New nanotech test will save hundreds of patients with critical shock

With a drop of blood and a test based on nanostructures, doctors will be able to provide rapid and life-saving treatment for seriously ill patients in a few years. The test is being developed in collaboration between Rigshospitalet and the Technical University of Denmark, DTU.

A shot of adrenaline is standard treatment when a patient is in critical shock due to trauma, sepsis or cardiac arrest. But for hundreds of patients a year, this turns out to be the wrong treatment because they already have critically high levels of adrenaline in their blood, sending their heart into overdrive and increasing their risk of death.

A new rapid test from a group of researchers at DTU will be able to show doctors whether the patient needs adrenaline or another form of treatment to survive, typically beta blockers, which block the action of adrenaline, thus lowering the heart rate and reducing the amount of blood the heart pumps out every minute.

The new test is being developed in collaboration with professor in transfusion medicine Pär Johansson from Rigshospitalet. He has found that if you measure the content of so-called succinic acid in the blood and use it as a biomarker, it can show doctors which patients have a more severe reaction to shock and release particularly high levels of adrenaline into the blood. Professor Winnie E. Svendsen from DTU Bioengineering has utilized this knowledge in her work to develop the new rapid test.

Biomarker and the state of shock

Succinic acid

Succinic acid, also known as succinate, is a substance known as a metabolite, a product produced by cells in the body's energy production. A high level of adrenaline in the blood can indirectly lead to an increase in succinic acid. Adrenaline increases the body's metabolism and energy production, which can lead to increased production of metabolites such as succinic acid. This happens especially during stressful situations where the body needs more energy.

Shock

In the medical world, shock is a term used to describe a condition where the body's organs do not receive enough oxygenated blood to function normally. The condition is life-threatening and requires rapid treatment during hospitalization.

The delivery of oxygen to the body depends on several factors, and shock can occur when:

• The heart fails and is unable to pump blood and oxygen around the body in sufficient quantities.
• The blood contains too few red blood cells due to blood loss, if there is too little fluid in the bloodstream due to fluid and/or blood loss.
• Blood vessels dilate, and blood pressure drops as a result of a severe infection—also known as septicemia, where bacteria release toxic substances into the bloodstream.

Common causes of shock are therefore heart disease, major hemorrhages, major burns, severe infections leading to sepsis, severe vomiting or a thin stomach.

The test measures electrolytes from succinic acid

On Svendsen's workbench are 20 of the electronic circuits that each of the new tests will include. The circuits are shaped like small chips in which the researchers have used a laser to burn a track in a polyimide film, which is a special type of plastic with very high strength and is used in both spacecraft and small electronic devices.

The laser-fired track creates an electrically conductive pattern of carbon graphene, which has free electrons that can move through the lattice and conduct electricity. By applying a patented layer of nanostructures to the pattern, the burnt pattern can release electrolytes from the succinic acid in the blood sample, creating a current that can be measured and read. This gives the doctor an answer that can determine what treatment the patient should receive.

Results ready in 10 seconds

The specialty of the test lies in the layers applied to the electronic circuit that react to succinic acid. The layers are nano-sized, larger than single atoms, but still very small compared to particles we can see with the naked eye.

The nanostructures have the quality of expanding the sensor surface in the test because the blood droplet doesn't just slide across a flat surface, but is instead sent up and down a much larger surface of nanostructures that rise vertically on the sensor surface. This is how doctors can get the crucial answer so quickly. Otherwise, the test could not be used on critically ill patients who are balancing between life and death in crucial minutes.

In addition, a test based on nanostructures is more robust than other types of sensors, such as those based on enzymes, which was the researchers' original idea for a rapid test.

Enzymes are more sensitive to work with because they need to be applied as an extra layer on the chip and are therefore more time-consuming to produce.

"The best results occur when the blood sample encounters a molecule that can act as a chemical catalyst to release the electrolytes from the organic succinic acid. That's why we were so excited when we succeeded in getting succinic acid to react with the nanostructures," says Svendsen.

The goal is for the test to deliver an answer within 10 seconds. The research group at DTU will spend the next two years designing the test kit, which will consist of a chip on which a patient's blood drop is dripped and a reader that the doctor inserts the chip into and reads a number. The researchers are also testing a solution where the test result is transmitted from the reader via Bluetooth so that the result can be viewed on a mobile phone.

Once the test has been validated and approved for a clinical trial, it will be tested in a trial with 200 patients at Herlev, Bispebjerg and Nordsjællands Hospitals who will be randomized to receive either beta blockers or placebo.

Provided by Technical University of Denmark