SMART is developing a rapid deterministic lateral displacement test to assess the immune response

The new unlabeled test uses unconventional L and inversely shaped L pillars of microfluidic deterministic lateral displacement (DLD) technology to quantify and profile white blood cell (WBC) immune states by assessing the biophysical properties of size, deformation, distribution, and cell count

The test requires only 20 microliters (μl) of unprocessed blood and takes only 15 minutes – much faster than existing methods that require up to 15 milliliters (ml) of blood and takes at least a few hours to get results

This new technology measures and profiles the often volatile immune response of the host, resulting in a more accurate assessment of the patient’s pathophysiology.

Current methods of early diagnosis of infection focus on the detection of pathogens with low abundance and are long-lasting, low susceptibility and do not accurately reflect the severity of the infection

Singapore, March 25, 2021 – Researchers from Critical Analytics for Personalized Medicine Production (CAMP), the Interdisciplinary Research Group (IRG) at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s Singapore Research Company, have developed a new an unlabeled immunological profiling test that profiles rapidly altering host immune responses in the event of infection, in contrast to existing methods that focus on detecting the pathogens themselves, which can often be at low levels within the host. This new technology offers many advantages over current methods, at the same time much faster, more sensitive and more accurate.

The new analysis is described in a paper entitled “Labelless Biophysical Markers from Microfluidic Immune Profiling of Whole Blood Reveals Serious Signatures of the Immune Response,” published recently in Small, a weekly peer-reviewed scientific journal covering nanotechnology, and included a pilot study of 85 recruited donors. from the emergency department of the National University Hospital (NUH). The work was led by dr. Kerwin Kwek Zeming, Senior Postdoctoral Fellow at SMART CAMP, and co-authors are Professor Jongyoon Han, Principal Investigator at SMART CAMP and Professor of Biological Engineering and Electrical Engineering at MIT, and others. Win Sen Kuan, Director of Research, Emergency Medicine Service, NUH.

In many cases, the main culprit for the manifestation of the disease, the severity of the infection and the mortality of the patients is the overly aggressive immune response of the host. For example, the Spanish flu pandemic of 1918 resulted in a disproportionately large number of deaths among otherwise healthy young adults. This is attributed to the now well-studied phenomenon of cytokine storms, which accelerate the rapid release of immune cells and inflammatory molecules, and stimulate them by the hyperaggressive immune response of the host. In a more recent example, cases of severe COVID-19 infection often result in death due to sepsis and impaired immune response, while current risk stratification methods based on age and comorbidity remain a significant challenge and may be inaccurate. Moreover, current Covid-19 testing does not predict the severity of the immune response and thus may lead to inefficient resource allocation in healthcare facilities.

In cases of acute infection, the status of the patient’s immune response can often be unstable and can change within minutes. Therefore, there is an urgent need for tests that can quickly and accurately inform about the state of the immune system. This is especially important in early triage in patients with acute infection and in predicting the subsequent worsening of the disease. In turn, this will better empower medical staff to make more accurate initial assessments and provide an appropriate medical response. This can ensure timely intervention in the emergency department (ED) and prevent admission to the intensive care unit (ICU).

A new test developed by SMART researchers focuses on profiling a rapidly changing host inflammatory response, which in a hyper-aggressive state can lead to sepsis and death. A 15-minute unlabeled immunoprofiling test was developed with 20 μL of untreated blood using unconventional L-pillars and an inverse form of DLD microfluidic technology, which function as a sensitive and quantitative test of biophysical immune cell signatures versus real-time WBC activation levels. As WBCs are activated by a variety of internal or external triggers, the test can sensitively measure the extent and direction of these changes, which in turn reflects the current state of the patient’s immune response. As such, a new test developed by SMART researchers is able to accurately and quickly assess patients’ immune response states by profiling immune cell size, deformability, distribution, and cell number.

Significantly, the new test provides significant advantages over existing methods of profiling the immune system and its activity. These include measuring the expression of leukocyte genes, biochemical markers on the cell surface and the profile of cytokines in the blood serum. Significantly, these current methods require sample dilution or pre-treatment steps, as well as labor-intensive, expensive equipment and antibody labeling procedures. As a result, these methods usually take at least a few hours to recover. This is a key point of pain and a lack of triage and emergency services, where clinicians must make accurate clinical assessments as soon as possible. The nature of these current methods related to work and time significantly limits their clinical utility for rapid triage and prevents their wider application in ER or ICU.

Conversely, since this new SMART test lasts only 15 minutes, uses only 20 μL of solid blood, and requires only video recording speeds of up to 150 fps, there is significant potential for technology to evolve into a portable unit that can perform on-site blood-saving tests. care that could significantly improve the diagnosis and differentiation of patients in emergencies and other primary or critical care settings. This application will allow clinicians to quickly identify at-risk patients and take immediate action to alleviate or prevent organ dysfunction and other adverse effects of a hyper-aggressive immune response.

Leading author dr. Kerwin Kwek said, “Our new DLD test will help address unmet needs in the emergency and Internet unit by significantly reducing waiting times for accurate patient test results. This could lead to more efficient triage decisions and more appropriate and timely treatment, which are crucial In general, this revolutionary technology provides new insights into both precision microfluidic engineering and clinical research. “

Professor Jongyoon Han added: “After lessons learned in emergency services in hospitals around the world, especially during the COVID-19 pandemic, where medical workers faced difficult and sometimes life-or-death decisions in triage, this new technology By reducing the time required for test results from hours to minutes, the new SMART CAMP test could help save lives as we continue to fight the scourge of pathogens and infectious diseases.they also have a wider application, providing clinicians with a new and a more efficient tool in the emergency and Internet unit. “