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Blood cells converted into chemical sensors

Chemists have turned red blood cells into long-lived sensors that could be put back into circulation to monitor the makeup of patients’ blood in real time.

Many patients require monitoring of their blood — diabetics, for example, must prick themselves with needles to elicit blood for determining their glucose levels. But extracting blood is both invasive and provides only a one-off measurement. At the American Chemical Society meeting in Philadelphia, Pennsylvania, on Sunday, Xiaole Shao explained how she and her team have built sensors that may one day allow both noninvasive and long-term monitoring of crucial aspects of blood chemistry.

Shao, a chemist at the University of Missouri in Columbia (UM), and her colleagues exploited the fact that near-infrared light will penetrate skin. This means it can trigger fluorescent molecules that are circulating in the blood, and this fluorescence can be picked up by an external monitoring device. If the molecule’s fluorescence changes in response to chemical conditions, these changes can also be detected, and you have a sensor.

But fluorescent dyes can be toxic, and they don’t last long in the body, because they are quickly filtered out. “The solution we found: encapsulate the sensors in red blood cells,” Shao told the meeting. “In this way the sensors can remain in the body and be protected from the immune response.”

To prove the concept, the researchers began with a sensor for pH (how acidic or alkaline something is). They placed red blood cells in a solution that causes them to swell, opening a pore in the cell. If the solution also contains the fluorescent dye, some of this dye will be exchanged with some of the contents of the red blood cell, which can then be resealed. In theory, these sensor–cells could then be injected back into a patient for monitoring, replacing a series of invasive blood samples with a one-time injection.

“When you reseal them [the cells] they really last quite a while in circulation,” says Timothy Glass, an expert on fluorescent sensors at UM, and one of the researchers behind the new sensor. “The expectation is we could keep a sensor in blood for two to three months.”

Anything in the blood that can enter the red blood cell can, in theory, be detected using the right dye. Although this method cannot measure things that do not enter red blood cells — such as calcium — it would work for anything that does, such as glucose, says Glass. Glass says that the researchers have been pleasantly surprised by just how much fluorescence they get from their sensors.

The team now have a grant from the US National Institutes of Health to take the pH sensor work into rats.

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