175 Years of Bilirubin Testing: Ready for Point-of-Care?

Abstract

Bilirubin was first detected in blood in 1847 and since then has become one of the most widely used biomarkers for liver disease. Clinical routine bilirubin testing is performed at the hospital laboratory, and the gold standard colorimetric test is prone to interferences. The absence of a bedside test for bilirubin delays critical clinical decisions for patients with liver disease. This clinical care gap has motivated the development of a new generation of bioengineered point-of-care bilirubin assays. In this Perspective, recently developed bilirubin assays are critically discussed, and their translational potential evaluated.

Keywords: bilirubin; diagnostics; liver disease; point-of-care.

Figure 1

Detection methods of selected investigational bilirubin assays. A) Electrochemistry: an electric current at the electrode surface is induced by direct oxidation of bilirubin or by the hydrogen peroxide generated from the enzymatic oxidation of bilirubin by bilirubin oxidase, and measured by amperometry. B) Fluorescence: the binding of bilirubin to UnaG leads to a fluorescence signal, and bilirubin binding to fluorescent nanoparticles directly or to albumin associated with nanoparticles quenches the fluorescence of the nanomaterials. C) Bioluminescence: bioluminescence resonance energy transfer (BRET) from a luciferase to bilirubin‐binding UnaG results in a spectral shift in bioluminescence. D) Colorimetry: Blood is applied to a filter membrane to isolate plasma, which is subsequently pressed on a paper with a bilirubin sensor. E) Surface‐enhanced Raman spectroscopy (SERS): bilirubin adsorbs to a filter paper containing graphene oxide plasmonic gold nanostar (GO‐GNS) hybrids and induces changes in the SERS spectrum.