Researchers are developing a 15-minute test to assess the immune response

Close up of a microfluidic DLD test chip with a $ 1 Singapore coin per scale. Credit: Singapore-MIT Alliance for Research and Technology

Researchers from Critical Analytics for Manufacturing Personalized-Medicine (CAMP) have developed a new unlabeled immune profiling test that profiles a rapidly changing host immune response in the event of infection, in contrast to existing methods focused on detecting pathogens themselves, which can often be 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.

A 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 donors recruited 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 were 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, Department of Emergency Medicine, 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 testing for COVID-19 does not predict the severity of the immune response and thus may lead to inefficient resource allocation in health 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 assay with 20 µL of untreated blood was developed using unconventional L and inversely shaped pillars of DLD microfluidic technology, functioning 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 working-time nature of these current methods 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 department and emergency department by significantly reducing waiting times for accurate patient test results. This could lead to more efficient triage decisions and more appropriate and timely decisions that are crucial for saving lives. In general, this revolutionary technology provides new insights into both precision microfluidity 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. ”

COVID-19: Biomarkers associated with severe forms of the disease

More information:
Kerwin Kwek Zeming et al. Labelless biophysical markers from whole blood microfluidic immune profiling reveal serious signatures of the immune response, Small (2021). DOI: 10.1002 / smll.202006123

Journal information:

Provided by the Singapore-MIT Alliance for Research and Technology

Citation: Researchers Develop 15-Minute Immune Response Assessment Test (2021, March 25) Retrieved March 25, 2021, from

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