Rapid diagnosis of sepsis
Sepsis occurs as a result of the body's immune response to infection, which triggers massive inflammation, causing palpitations, high fever, shortness of breath and other changes. If you do not start timely treatment, an excessive inflammatory reaction can lead to septic shock, in which blood pressure drops, multiple organ failure develops. To diagnose sepsis, doctors traditionally rely on various tools, including vital signs, blood tests, imaging methods, and other laboratory tests.
Recently, researchers have discovered biomarker proteins in the blood, which are early signs of sepsis. One promising biomarker is interleukin-6 (IL-6), produced in response to inflammation. In patients with sepsis, IL-6 levels may rise several hours before other symptoms appear. But even at such elevated levels, the concentration of this protein in the blood is too small for traditional analytical devices to detect it quickly.
In an article presented at the conference "Engineering in Medicine and Biology", researchers from the Massachusetts Institute of Technology describe a microfluidics-based system that automatically determines clinically significant levels of IL-6 for the diagnosis of sepsis within 25 minutes.
In one microfluidic channel, microbeads with antibodies are mixed with a blood sample and capture the IL-6 biomarker. In the other channel, the beads containing the biomarker stick to the electrode. The voltage applied through the electrode generates an electrical signal in each ball with a biomarker, which is then converted into information about the concentration level of the biomarker.
Integrated automated design
Traditional analyzers that detect protein biomarkers are bulky, expensive devices that require about a milliliter of blood and give results within a few hours. Portable systems have been developed in recent years, microliters of blood and about 30 minutes of time are enough to obtain similar results.
But such laboratory systems can be very expensive because they contain optical components for detecting biomarkers. They also capture only a small amount of proteins, many of which are among the most common in the blood. Any attempts to reduce the cost, reduce the number of components or increase the number of proteins negatively affect their sensitivity.
In their work, the researchers wanted to reduce the analysis components based on magnetic beads, which are often used in laboratories placed in an automatic microfluidic device, the area of which is several square centimeters.
The beads are coated with an antibody that captures IL-6, as well as a catalyzing enzyme. The beads and the blood sample are injected into the device, falling into the "analysis zone", which is a loop. Along the circuit is a peristaltic pump, usually used for fluid control, with valves automatically controlled by an external circuit. Opening and closing the valves in a certain order promotes blood and mixing balls. After about 10 minutes, IL-6 proteins bind to antibodies on the granules.
The automatic readjustment of the valves at this time propels the mixture into a smaller loop called the "detection zone". A tiny magnet collects the balls and then sends them around the loop. After about 10 minutes, the beads stick to an electrode coated with an antibody that attracts IL-6. At this time, the solution enters the loop and washes out the empty balls, and the balls with the IL-6 protein remain on the electrode.
When voltage is applied to the solution, each remaining ball generates a small amount of electricity. The amperometry method converts this current into a readable signal. The device counts the signals and calculates the concentration of IL-6.
The doctor's task is to place a blood sample with a pipette, press the button and after 25 minutes get information about the concentration of IL-6.
Five microliters of blood is enough for the device, which is about a quarter of the volume of blood usually taken from a finger. The device records the concentration of IL-6 up to 16 picograms per milliliter, which is lower than the concentrations indicating sepsis, which means that the device is sensitive enough to detect a clinically significant concentration.
Promising opportunities
The device has eight separate microfluidic channels for simultaneous measurement of as many different biomarkers or blood samples as possible. In separate channels, different antibodies and enzymes can be used to detect different biomarkers, or different antibodies in the same channel can be used to detect multiple biomarkers simultaneously.
The researchers plan to create a device for a complex of important biomarkers of sepsis, including interleukin-6, interleukin-8, C-reactive protein and procalcitonin. But there is really no limit to how many different biomarkers a device can measure for any disease, since the platform allows you to increase the physical area of the device and design more channels to detect as many biomarkers as needed.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on MIT materials: Microfluidics device helps diagnose sepsis in minutes.