US scientists have developed a simple electrochemical device that can be used to diagnose liver disease.

Liver disease affects more than 170 million people worldwide. One way to identify the disease is to look for increased bile acid concentration in the blood. Existing bile acid tests require expensive, non-portable equipment, which is a significant problem for the many sufferers who live far from medical facilities, says Brandon Bartling, at Case Western Reserve University, Cleveland: 'Doctors are willing to travel far and wide but they can't carry their testing facilities with them in their bag.'

Now Bartling and colleagues have made a bile acid sensor that is portable and cheap. It consists of an oxidising enzyme and its co-enzyme, nicotinamide adenine dinucleotide (NAD⁺), immobilised on an electrode's surface. When Bartling dropped a bile acid sample on to the sensor, the enzyme oxidised the acids, producing the reduced form of the co-enzyme, NADH, as the by-product. The sensor then oxidised the NADH, generating a current proportional to the bile acid concentration. Bartling showed that the sensor could detect the total bile acid concentration in calf serum samples containing mixtures of the three principal human bile acids. He says this suggests that accurate diagnosis using human samples could be possible.

The sensor operates at a lower potential than similar biosensors, says Bartling, meaning that it oxidises only NADH and not any other species present in the sample. As a result, it doesn't need size-exclusion membranes, which are used by other biosensors to filter out other oxidisable species that might interfere with current measurement.

Membranes increase the sensor's complexity and their pores can get blocked with chemicals, like dust clogging an air filter, explains Bartling. Product then builds up on the electrodes, reducing their sensitivity. 'Using a sensor without a membrane gives molecules greater freedom to move away from the electrode's surface,' he adds.

Chong Yuan, managing director of Diazyme Laboratories, La Jolla, US, which makes diagnostic tests, comments that the results may also have 'wide application potential for various clinically relevant biomarkers that can be involved in the enzymatic formation of NADH, such as homocysteine, a new emerging cardiovascular risk factor, and alpha-methylacyl-CoA racemase, a new and more specific prostate cancer marker'. But he warns that 'further studies are needed to validate the test with human samples'.

Bartling is focusing on liver disease for the moment. He says he plans to develop a series of affordable, portable and user-friendly sensors to test for other biomarkers that can help to discriminate the type and severity of liver disease.

Frances Galvin

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