NTU Singapore scientists build chip to analyse health of white blood cells
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WBC Health Analysis Chip developed by NTU Singapore Scientists.

Researchers from Singapore Nanyang Technological University(NTU Singapore) have now developed a lab-on-a-chip system which helps in identifying the health aspects of an individual’s immune system from a drop of their blood, just within minutes.

Using a combination of microfluidics, i.e, the tiny microscopic channels which can isolate WBCs from blood, and electrical sensors, the new lab-on-a-chip system was able to detect differences in the electrical properties of WBCs taken from healthy individuals and diabetic patients.

The proof of concept device may one day help our doctors to quickly gain insight into an individual’s immune system, and also to spot early signs of inflammation as well as infections that could signal the need for further in-depth tests.

This lab-on-a-chip system is designed and built by Hou Han Wei, Assistant Professor, and Holden Li from the School of Mechanical and Aerospace Engineering. This invention, if successful in the further laboratory and also in clinical assessments, could be turned into a portable lab-on-a-chip system device suitable for family clinics and polyclinics.

The prototype device and its engineering principles were reported in two peer-reviewed journals: Lab on a Chip earlier this year and also in Biosensors and Bioelectronics in October last year.

As our immune health is often implicated in cardiovascular diseases, the researchers say that their lab on a chip device can potentially be an additional screening tool for doctors in order to use for early detection of cardiac diseases. In Singapore, cardiovascular diseases accounted for about 30.1 percent of all deaths in the year 2017 while diabetes is a serious health problem which affects about ten percent of the world’s population.

How this invention works

Asst Prof Hou, the faculty member at the Lee Kong Chian School of Medicine at NTU, said that their lab-on-a-chip device detects electrical differences between a healthy WBC and an unhealthy one. Abnormal WBCs have been reported as an early biomarker for increased risk of cardiovascular diseases and it also suggests an ongoing inflammation.

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Using very tiny channels, the lab-on-a-chip first physically separates the various blood cells by size into the different outlets, just like a coin-sorting machine. The isolated WBCs are then run through a special channel where the electrical impedance is measured for each cell at very high speed (100s of cells per second).

Electrical impedance of an abnormal cell is usually higher when compared to that of the impedance of a healthy cell. The abnormal cell is larger in size and has different membrane properties.

WBCs form a significant part of the body’s immune system. And neutrophils are the first line of defense when infection or inflammation strikes the body.

Asst Prof Hou said that their chips can isolate thousands of WBCs from a single drop of blood and, within minutes. It can tell if these cells are electrically different from normal, which would be an indicator of a health issue that has to be further investigated by doctors.

He further added that more importantly, their process also does not use any chemical biomarkers or antibodies, that makes this assay a very cheap, easy to use, and that it can do further analysis on the same WBCs which have already run through the chip.

Lab-on-a-chip’s possible use in clinical testing

Asst Prof Holden Li said that the material used in making new lab-on-a-chip is a common medical-grade polymer. And this chip is easily manufactured using existing machinery and can be made into a desktop-sized machine for use in clinics.

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He added that their WBC Health Analysis Chip was designed for easy scale-up by the companies, with an integrated system built from electronic components available on the market currently. The team is looking to commercialize this technology with an industry partner, as they see that there are market demands for a point-of-care device for doctors. This as laboratory equipment, can be used for the study of neutrophils and drug screening, Prof Li added.

The researchers added that the team is also doing more researches on the various electrical impedance levels as well as what each of them signifies, so as to build a sort of reference library for automated analysis, and the team will be also working with doctors to test their prototype in the clinical setting.

Professor Bernhard Boehm, Professor of Diabetes Research at NTU’s Lee Kong Chian School of Medicine, while giving an independent opinion on the research, said that many diabetic patients are also susceptible to chronic infections due to disease affecting the performance of their immune system.

He said that there are a number of limitations to using conventional diagnostic markers for patients with clinical suspicion of infection. In addition to this, there is a need to improve the early diagnosis of bacterial infections and to provide guidance for antibiotic therapy.

A test system which can rapidly guide decisions about the initiation of specific therapies would be of great help in a clinical setting. And this will need in the near future randomized controlled clinical trials to provide the formal proofs that this lab-on-a-chip novel test system is superior to all the currently used conventional diagnostic procedures, added Prof Boehm, who was not part of this research study. This new WBC Health Analysis Chip developed by NTU Singapore Scientists could also be very useful for the study of NETosis which is a newly discovered defense mechanism in the field of immunology.

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During the NETosis defense mechanism, neutrophils cells spit out DNA strands that trap bacterias and viruses, just like a spider’s web, to impede their movements and also to kill these trapped pathogens. However, too much NETosis mechanism also slows down wound healing in diabetes.

NETosis mechanism expert, Assistant Professor Christine Wong, from NTU’s Lee Kong Chian School of Medicine who was not involved in this research study, said that the most widely adopted methodology for studying NETosis propensity currently is real-time imaging or the microscopy of fixed neutrophils.

However, it is a laborious process for scientists to isolate the neutrophils cells for microscopy without affecting their native baseline state, & not influence experimental results.

This new device by Asst Prof Hou and Asst Prof Li may enable rapid and non-biased NETosis mechanism experiments and also quantification, which will be especially useful for drug screening ex vivo, said, Asst Prof Wong, in her independent comment.

He added that if the device can be modified to measure NETosis mechanisms in mouse neutrophils, this would be delightful news for scientists using mouse models, as low neutrophil cell yield is a common obstacle in mouse neutrophil isolation due to their smaller blood volume available and their lower myeloid cell ratio when compared to that of humans.

Asst Prof Wong said that while the new lab-on-a-chip device is unlikely to replace microscopic experiments, in particular when visualization of cell components during the NETosis mechanism is the subject matter, the resources saved from NET quantification can be diverted to those investigations.

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Ria Roy completed her Post Grad degree at the Visvesvaraya Technological University. She has a great grounding in the skills, including technical, analytical and research skills. She is a motivated life science professional with experience of working in famous research institutes