Scholars from the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research initiative in Singapore, in collaboration with associates from KK Women’s and Children’s Hospital (KKH), have created a pioneering device to assess the immune capabilities of newborns.

By utilizing just one drop of blood, the BiophysicaL Immune Profiling for Infants (BLIPI) system delivers immediate insights into the immune reactions of newborns, facilitating the early identification of severe inflammatory ailments and permitting timely responses. This essential advancement addresses the pressing and unfulfilled demand for quick and minimally invasive diagnostic instruments to safeguard at-risk newborns, particularly those born before term.

Premature infants are exceedingly susceptible to life-threatening issues such as sepsis and necrotizing enterocolitis (NEC). Newborn sepsis — an infection in the bloodstream during the initial weeks of life — poses a significant global health issue, leading to approximately 1 million infant fatalities annually worldwide. NEC, a critical gastrointestinal disorder that induces severe inflammation, ranks among the primary causes of mortality in premature babies — up to 50 percent of low-birth-weight newborns affected by NEC do not survive. Infants can exhibit nonspecific symptoms, complicating the diagnosis of these conditions. Nonetheless, both conditions can escalate quickly and necessitate urgent medical action for optimal recovery chances.

Existing diagnostic techniques to identify and prevent these serious conditions in newborns depend on substantial blood samples — up to 1 milliliter, a considerable amount for a newborn — and protracted laboratory procedures. This approach is unsuitable for newborns, whose total blood volume may be merely 50 ml in extremely premature infants under 28 weeks, thereby limiting repeated or high-volume sampling, potentially leading to anemia and other challenges. Simultaneously, conventional assessments — such as blood cultures or inflammatory panels — could take several hours to days to yield actionable conclusions, restricting swift targeted clinical interventions. The innovative BLIPI device tackles these issues by necessitating only 0.05 ml of blood and providing results within 15 minutes.

In a study titled “Whole blood biophysical immune profiling of newborn infants correlates with immune responses,” appearing in Pediatric Research, the researchers illustrated how BLIPI employs microfluidic technology to evaluate the alterations in immune cells during infection by analyzing their size and flexibility. Unlike traditional tests that solely assess the presence of pathogens, BLIPI directly indicates how a newborn’s immune system is reacting. The cell modifications detected by BLIPI correspond with standard assessments used by physicians, including C-reactive protein levels, white blood cell counts, and immature-to-total neutrophil ratios. This testing approach can swiftly indicate whether a newborn’s immune system is combating an infection.

In the study, BLIPI was utilized to assess 19 infants at various time intervals — eight full-term and 11 preterm — and revealed distinct differences in the appearance and behavior of immune cells among the infants. Remarkably, when one preterm infant developed a severe blood infection, the device successfully identified significant changes in immune cells. This highlights its potential to detect infections early.

The investigation was directed by scholars from the Critical Analytics for Manufacturing Personalized-Medicine (CAMP) and Antimicrobial Resistance (AMR) interdisciplinary research groups within SMART.

BLIPI is a compact device capable of providing results at the ward or neonatal intensive care units, eliminating the necessity of transporting blood samples to the laboratory and facilitating its straightforward implementation in resource-limited or rural health-care environments. Notably, BLIPI requires merely one drop of blood, and one-fifth of the blood volume that current methods demand. These rapid results can assist clinicians in making timely, life-saving decisions in critical scenarios such as sepsis or NEC, where prompt treatment is crucial.

“Our objective was to design a diagnostic tool that functions within the unique limitations of neonatal care — minimal blood volume, rapid turnaround, and heightened sensitivity. BLIPI signifies a major advancement by furnishing clinicians with swift, actionable immune health data through a noninvasive mechanism, where it can significantly impact newborns in critical care,” comments Kerwin Kwek, research scientist at SMART CAMP and SMART AMR, and co-lead author of the investigation.

“BLIPI embodies our vision to connect scientific innovation with clinical requirements. By harnessing microfluidic technologies to derive real-time immune insights from whole blood, we are not only expediting diagnostics but also redefining how we monitor immune health in fragile populations. Our work signifies a new paradigm in point-of-care diagnostics: rapid, accurate, and patient-focused,” expresses MIT Professor Jongyoon Han, co-lead principal investigator at SMART CAMP, principal investigator at SMART AMR, and corresponding author of the publication.

“KKH oversees nearly two-thirds of all infants born weighing less than 1,500 grams in Singapore. These premature infants frequently struggle to resist infections due to their immature immune systems. With BLIPI, a single prick to the baby’s finger or heel can provide us rapid insights into the infant’s immune response within minutes. This enables us to customize treatments more precisely and respond more swiftly to offer these vulnerable infants the best chance at a healthy beginning not only in their early days but throughout their lives,” comments Assistant Professor Yeo Kee Thai, senior consultant at the Department of Neonatology at KKH, and senior author of the study.

Future investigations will center on larger clinical trials to validate BLIPI’s diagnostic precision across varied neonatal populations with different age groups and medical conditions. The researchers also aim to enhance the device’s design for extensive adoption in hospitals worldwide, providing a crucial diagnostic solution for at-risk infants at their bedside. Beyond hospitals, pharmaceutical companies and researchers might also utilize BLIPI in clinical trials to evaluate immune responses to neonatal therapies in real-time — a potential game-changer for research and development in pediatric medicine.

The research conducted at SMART is backed by the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise program. This collaboration illustrates how Singapore unites institutions in interdisciplinary, multi-institution endeavors to advance technology for global influence. The contributions from KKH were partially supported by the Nurturing Clinician Scientist Scheme under the SingHealth Duke-NUS Academic Clinical Programme.