Researchers at Michigan Institute of Technology have developed a novel sensor that could dramatically speed up the diagnosis of sepsis and save lives by identifying the condition before it is too late.
Credit: Felice Frankel
The small microfluidic sensor can detect a biomarker for sepsis called interleukin-6 (IL-6) in tiny volumes of blood within approximately 25 minutes. The device could provide an inexpensive and more sensitive alternative to current point-of-care systems for the detection of sepsis, which kills nearly 250,000 patients in the U.S every year.
Sepsis requires a fast diagnosis for effective management
Sepsis arises when the immune system triggers a chain of inflammation reactions throughout the body in response to infection. The potentially fatal response causes a high heart rate, severe fever, shortness of breath and can cause septic shock, where blood pressure drops and organs shut down and fail.
To diagnose sepsis, doctors traditionally rely on vital signs, blood tests, and other imaging and lab tests, but diagnosing sepsis in a timely manner so that effective care can be provided remains a challenge.
Traditional assays to detect sepsis biomarkers also often require expensive, bulky machines that require a milliliter of blood and make detection outside of the hospital setting impossible.
In recent years, various point-of-care devices have been developed that can generate results from microliters of blood in around 30 minutes, but these are usually expensive because they mostly use costly optical components to detect the biomarkers.
They also only capture a tiny number of proteins, many of which circulate among the more abundant blood proteins.
Furthermore, any attempts to lower the cost of these devices, the size of their components or to increase the range of proteins that can be detected, reduces their sensitivity.
Interleukin-6 as a biomarker for sepsis
In recent years, researchers have identified blood protein biomarkers that serve as early indictors of sepsis. The blood level of one such biomarker − IL-6 − begins to rise hours before other sepsis symptoms set in, making it a promising candidate for early detection. However, even at these increased levels, the concentration of IL-6 in the blood is too low to be quickly detected by traditional assay devices.
Now, a research paper due to be presented at the Engineering in Medicine and Biology Conference, in Berlin, describes a microfluidics-based system that can detect clinically significant levels of IL-6 in around 25 minutes, using less than a finger prick of blood.
“For an acute disease, such as sepsis, which progresses very rapidly and can be life-threatening, it’s helpful to have a system that rapidly measures these nonabundant biomarkers,” says first author of the research Dan Wu. “You can also frequently monitor the disease as it progresses.”
Miniaturizing a magnetic bead-based assay onto a microfluidics device
In an attempt to design a more affordable alternative to current point-of-care systems, the MIT researchers set out to miniaturize a magnetic bead-based assay onto an automated microfluidics device that is approximately several square centimeters in size.
In one of the device’s microfluidic channels, antibody-laced microbeads mix with blood to capture IL-6 and in another channel, those beads that contain the biomarker attach to an electrode. When voltage is run through the electrode, it generates an electrical signal for each biomarker-laced bead and the signals generated are then translated into a concentration level for the biomarker.
Advantages of the new platform over current systems
Even minute increases in IL-6 can be detected during a test, and if samples need to be processed in parallel, more channels can simply be added to the device. Currently, the design has eight microfluidics channels that can measure as many different biomarkers or blood samples simultaneously.
“This is a very general platform. If you want to increase the device’s physical footprint, you can scale up and design more channels to detect as many biomarkers as you want,” says Wu.
The compact device is inexpensive compared with existing portable systems, easy to use and only requires 5 microliters of blood to test IL-6 levels.
“On their end, doctors just load in a blood sample using a pipette. Then, they press a button and 25 minutes later they know the IL-6 concentration,” adds Wu.
Will we see this technology in the clinic soon?
The technology is not yet ready for clinical use in a hospital setting but plans for refinement are underway. One example includes the ability to detect other sepsis biomarkers, of which there are more than 200 examples that have been approved by the FDA.
If the device is finalized, clinicians may be able to catch sepsis before it is too late and save lives, even in healthcare settings where it would not be practical to use the current platforms.
Matheson, R. Microfluidics device helps diagnose sepsis in minutes. MIT News. July 23, 2019. http://news.mit.edu/