Researchers develop point-of-care device to aid monitoring of inherited and hepatic metabolic disorders

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Ammonium is a biomarker used to diagnose a series of rare inherited metabolic disorders, such as primary urea cycle disorders and different organic acidemias, as well as other metabolic and environmental conditions affecting liver function, which can lead to a secondary dysfunction of the urea cycle. Ammonium is also useful in the study and monitoring of different hepatopathies (diseases affecting the normal functioning of the liver) caused by the consumption of alcohol or other drugs, medications and other environmental factors.

In all these disorders, an excess of ammonium is produced, putting the patient’s health at risk. Values ​​exceeding 200 micromoles per liter of blood are considered severe cases of hyperammonemia (high concentration of ammonium in the blood) which can cause irreversible brain damage, and can even lead to death, if values ​​exceed 500 micromoles per litre. Therefore, real-time early diagnosis is crucial to minimize the impact of an episode of hyperammonemia on neurological functions. Currently, patients diagnosed with disorders that include episodes of hyperammonemia must be periodically visited in hospital, where a blood sample is taken, which must then be processed and analyzed in the laboratory.

Researchers from the Sensors and Biosensors (GSB) research group of the Department of Chemistry of the UAB, in collaboration with the Hospital Sant Joan de Déu and the UPC, have developed a point-of-care (POC) analyzer that monitors the level of ammonium in the patient’s blood using a decentralized method at the point of care, instead of sending blood samples to be analyzed in hospital laboratories, where traditional equipment is used. The new device aims to decentralize the determination of ammonium in the blood, making the analysis possible in small health centers with direct blood measurements and no need for previous treatments. This would mean multiplying the number of monitoring sites, simplifying the process and reducing the time needed to make medical decisions.

Increasing the frequency of blood tests to determine ammonium levels is vitally important.”


Mar Puyol, study director, UAB researcher

She goes on to say that: “Reduction of excess ammonium in a patient with hyperammonemia is done by restricting protein intake, using drugs to enhance ammonium removal, and dialysis and hemofiltration in the most acute cases, so that the patient’s evolution will be all the more favorable the quicker the doctors act, and this can be achieved by using point-of-care analyzers such as the one we have developed “.

Hospital validation

The research team is preparing a prototype that will work in semi-autonomous conditions. Once the device is ready, it will measure all the ammonium samples analyzed every day at Sant Joan de Déu Hospital with the conventional method and with the new equipment created by the researchers. Nevertheless, Puyol warns that “hundreds of samples will be required before the final prototype of the point-of-care analyzer is validated. The next step will then be the industrialization of the device to launch it on the market. There are still several steps to reach this scenario, but it is expected that the device will become a cost-effective alternative that can also facilitate liver disease surveillance in developing countries.”

Device Operation

The device uses a microfluidic platform that includes a potentiometric detection system and a gas separation membrane. In this way, it is possible to automatically separate the ammonium in the form of ammonia from the rest of the complex matrix of the blood, obtaining a selective detection free from any other type of interference. This guarantees a precise and exact determination of the ammonium concentration in whole blood and not in plasma, which is the classical method used to analyze this parameter.

The study, led by researchers Julián Alonso-Chamarro and Mar Puyol Bosch, from the Sensors and Biosensors Research Group of the UAB Department of Chemistry, is the result of an R&D&I Proof of Concept project (PDC2021- 121558-I00), carried out in collaboration with researchers Rafael Artuch from the Sant Joan de Déu Hospital (HSJD) and Javier Rosell from the Center for Research in Biomedical Engineering (CREB) of the UPC. This study includes the support and involvement of Fundación PKU-OTM (phenylketonuria and other inherited metabolic disorders). The validation of the system is carried out at the Hospital Sant Joan de Déu in Barcelona.

Source:

Autonomous University of Barcelona

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