An electrochemical sensor integrated lab-on-a-CD system for phenylketonuria diagnostics.

Area of Science:

• Biomedical Engineering
• Analytical Chemistry
• Clinical Diagnostics

Background:

• Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene.
• Elevated blood phenylalanine (Phe) levels due to impaired PAH enzyme activity can lead to severe neurological damage, including psychomotor retardation.
• Early diagnosis and continuous monitoring of Phe levels are critical for effective PKU management and preventing long-term complications.

Purpose of the Study:

• To develop and validate an automated lab-on-a-CD system for the early diagnosis and treatment monitoring of PKU.
• To create a portable, sensitive, and reliable device for rapid quantification of phenylalanine in whole blood samples.
• To compare the performance of the developed system with the established gold standard High-Performance Liquid Chromatography (HPLC) method.

Main Methods:

• A miniaturized lab-on-a-CD system integrating disposable cartridges, a mini centrifuge, and an electrochemical sensing unit was designed.
• Disposable cartridges featured modified screen-printed gold electrodes with electrochemically reduced graphene oxide for enhanced sensitivity.
• Amperometric detection was employed, utilizing phenylalanine dehydrogenase to oxidize Phe and NAD+ to NADH, with measurements performed within a 0-20 mg dL⁻¹ range.

Main Results:

• The lab-on-a-CD system demonstrated a 1.5-fold increase in measurement sensitivity due to graphene oxide modification.
• Key performance metrics included a limit of detection (LOD) of 0.0524 mg dL⁻¹, limit of quantification (LOQ) of 0.1587 mg dL⁻¹, and a sensitivity of 0.3338 μA mg⁻¹ dL.
• The system achieved an accuracy of 84.1%, closely comparable to the HPLC gold standard (83.1%), with results obtained in under 20 minutes.

Conclusions:

• A portable, automated lab-on-a-CD device for rapid, accurate, and highly sensitive phenylalanine detection in whole blood has been successfully developed.
• This system provides a promising solution for early PKU diagnosis and continuous monitoring of treatment efficacy.
• The developed technology offers a viable alternative to conventional methods, potentially improving patient outcomes through timely intervention and management.