A method of estimating a number of nucleotide incorporations when sequencing a polynucleotide strand, comprising: flowing a series of nucleotide flows onto a reactor array comprising a plurality of chemical field-effect transistors and having multiple reaction confinement regions, one or more copies of the polynucleotide strand being located in a loaded reaction confinement region of the reactor array; receiving output signals from the reactor array; determining a background signal for the loaded reaction confinement region using a model of an output signal from the loaded reaction confinement region; determining an incorporation signal from the loaded reaction confinement region using the model of an output signal from the loaded reaction confinement region; wherein the model comprises a function for a background signal component and a function for an incorporation signal component, wherein the step of determining the background signal comprises fitting the model to background signal data from the loaded reaction confinement region, wherein the function for the background signal component comprises an output signal from a representative empty reaction confinement region, wherein the function for the background signal component comprises a rate parameter relating to a rate of change in the amount of hydrogen ions in the loaded reaction confinement region, wherein the function for the background signal component further comprises a ratio parameter relating to a ratio of a rate of change in the amount of hydrogen ions in a representative empty reaction confinement region relative to the rate of change in the amount of hydrogen ions in the loaded reaction confinement region, the method further comprising: determining an estimate of a number of nucleotides incorporated into the polynucleotide strand, wherein the step of determining an estimate of the number of nucleotides incorporated further comprises at least one of fitting the incorporation signal model to the incorporation signal and comparing the incorporation signal to a set of reference incorporation signal curves. receiving output signals from the reactor array; determining a background signal for the loaded reaction confinement region using a model of an output signal from the loaded reaction confinement region; determining an incorporation signal from the loaded reaction confinement region using the model of an output signal from the loaded reaction confinement region; wherein the model comprises a function for a background signal component and a function for an incorporation signal component, wherein the step of determining the background signal comprises fitting the model to background signal data from the loaded reaction confinement region, wherein the function for the background signal component comprises an output signal from a representative empty reaction confinement region, wherein the function for the background signal component comprises a rate parameter relating to a rate of change in the amount of hydrogen ions in the loaded reaction confinement region, wherein the function for the background signal component further comprises a ratio parameter relating to a ratio of a rate of change in the amount of hydrogen ions in a representative empty reaction confinement region relative to the rate of change in the amount of hydrogen ions in the loaded reaction confinement region, the method further comprising: determining an estimate of a number of nucleotides incorporated into the polynucleotide strand, wherein the step of determining an estimate of the number of nucleotides incorporated further comprises at least one of fitting the incorporation signal model to the incorporation signal and comparing the incorporation signal to a set of reference incorporation signal curves. determining an estimate of a number of nucleotides incorporated into the polynucleotide strand, wherein the step of determining an estimate of the number of nucleotides incorporated further comprises at least one of fitting the incorporation signal model to the incorporation signal and comparing the incorporation signal to a set of reference incorporation signal curves.