Increasingly, infections pose complex problems for clinicians, especially those treating patients in the ICU. While they want to treat patients with pneumonia or bacteremia with the right antibiotic—and not contribute to growing antibiotic resistance—often they must wait days before they’ll know which pathogen patients have and the right drug to use. For patients who are very ill, empiric therapy has serious risks.
Pattern Bioscience is tackling this problem with technology that enables single-cell microbiology that both detects a pathogen and determines antibiotic susceptibility in as little as 4 hours, instead of the 2–4 days typically required. For this, they won the 2023 Association for Diagnostics & Laboratory Medicine (ADLM, formerly AACC) Disruptive Technology Award competition, the result of which was announced in July at the 2023 AACC Annual Scientific Meeting.
“It reduces the interval of diagnostic uncertainty for patients who have an infection, so clinicians can get them on the correct treatment, if treatment is even needed” by the time a second dose of antibiotics would be administered, said Carey-Ann Burnham, PhD, Pattern Bioscience chief clinical officer. That’s because antibiotics are typically dosed about every 8 hours. If a patient receives broad-spectrum antibiotics upon admission, the company’s device can identify the pathogen and the right antibiotic before the time comes up for the second dose. “That’s why it’s so important in a hospital setting. We’re targeting critically ill patients initially,” Burnham said.
The testing platform uses precise microfluidics. A sample is divided into tiny droplets, which contain either a single bacterium or none. Those droplets then flow into “zones” and interact with zone-specific reagents. Every zone also has two metabolic dyes. Together, this creates a metabolic signature.
Instead of measuring genetic targets associated with resistance, Pattern uses artificial intelligence (AI) to measure the response of bacteria cells to antibiotics. The system can both identify what pathogen is present and rule-in specific antibiotics—if antibiotics are appropriate at all.
The instrument is the size of a breadbox, with each cartridge about the size of a thick sandwich. Fully loaded, the system can process 22 samples simultaneously. The configuration of the testing mechanism means the test is not limited to monomicrobial samples. It can also analyze samples from complex clinical specimens, including nonsterile body sites where pathogens often mix with normal microbiota. “Because we put them into droplets and measure different droplets, they become their own incubation chamber, and we can look at polymicrobial samples,” she said.
Pattern Bioscience’s platform depends on advances in both material and computer science. “A big part of it is the ability to make the droplets,” Burnham said, made possible in part because of new kinds of plastics. Better and faster machine learning is also key because it can assess reactions much faster. “The algorithm takes into account where and how a microbe is growing, in addition to the metabolic pattern,” she said. “It’s very similar to what microbiologists do today when they look at agar plates.”
But Pattern has strict controls on how the AI works. The company limits what pathogens it looks for to what is most likely to be present in the patient. “The cartridge doesn’t ID every microorganism under the sun,” Burnham said. If it’s beyond the scope of what the technology looks for, it’s tagged as an “unidentified organism,” which means additional testing is needed.
In 2021, the company’s Pneumonia Action Panel received a Food and Drug Administration breakthrough device designation to be used for hospitalized patients with pneumonia. It’s the first and only emerging technology that can comprehensively diagnose pneumonia directly from a clinical specimen.
Pattern chose to focus on pneumonia and bacteremia first because of the platform’s ability to detect the range of pathogens and normal microbiome in the respiratory tract. They felt this was where they could make an immediate and impactful difference. Pneumonia complicated by septic shock is a leading cause of morbidity and mortality, and 51% of patients with pneumonia complicated by septic shock die in the U.S.
For antimicrobial stewardship, it could be a game changer, Burnham said. “The longer a patient stays on the wrong antibiotic, the higher the chance of mortality,” she said. “This gives definitive information to help people get onto the most appropriate antibiotic. In a lot of cases, it means no antibiotic.”
She sees this as a benefit to patient outcomes and patient experience. “People are eager to have an answer,” she said. “It’s a good patient satisfier to be able to move more quickly and say, ‘You have this, you don't have this...treatment.’”
Right now, the Pattern platform is a moderately complex test under CLIA rules and must be performed in a CLIA-certified laboratory. But the company also sees a much wider range of potential uses, and it plans to follow this panel with those that look at blood cultures, then urine. The goal is for their device to become even more simple and reliable, so that it can become a point-of-care test used by almost anyone.
Burnham came to Pattern Bioscience in 2022, after working as professor of pathology and immunology, molecular microbiology, pediatrics, and medicine at Washington University School of Medicine in St. Louis, and as the medical director of clinical microbiology at Barnes-Jewish Hospital. Over 15 years in academia, she saw how innovations continually changed laboratory medicine, especially MALDI-TOF mass spectrometry. A desire to see even greater advances in her field led her to Pattern Bioscience.
Ultimately, Burnham believes that their work will “change the way clinical microbiology is practiced. It gives results comparable to the gold standard,” she said. She also believes that the company can engineer the system to produce results even faster.
Jen A. Miller is a freelance journalist who lives in Audubon, New Jersey. +Twitter: @byJenAMiller
ADLM considered many innovative and cutting edge technologies for its Disruptive Technology Award competition. Here are the two other finalists.
MS PEN TECHNOLOGIES
This medical technology company is working to bring the power of mass spectrometry to a broader base of users, in a smaller and more manageable form. They’re doing so through Ultiss (short for ultimate surgical sensing system), a medical platform that uses their MasSpec Pen to directly analyze tissue and other samples in seconds. The device itself is designed as a handheld or minimally invasive probe, and acts as an interface between a nonexpert user and mass spectrometer. The company said it hopes that their device and platform will bring the power of mass spectrometry to more people.
VitalOne is a platform that, with 600 uL of blood, quantifies more than 50 of the most ordered biomarkers in primary care—and does it in only 20 minutes. The system does so using an automated microfluid workflow, with the instrument running on three subsystems at the same time: hematology, clinical chemistry, and immunoassays. In its current form, VitalOne spans a wide range of potential use cases for the general population, including inflammation, cardiac markers, diabetes, and liver disorders. The company is currently building a menu that they say will cover 100% of the tests needed for at least 90% of patients.