Researchers are developing point-of-care device to facilitate monitoring of hereditary and hepatic metabolic disorders

Researchers are developing point-of-care device to facilitate monitoring of hereditary and hepatic metabolic disorders

Ammonium is a biomarker used to diagnose a number of rare inherited metabolic disorders such as urea cycle. Ammonium is also useful in studying and monitoring various hepatopathies (diseases that affect the normal functioning of the liver) caused by the consumption of alcohol or other drugs, medications and other environmental factors.

In all of these diseases, an excess of ammonium is produced, which endangers the patient's health. Levels above 200 micromoles per liter of blood are considered severe cases of hyperammonemia (high concentration of ammonium in the blood), which can cause irreversible damage to the brain and even lead to death if levels exceed 500 micromoles per liter. Therefore, early, real-time 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 regularly taken to the hospital, where a blood sample is taken, which then needs to be treated and analyzed in the laboratory.

Researchers from the Sensors and Biosensors (GSB) research group of the Department of Chemistry at UAB, in collaboration with the Sant Joan de Déu Hospital 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 for analysis to hospital laboratories where traditional equipment is used. The new device aims to decentralize blood ammonium determination and enable analysis in smaller health centers with direct blood measurements and without prior treatment. This would mean multiplying the number of monitoring sites, simplifying the process and reducing the time required for medical decisions.

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

Mar Puyol, principal investigator, UAB researcher

She continues: “Reducing the excess of ammonium in a patient with hyperammonemia is carried out by restricting protein intake, using drugs to improve ammonium excretion and dialysis and hemofiltration in the most acute cases, so that the patient's development progresses the more favorably the faster the doctors act, and this can be achieved through the use of point-of-care analyzers such as the one we have developed.”

Validation in the hospital

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The research team is preparing a prototype that will function semi-autonomously. Once finished, the device will measure all the ammonium samples analyzed daily at the Sant Joan de Déu Hospital using the traditional method and with the new equipment developed by 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 stage will then be the industrialization of the device in order to bring it to market. There are still a few phases to reach this scenario, but it is expected that the device will become an economical alternative that can facilitate the monitoring of liver diseases also in developing countries."

How the device works

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 blood matrix, achieving a selective detection free from any other types of interference. This guarantees an accurate and precise determination of the ammonium concentration in whole blood and not in plasma, which is the traditional method for analyzing this parameter.

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

Source:

Autonomous University of Barcelona

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