Disclosed are systems and methods for selecting
biological particles (e.g., cells or nuclei) based on specific binding to a substrate and single-biological particle measurement of analytes from the substrate-bound
biological particles (e.g., cells or nuclei). Single
biological particles (e.g., cells or nuclei) from a
population of biological particles are captured through their binding to biological particle-(e.g.,
cell- or
nucleus-) and / or molecule-specific biological particle (e.g.,
cell or
nucleus) capture moieties on a substrate. Analytes are released from the single captured biological particles (e.g., cells or nuclei) and bind to
analyte-specific
barcode molecules associated with the specific biological particle (e.g.,
cell or
nucleus) capture moieties to which a biological particle (e.g., a cell or nucleus) has bound. Analysis of the
barcode molecules identifies the bound analytes. The systems and methods are used to select and capture immune cells, such as T-cells that bind specific
peptide epitopes through their T-cell receptors (TCRs) or B-cells that bind
antigen through their
B cell receptors (BCRs). Detection and analysis of
barcode molecules that have bound cellular analytes comprising rearranged V(D)J-expressing RNAs from the T-cells or B-cells allows identification of the specific TCR sequences that recognize and bind the specific
peptide epitopes or specific BCR sequences that recognize and bind specific antigens.