SMART develops a fast definitive lateral motion assay to assess immune response

• The state-of-the-art labeled assay uses noninvasive L-shaped columns and internal microfluidic lateral separation (DLD) technology to measure and account for white blood cell immune states (WBCs) with assessing biochemical properties of size, deformation, dispersion, and cell. count
• The assay requires only 20 microlitres (μl) of unprocessed blood and will take just 15 minutes – much faster than existing methods that require up to 15 milliliters (ml) of blood and will take co -at least a few hours to produce results
• This new technology measures and reports the host’s often volatile immune response, resulting in a more accurate assessment of patients ’pathophysiology.
• Routine methods for early diagnosis of disease focus on the detection of pathogens with low prevalence, and are time consuming, with low sensitivity, and do not accurately reflect the severity of the disease.

Singapore, 25 March 2021 – Researchers from Critical Analytics for Manufacturing Personalized-Medicine (CAMP), an Interdisciplinary Research Group (IRG) at the Singapore-MIT Federation for Research and Technology (SMART), an MIT research initiative in Singapore, has developed a new initiative. unlabeled immune profiling assay that describes the immune response of a rapidly changing host in the absence of infection, in departure from existing methods aimed at detecting the pathogens themselves , which can often be at low levels within a host. This novel technology offers several advantages over conventional methods, being both much faster, more responsive and more accurate.

The new assay is outlined in a paper titled, “Unlabeled biochemical markers from whole-blood microfluidic immune profile show immune response signatures”, recently published Small, a weekly peer-reviewed scientific journal covering nanotechnology, and includes a pilot study of 85 donors recruited from the emergency department of the National University Hospital (NUH). The paper was led by Dr Kerwin Kwek Zeming, senior postgraduate associate at SMART CAMP, and co-author with Professor Jongyoon Han, Principal Investigator at SMART CAMP and Professor of Biological Engineering and Engineering Electricity at MIT, and Dr. Win Sen Kuan, Director of Research, Department of Emergency Medicine, NUH.

In many cases, the main culprit behind the manifestation of disease, the severity of the disease, and patient mortality is an overly aggressive immune response. For example, as a result of the Spanish pandemic of 1918, there was a very high number of deaths among healthy young adults. This is because cytokine tumors are now well studied, rapidly removing immune cells and inflammatory molecules and triggered by a hyper-invasive immune response. In a more recent example, cases of severe COVID-19 infection often result in death through sepsis and an immune response with dysregulation, while conventional risk-based procedures based on age and comorbidity remain a major challenge and can to be mistaken. In addition, routine testing of Covid-19 does not affect the severity of the immune response and thus can lead to inefficient use of resources in health care settings.

In cases of severe disease, the status of a patient’s immune response can be volatile and can change within minutes. Therefore, there is an urgent need for assessments that are able to provide information quickly and accurately on the state of the immune system. This is especially critical in early testing among patients with infectious disease and prediction of subsequent disease decline. At the same time, this will empower medical staff to make 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).

The new assay developed by SMART researchers will focus on describing the host’s rapidly changing inflammatory response, which may be in a hyper-aggressive state, leading to sepsis and death. A 15-min labeled immune profile assay from 20 μL of unprocessed blood using non-standard L-shaped columns and L-inverse form of DLD microfluidic technology was developed, acting as a sensitive and quantitative assay of bio signatures -cemical cell immunity to real-time WBCn activation levels. As WBCs are activated by a variety of internal or external stimuli, the assay can consciously measure the extent and direction of these changes, which in turn reflects a state of immune response. patient routine. Thus, the new assay developed by SMART researchers is able to accurately and quickly assess patient immune response states by reporting immune cell size, deformability, dispersion, and cell count.

Importantly, the new assay offers significant benefits over the existing methods of accounting for the immune system and its activity. These include leukocyte gene quantification, cell surface biochemical markers, and serum cytokine serum imaging. In particular, these routine procedures require sample dilution or pretreatment measures, as well as labor-intensive, expensive equipment and antibody labeling methods. As a result, these methods usually require a few hours, at a minimum, to return results. This is a major point of pain and disadvantage in triage and the emergency department, where clinicians need to conduct proper clinical assessments as early as possible. The labor-intensive and time-consuming nature of these routine methods severely limits the clinical utility for rapid triage and prevents their wider implementation within the ER or ICU.

In comparison, since this new SMART assay only takes 15 minutes, uses only 20 μL of whole blood, and only requires video capture frame rates of up to 150 fps, there is a huge potential for the technology developed into a portable unit that can. perform point-of-care hemorrhage assessments that may significantly improve patient diagnosis and differentiation in the ER and other primary or emergency care settings. This application will allow clinicians to be able to quickly identify at-risk patients and take immediate action to reduce or prevent organ degeneration and other side effects of a hyper-invasive immune response.

Lead author Dr Kerwin Kwek said, “Our new DLD assay will help address an unmet need in the ER and ICU by significantly reducing the waiting time for accurate patient assessment results. This could lead to more effective triage decisions and more appropriate and timely treatment, which is essential for saving lives. In general, this state-of-the-art technology brings new perspectives to both. part on detailed microfluidics engineering and clinical study. “

Professor Jongyoon Han said, “As a result of lessons learned in emergency rooms in hospitals around the world, especially during the COVID-19 pandemic, where medical professionals face difficult decisions and at times life-or-death in triage, this new technology represents a very interesting and important break. By reducing the time taken for assay results from hours to a few minutes, a new SMART CAMP assay could help save lives while continuing to fight the brutality of pathogens and infectious diseases . they also have broader applications, providing clinicians in the ER and ICU with a new and more efficient tool. “

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The research is conducted by SMART and supported by the National Research Foundation (NRF) Singapore under their Campus for Research Excellence and Technology Enterprise (CREATE) program.

About emergency checkers for personalized-manufacturing (CAMP)

CAMP is a SMART interdisciplinary research group launched in June 2019. It aims to develop better ways to produce living cells as pharmaceuticals, or cell therapies, to enable more patients on promising and approved treatments. The researchers at CAMP address two key bottlenecks facing the production of a range of potential cell therapies: critical quality effects (CQA) and process analysis technologies (PAT). Leveraging deep collaboration within Singapore and MIT in the United States, CAMP designs and demonstrates CQA / PAT capabilities from gas to immune cells. His work treats diseases ranging from cancer to bone loss, targeting persistent and suspended cells, with and without genetic engineering.

CAMP is at the heart of R&D of a broad national effort on cell medicine manufacturing in Singapore.

For more information, visit: https: //camp.elegant.with.edu /

About the Singapore-MIT Alliance for Research and Technology (SMART)

The Singapore-MIT Research and Technology Alliance (SMART) is the MIT Research Initiative in Singapore, established by the Massachusetts Institute of Technology (MIT) in partnership with the Singapore National Research Foundation (NRF) since 2007. SMART is first entity in the Environment for Research Excellence and Technology Enterprise (CREATE) developed by NRF. SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore. SMART is undertaking advanced research projects in areas of interest to both Singapore and MIT. SMART currently comprises an Innovation Center and five Interdisciplinary Research Organizations (IRGs): Antimicrobial Resistance (AMR), Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Disruptive & Sustainable Technologies for Agricultural Precision (DiSTAP), Future Urban Mobility (FM) and Low Energy Electronic Systems (LEES).

SMART research is funded by the National Research Foundation Singapore under the CREATE program.

For more information, visit: http: // smart.with.edu /

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