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Label-free Immune Profiling Assay to Assess Immune Response

Novel DLD assay is capable of rapidly assessing host inflammatory response, allowing patients exhibiting a life-threatening hyper-aggressive immune response to be identified and treated expeditiously, and thus potentially making the difference between life or death.

In cases of acute infection, the status of a patient’s immune response can often be volatile and may change within minutes. Hence, there exists a pressing need for assays that are able to rapidly and accurately inform on the state of the immune system. This is particularly vital in early triage among patients with acute infection and prediction of subsequent deterioration of disease. In turn, this will better empower medical personnel to make more accurate initial assessments and deliver the appropriate medical response. This can ensure timely intervention in the emergency department (ED) and prevent admission to the intensive care unit (ICU).

Researchers from Critical Analytics for Manufacturing Personalized-Medicine (CAMP), an Interdisciplinary Research Group (IRG) at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have developed a new label-free immune profiling assay that profiles the rapidly changing host immune response in case of infection, in a departure from existing methods that focus on detecting the pathogens themselves, which can often be at low levels within a host. This novel technology presents a host of advantages over current methods, being both much faster, more sensitive and accurate.

The new assay is described in a paper titled, “Label-free biophysical markers from whole blood microfluidic immune profiling reveals severe immune response signatures”, published recently in Small, a weekly peer-reviewed scientific journal covering nanotechnology, and included a pilot study of 85 donors recruited from the National University Hospital (NUH) emergency department. The paper was led by Dr Kerwin Kwek Zeming, senior postdoctoral associate at SMART CAMP, and co-authored by Professor Jongyoon Han, Principal Investigator at SMART CAMP and Professor of Biological Engineering and Electrical Engineering at MIT, and Dr Win Sen Kuan, Research Director, Emergency Medicine Department, NUH.

The assay focuses on profiling rapidly changing host inflammatory responses, which in a hyper-aggressive state, can lead to sepsis and death. It functions as a sensitive and quantitative assay for immune cell biophysical signatures in relation to real-time activation levels of white blood cells. This new assay is able to detect this immune response within 15 minutes using only 20 microlitres of unprocessed blood through an unconventional L and inverse-L shape pillars of DLD microfluidic technology.

Lead author Dr Kerwin Kwek said, “Our new DLD assay will help address an unmet need in the ER and ICU by significantly reducing waiting time for accurate patient assay results. This could lead to more effective triage decision-making and more appropriate and timely treatment, which are critical to saving lives. More generally, this ground-breaking technology provides new insights into both the engineering of precision microfluidics and clinical research.”

Professor Jongyoon Han added, “In the wake of lessons learnt in emergency rooms in hospitals across the world especially during the COVID-19 pandemic, where medical professionals have been faced with making difficult and at times life-or-death decisions in triage, this new technology represents a hugely exciting and significant breakthrough. By reducing the time taken for assay results from hours to a matter of minutes, SMART CAMP’s new assay could help save lives as we continue to combat the scourge of pathogens and infectious diseases. The assay will also have wider applications, giving clinicians a new and more effective tool in the ER and ICU.”

The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) programme. [APBN]