A new label-free immune profiling assay has been developed by researchers from the Critical Analytics for Manufacturing  Personalized Medicine (CAMP), an interdisciplinary research group within the Singapore-MIT Alliance for Research and Technology (SMART), to better profile aggressive, rapidly changing host immune response in cases of infection, for example COVID-19.

In cases of acute infection, the status of a patient’s immune response can often be volatile and will likely change within minutes. This has been attributed to the now well-studied phenomenon of cytokine storms, which precipitate the rapid release of immune cells and inflammatory molecules and are brought on by a hyper-aggressive host immune response.

For severe COVID-19, infection often results in a dysregulated immune response and eventual death via sepsis. CurrentCOVID-19 risk stratification methods, based on age and comorbidity, remain a significant challenge and can be inaccurate, thus leading to inefficient deployment of resources in healthcare settings.

Hence, there exists a pressing need for assays that are able to rapidly and accurately inform on the state of the immune system, especially 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 additionally ensures timely intervention in the emergency department (ED) and prevents unnecessary admission to the intensive care unit (ICU).

Thankfully, the new assay developed by SMART researchers focuses on quantifying and profiling immune states of white blood cells (WBCs) instead of existing and labour-intensive methods that focus on detecting pathogens themselves. The assay needsonly a small amount of blood to be processed with unconventional L and inverse-L shaped pillars of deterministic lateral displacement (DLD) microfluidic technology – the assay can sensitively measure real-time activation of WBCs in response to various internal or external triggers, which in turn reflect a patient’s current immune response state.

In short, the assay is able to accurately and quickly assess patients’ immune response states by profiling immune cell size, deformability, distribution, and cell counts; and provides considerable advantages over existing methods of profiling the immune system and its activity, including measuring blood serum cytokine profile(s).

Dr. Kerwin Kwek Zeming, Senior postdoctoral associate at SMART CAMP, 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.”

There is also considerable potential for the new SMART assay to be developed into a portable unit that can perform point-of-care blood-sparing assays which could significantly improve the diagnosis and differentiation of patients in the ER and other primary or critical care settings. This application will enable clinicians to be able to quickly identify at-risk patients and take immediate action to mitigate or prevent organ dysfunction and other adverse effects of a hyper-aggressive immune response.

“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,” added Professor Jongyoon Han, Principal Investigator at SMART CAMP and Professor of Biological Engineering and Electrical Engineering at MIT.

“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,” Professor Han said.

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