In alternative embodiments are provided methods, devices and systems that use clinical data to determine whether bilirubin binding is normal in a newborn infant with hyperbilirubinemia in order to detect in vivo neurologically toxic levels of bilirubin and to determine whether treatment is needed to prevent a bilirubin-induced neurological injury (e.g. encephalopathy). In alternative embodiments, also provided are devices and systems comprising automated micro-fluid handling technologies such as zone fluidics systems to obtain a bilirubin binding panel. In alternative embodiments, also provided are methods for using the bilirubin binding panel to determine if treatments are needed to ameliorate, reverse, or prevent a bilirubin-induced neurological injury (e.g. encephalopathy) in an individual in need thereof such as a newborn with hyperbilirubinemia (jaundice), and for commencing the treatment, if needed.