifiable Diseases Surveillance System found 4,514 new clinical cases of C. auris in the US in 2023.
“The number of clinical cases has continued to increase since the first US case was reported in 2016,” said the CDC of past outbreaks of C. auris. “Based on information from a limited number of patients, 30–60% of people with C. auris infections have died. However, many of these people had other serious illnesses that also increased their risk of death.” The fungus has been spreading at a high rate from 2016-2023 with several cases cropping up recently in Georgia.
According to representatives from the Georgia Department of Public Health, “the state has seen over 1,300 cases as of the end of February,” WJCL reported.
The Hill reports a significant recent increase in the spread of the fungus in all but 12 states. Though the number of cases in each state remains small, the overall percentage of increased cases is large and growing.
And a study conducted at Jackson Health System in Miami, Fla., and published in the American Journal of Infection Control, found that “The volumes of clinical cultures with C. auris have rapidly increased, accompanied by an expansion in the sources of infection.”
“If you get infected with this pathogen that’s resistant to any treatment, there’s no treatment we can give you to help combat it. You’re all on your own,” Melissa Nolan, PhD, associate professor of epidemiology and biostatistics at the Arnold School of Public Health, University of South Carolina, told Nexstar. (Photo copyright: University of South Carolina.)
CDC Recommendations
The deadly fungus was first detected in 2016 in US hospitals, and the number of cases in hospital patients has grown every year based on CDC data from 2023. Invasive medical procedures can provide a gateway for C. auris to infect patients, and the immunosuppressed nature of these patients can lead to further complications.
Invasive procedures that could expose a patient to C. auris include the placing of breathing and feeding tubes, and the insertion of vein or urinary catheters.
“We’ve had four people at one time on and off over the past few months, and in years past, it was unusual to have one or even two people with Candida auris in our hospital,” Timothy Connelly, MD, told WJCL about the spread of the fungus at Memorial Health in Savannah, Ga.
Cases have also rapidly increased in Miami according to the Jackson Health System study. The researchers found that, “The volumes of clinical cultures increased every year and infection sources expanded.”
The CDC considers C. auris “an urgent antimicrobial resistance threat” based on the severe risk an infected patient can face. “The rapid rise and geographic spread of cases is concerning and emphasizes the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control,” said Meghan Lyman, MD, in a CDC news release.
Fungal Infection is Difficult to Treat and Diagnose
C. auris has been shown to be resistant to antifungal medications, making it an acute threat to ill patients. And since it tends to infect already sick patients, it can be difficult to detect because symptoms of infection can be generic, such as fever or chills.
The fungus is also adept at surviving on hospital surfaces.
“It’s really good at just being, generally speaking, in the environment,” Melissa Nolan, PhD, associate professor of epidemiology and biostatistics at the Arnold School of Public Health, University of South Carolina, told Nexstar. “So, if you have it on a patient’s bed for example, on the railing, and you go to wipe everything down, if in whatever way maybe a couple of pathogens didn’t get cleared, then they’re becoming resistant. And so over time, they can kind of grow and populate in that hospital environment.”
CDC Resources to Help Identify C. auris
C. auris also can be misidentified with other candida species fungi. The CDC recommends identification using a diagnostic device “based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF).” The CDC also recommends using supplemental MALDI-TOF databases and molecular methods to help distinguish C. auris from other candida.
Prompt clinical laboratory diagnosis is extremely important to stem outbreaks as they become more frequent in hospital settings. The CDC offers resources for hospital pathology departments to aid in screening and detection.
“I think we need to do a better job of predicting,” Nolan told Nexstar. “Moving forward [we need] more funding to support quality surveillance of these potential infectious strains so that we can know in advance, and we can do a better job of stopping disease spread before it becomes a problem.”
According to the CDC, the fungus typically spreads in hospital settings and is not known to affect healthy people.
Innovative in-office test, when integrated with UTI microbiology testing performed by clinical laboratories, could contribute to better patient outcomes
Treatments for certain bacterial infections are becoming less effective due to antimicrobial resistance (AMR). Now, after a 10-year-long worldwide competition, the first multi-million euro prize for an accurate, rapid, and cost effective clinical laboratory test for diagnosing and treating urinary tract infections (UTIs) went to Sysmex Corporation’s subsidiary Astrego. This milestone event could benefit tens of millions of people who suffer from UTIs annually.
Astrego, of Uppsala, Sweden, won the €8 million (US$8.19 million) Longitude Prize on AMR for its PA-100 AST System. The new diagnostic technology will “transform treatment of urinary tract infections and brings the power of clinical laboratory testing into a doctor’s office,” according to a news release from Challenges Works, the United Kingdom-based organization that organized and awarded the prize.
The Astrego system is, according to Challenge Works’ website, a “game-changing solution” in “a novel point-of-care diagnostic test that rapidly and accurately identifies the presence of a bacterial infection and the right antibiotic to prescribe.”
“We launched the Longitude Prize on AMR (in 2014) to create the urgent ‘pull’ needed to get innovators working on one of the biggest life-and-death challenges facing humanity. Hundreds of teams [that] competed with multiple solutions [are] now close to market thanks to the prize,” said Tris Dyson, Managing Director, Challenge Works, in a news release.
The new diagnostic technology “could herald a ‘sea change’ in antibiotic use” according to the judges of the competition, The Guardian reported.
“The PA-100 AST System (above) creates a future where patients can quickly and accurately get a diagnosis and the correct treatment when they visit the doctor,” said Sherry Taylor, MD, UK National Health Service, Temple Fortune Medical Group, London, in the Challenge Works news release. “Accurate, rapid diagnosis of bacterial infections that help doctors and health workers to manage and target antibiotics, will slow the development and spread of antibiotic resistant infections, improve healthcare and save potentially millions of lives,” she added. In-office point-of-care systems like the PA-100 may reduce the number of doctor orders for UTI tests to clinical laboratories while contributing to better patient outcomes. (Photo copyright: Sysmex.)
How the Test Works
In the UK, people are treated for UTIs more than any other infection. It takes about three days for doctors to receive the results from traditional microbiology testing. They then prescribe an antibiotic to treat the infection. But about half of “infection-causing bacteria are resistant to at least one antibiotic,” according to a news release from the Geneva, Switzerland-based NESTA Foundation which funded the Longitude Prize on AMR.
“It’s impossible to overstate how critical it is to address AMR [antimicrobial resistance]. By 2050, it is predicted to cause 10 million deaths a year—matching those caused by cancer—and cost $1 trillion in additional health costs,” the news release states.
UTI are more common in women and the reason for eight million healthcare appointments annually in the US, according to Medscape.
The PA-100 AST system makes it possible for patients to provide a small urine sample during their appointments with doctors, find out if they have a bacterial infection in 15 minutes, and receive the “right antibiotic to treat it within 45 minutes,” NESTA said. Sysmex describes the PA-100 AST as an “automated phenotypic analyzer, based on EUCAST standards,” that combines “phase-contrast microscopy and nanofluidics to make available antibiograms at point of care.” It enables healthcare providers to perform antimicrobial susceptibility testing (AST) in-office rather than sending out urine samples to microbiology laboratories.
The systems works as follows, according to the Sysmex website:
As a urine sample passes through the chip, “single bacterial cells are trapped in individual channels.”
Meanwhile, “larger cellular components” are filtered and kept out of the nanofluidic chip.
Contrast-phase microscopy enables real-time monitoring of cell growth. “Resistant bacteria keep a higher growth rate during incubation, while susceptible ones grow slowly or lyse.”
Expert computer software identifies that bacterial strain, delivers an “easy to interpret antibiogram after assay completion” and provides an “informed prescription decision” on which antibiotic is expected to fight the infection.
“The PA-100 AST System challenges bacteria present in a patient’s urine with microscopic quantities of antibiotics in tiny channels embedded in a cartridge the size of a smartphone,” said Mikael Olsson, CEO and co-founder of Sysmex Astrego, in The Microbiologist.
“We rapidly pinpoint whether a bacterial infection is present and identify which antibiotic will actually kill the bugs, guiding doctors only to prescribe antibiotics that will be effective,” he added.
Sysmex is conducting more studies in the UK and working with regulators in Europe for clearances, according to Olsson.
Older Antibiotics May Make Comeback
It’s possible that use of the PA-100 system to identify the best antibiotic to treat infections could lead to a resurgence in the use of previously retired antibiotics.
“Roughly 25-30% of patients have infections resistant to older first-line antibiotics which have been retired as a result; this means the remaining 70-75% of patients could still benefit from those older drugs,” Pathology in Practice reported, adding, “Since the PA-100 AST System identifies which specific antibiotic can treat an infection, it will likely allow retired antibiotics to be brought back into service because the test is able to demonstrate when an infection is susceptible to their effects.”
Many people could benefit from the older antibiotics, Challenge Works noted.
Revolutionizing Healthcare
The Sysmex Astrego’s PA-100 AST System is a significant development.
“Currently, I send the urine sample off for analysis, and it usually takes around three days to come back with results,” said Sherry Taylor, MD, UK National Health Service, Temple Fortune Medical Group, London, in the Challenge Works news release. “Having a bedside test that would enable rapid diagnosis through antibiotic susceptibility testing would revolutionize general practice and patient care. It’s all about using antibiotics only when necessary and appropriate.”
Each individual test costs about €25 (US$25.72), The Guardian reported, adding that ramped up production may lower the price.
The PA-100 AST System is the latest example of a diagnostic/therapeutic solution developed in Europe rather than the US, which is often slower to award regulatory clearance.
It also is another test that will be performed outside of traditional clinical laboratory settings, demonstrating the trend to move medical laboratory tests closer to patients.
Diagnostic test incorporates artificial intelligence and could shorten the time clinical laboratories need to determine patients’ risk for antimicrobial resistance
Sepsis continues to be a major killer in hospitals worldwide. Defeating it requires early diagnosis, including antimicrobial susceptibility testing (AST), and timely administration of antibiotics. Now, in a pilot study, scientists at Seoul National University in South Korea have developed a new clinical laboratory test that uses artificial intelligence (AI) to pinpoint the condition sooner, enabling faster treatment of the deadly bacterial infection.
Sepsis, also known as septicemia or blood poisoning, is a serious medical condition that occurs when the body overreacts to an infection or injury. This often takes place in hospitals through blood-line infections and exposure to deadly bacteria. The dangerous reaction causes extensive inflammation throughout the body. If not treated early, sepsis can lead to organ failure, tissue damage, and even death.
Research teams around the world are creating new technologies and approaches to slash time to answer from when blood specimen is collected to a report of whether the patient is or is not positive for sepsis. The Seoul National University scientists’ new approach is yet another sign for microbiologists and clinical laboratory managers of the priority test developers are giving to solving the problem of diagnosing sepsis faster than using blood culture methodology, which requires several days of incubation.
“Sepsis strikes over 40 million people worldwide each year, with a mortality rate ranging from 20% to 50%,” said Sunghoon Kwon, PhD (above), professor of electrical and computer engineering at Seoul National University and senior author of the study, in an interview with The Times in the UK. “This high mortality rate leads to over 10 million deaths annually. Thus, accurate and prompt antibiotic prescription is essential for treatment,” he added. Clinical laboratories play a critical role in the testing and diagnosis of sepsis. (Photo copyright: Seoul National University.)
Reducing Time to Diagnosis
Seoul National University’s approach begins with drawing a sample of the patient’s blood. The researchers then attach special peptide molecules to magnetic nanoparticles and add those nanoparticles to the blood sample. The particles bind to the harmful pathogens in the blood.
The harmful bacteria are then collected using magnets. Their DNA is extracted, amplified, and analyzed to establish the type of microbes that are present in the sample.
The pathogens are exposed to antibiotics and an AI algorithm evaluates their growth patterns to forecast what treatments would be most beneficial to the patient. This last step is known as antimicrobial susceptibility testing or AST.
“The principle is simple,” said Sunghoon Kwon, PhD, professor of electrical and computer engineering at Seoul National University and senior author of the study, in a Nature podcast. “We have a magnetic nanoparticle. The surface of the magnetic nanoparticle we coat in a peptide that can capture the bacteria.”
Kwon is the CEO of Quantamatrix, the developer of the test.
The complete process can be performed on one machine and results are available in about 12 hours, which reduces typical AST time by 30 to 40 hours when compared to traditional processes.
“Sepsis progresses very quickly, with the survival rate dropping with each passing hour,” Kwon told The Times UK. “Every minute is crucial.”
Preventing Antimicrobial Resistance
The team assessed the performance of their test on 190 hospital patients who had a suspected sepsis infection. The test achieved a 100% match in the identification of a bacterial species. The test also achieved an efficiency of 96.2% for capturing Escherichia coli (E. coli) and 91.5% for capturing Staphylococcus aureus.
“Treatment assessment and patient outcome for sepsis depend predominantly on the timely administration of appropriate antibiotics,” the authors wrote in Nature.
“However,” they added, “the clinical protocols used to stratify and select patient-specific optimal therapy are extremely slow,” due to existing blood culture procedures that may take two or three days to complete.
“The microbial load in patient blood is extremely low, ranging between 1 and 100 colony-forming units (CFU) ml−1 and is vastly outnumbered by blood cells,” the study authors explained. “Due to this disparity, prior steps—including blood culture (BC) to amplify the number of pathogens followed by pure culture to subculture purified colonies of isolates—have been essential for subsequent pathogen species identification (ID) and AST.”
Further research, studies and regulatory approval are needed before this technique becomes available, but the South Korean scientists believe it could be ready for use within two to three years. They also state their test can help prevent antimicrobial resistance (AMR) and bolster the strength of existing antibiotics.
Previous Studies
The Seoul National University study is just the latest effort by scientists to develop faster methods for clinical laboratory testing and diagnosing of sepsis.
In September, Dark Daily reported on a similar test that uses digital imaging and AI to determine sepsis risk for emergency room patients.
According to the Centers for Disease Control and Prevention (CDC), at least 1.7 million adults develop sepsis annually in the US, and that at least 350,000 die as a result of the condition. CDC also lists sepsis as one of the main reasons people are readmitted to hospitals.
Microbiologists and clinical laboratory managers should be aware that scientists are prioritizing the creation of new testing methods for faster detection of sepsis. Various research teams around the world are devising technologies and approaches to reduce the time needed to diagnose sepsis to improve patient outcomes and save lives.
As this therapeutic approach gains regulatory approval, clinical laboratory tests to determine condition of patient’s gut microbiota and monitor therapy will be needed
Some developments in the clinical laboratory industry are less about diagnostic tests and more about novel approaches to therapy. Such is the case with a new carbon bead technology developed by researchers from University College London (UCL) and the Royal Free Hospital intended to remove harmful bacteria toxins from the gut before they leak to the liver. The macroporous beads, which come in small pouches, are delivered orally and could be utilized in the future to treat a number of diseases.
Why is this relevant? Once a new treatment is accepted for clinical use, demand increases for a clinical laboratory test that confirms the therapy will likely work and to monitor its progress.
In collaboration with Yaqrit, a UK-based life sciences company that develops treatments for chronic liver disease, the UCL and Royal Free Hospital scientists engineered the carbon beads—known as CARBALIVE—to help restore gut health. They measured the technology’s impact on liver, kidney, and brain function in both rats and mice.
“The influence of the gut microbiome on health is only just beginning to be fully appreciated,” said Rajiv Jalan, PhD, Professor of Hepatology at UCL in a press release. “When the balance of the microbiome is upset, ‘bad’ bacteria can proliferate and out-compete the ‘good’ bacteria that keeps the gut healthy.
“One of the ways [the ‘bad’ bacteria] do this is by excreting endotoxin, toxic metabolites, and cytokines that transform the gut environment to make it more favorable to them and hostile to good bacteria,” he continued. “These substances, particularly endotoxin, can trigger gut inflammation and increase the leakiness of the gut wall, resulting in damage to other organs such as the liver, kidneys, and brain.”
“I have high hopes that the positive impact of these carbon beads in animal models will be seen in humans, which is exciting not just for the treatment of liver disease but potentially any health condition that is caused or exacerbated by a gut microbiome that doesn’t work as it should,” said Rajiv Jalan, PhD (above), Professor of Hepatology, University College London, in a press release. “This might include conditions such as irritable bowel syndrome (IBS), for example, which is on the rise in many countries.” Though not a clinical laboratory diagnostic test, new therapies like CARBALIVE could be a boon to physicians treating patients with IBS and other gastrointestinal conditions.
Developing the Carbon Beads
The team discovered CARBALIVE is effective in the prevention of liver scarring and injury in animals with cirrhosis when ingested daily for several weeks. They also found a reduced mortality rate in test animals with acute-on-chronic-liver-failure (ACLF).
After achieving success with CARBALIVE in animals, the researchers tested the technology on 28 cirrhosis patients. The carbon beads proved to be safe for humans and had inconsequential side effects.
“In cirrhosis, a condition characterized by scarring of the liver, it is known that inflammation caused by endotoxins can exacerbate liver damage,” Jalan explained. “Part of the standard treatment for cirrhosis is antibiotics aimed at controlling bad bacteria, but this comes with the risk of antibiotic resistance and is only used in late-stage disease.”
The beads, which are smaller than a grain of salt, contain an exclusive physical structure that absorbs large and small molecules in the gut. They are intended to be taken with water at bedtime as harmful bacteria is more likely to circulate through the body at night which could result in damage. The carbon beads do not kill bacteria, which decreases the risk of antibiotic resistance. They eventually pass through the body as waste.
“They work by absorbing the endotoxins and other metabolites produced by ‘bad’ bacteria in the gut, creating a better environment for the good bacteria to flourish and helping to restore microbiome health,” said Michal Kowalski, M.Sc.Eng, Director and VP of Operations at Yaqrit, in the UCL news release.
“This prevents these toxins from leaching into other areas of the body and causing damage, as they do in cirrhosis,” he added. “The results in animal models are very positive, with reduction in gut permeability, liver injury, as well as brain and kidney dysfunction.”
Additional Research
The researchers plan to perform further clinical trials in humans to determine if the carbon beads are effective at slowing the progression of liver disease. If the benefits that were observed in lab animals prove to be compelling in humans, the technology may become an invaluable tool for the treatment of liver disease and other diseases associated with poor microbiome health in the future.
According to the American Liver Foundation, 4.5 million adults in the US have been diagnosed with liver disease. However, it is estimated that 80 to 100 million adults have some form of fatty liver disease and are unaware of it. Liver disease was the 12th leading cause of death in the US in 2020 with 51,642 adults perishing from the disease that year.
According to BMC Public Health, globally there were 2.05 million new cases of liver cirrhosis diagnosed in 2019. In that year, 1.47 million people around the world died from the disease.
More research and clinical studies are needed before this novel technology can be used clinically. When and if that happens, the demand for clinical laboratory tests that measure microbiome deficiencies and monitor patient progress during therapy will likely be high.
