title: Copper nanowires immobilized on the boards of microfluidic chips for the rapid and simultaneous diagnosis of galactosemia diseases in newborn urine samples.
abstract: Galactosemia is a rare disease that is diagnosed through the identification of different metabolite profiles. Therefore, the specific detection of galactose 1-phosphate (Gal 1-P), galactose (Gal), and uridyl diphosphate galactose (UDP-Gal) confirms type I, II, and III galactosemia diseases. Because of the low prevalence of galactosemia, sample availability is very scarce and screening methods to diagnose the illness are not commonly employed around the world. This work describes the coupling of microfluidic chips (MCs) to copper nanowires (CuNWs) as electrochemical detectors for the fast diagnosis of galactosemia in precious newborn urine samples. Conceptually speaking, we hypothesize that the inherent selectivity and sensitivity of CuNWs, toward galactosemia metabolites detection in connection with MC selectivity could allow the fast and simultaneous detection of the three galactosemia biomarkers, which implies the fast diagnosis of any galactosemia type in just one single analysis. Electrosynthesized CuNWs show a well-defined shape, with an average length of 6 μm and a width of 300 nm. The modified electrodes exhibited an enhanced electroactive surface area twice as high as the nonmodified ones. Very good intraelectrode repeatability with relative standard deviations (RSDs) of <8% (n = 10) and interelectrode reproducibility with RSDs of <12% (n = 5) were obtained, indicating an excellent stability of the nanoscaled electrochemical detector. Under optimum chemical (3 mM NaOH, pH 11.5), electrokinetic (separation voltage +750 V, injection +1500 V for 5 s) and electrochemical (E = +0.70 V in 3 mM NaOH, pH 11.5) conditions, galactosemia diseases were unequivocally identified, differentiating between type I, II, and III, using selected precious ill diagnosed newborn urine samples. Detection proceeded within less than 350 s, required negligible urine sample consumption, and displayed impressive signal-to-noise characteristics (ranging from 14 to 80) and micromolar limits of detection (LODs) much lower than the cutoff levels (Gal 1-P > 0.4 mM and Gal > 1.4 mM). Excellent reproducible recoveries (93%-107%, RSDs <6%) were also achieved, revealing the reliability of the approach. The significance of the newborn urine samples studied confirms the analytical potency of MC-CuNWs approach, enhancing the maturity of the microchip technology and opening new avenues for future implementation of screening applications in the field.
authors.affiliation: Department of Analytical Chemistry, Physical Chemistry and Chemical Engineering, University of Alcalá , E-28871, Alcalá de Henares, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: García
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Alonso-Fernández
authors.forename: Alberto
authors.initials: A
authors.lastname: Escarpa
mesh_terms: D015415:Biomarkers / Q000652:urine; D003300:Copper / Q000737:chemistry*; D055664:Electrochemical Techniques / Q000295:instrumentation; D004566:Electrodes; D005693:Galactosemias / Q000175:diagnosis* / Q000652:urine*; D006801:Humans; D007231:Infant, Newborn; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D053770:Nanowires / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003300:Copper