An automated biological sample staining system (100, 300), comprising at least one sample substrate holder (202, 302, 806) configured to mount a paraffin-embedded tissue sample; at least one bulk fluid applicator module (116, 306, 400, 420, 500, 520), comprising a bulk fluid applicator needle (404, 424, 426, 524) or slit and a fluid aspirator needle (406, 904, 1004) or slit; the bulk fluid applicator module (116, 306, 400, 420, 500, 520) being configured to maintain a fluid flow between the bulk fluid applicator needle (406, 426) or slit and the fluid aspirator needle (406, 904, 1004) or slit in order to selectively deparaffinize all or a portion of the paraffin-embedded tissue sample; at least one microfluidic reagent applicator (600, 610, 620, 630 710, 800, 1102, 1303) configured to apply a reagent to the sample, the at least one microfluidic reagent applicator (600, 610, 620, 630, 710, 800, 1102, 1303) comprising: a reagent reservoir (612a-d, 622a-d, 632a-d, 804a-d, 902, 1002) and a droplet-on-demand microfluidic actuator (614a, 614b, 614c, 614d, 1404), wherein the reagent reservoir (612a-d, 622a-d, 632a-d, 804a-d, 902, 1002) is fluidically coupled with the droplet-on-demand microfluidic actuator (614a, 614b, 614c, 614d, 1404); at least one relative motion system configured to move one or more of the sample substrate holder(s) (202, 302, 806), the microfluidic reagent applicator(s) (600, 610, 620, 630, 710, 800, 1102, 1303), the bulk fluid applicator module(s) (116, 306, 400, 420, 500, 520), together or separately; and a reagent storage unit (120, 220, 720); a reagent transport system (122, 700) configured to move the exchangeable fluid reagent reservoirs (612a-d, 622a-d, 632a-d, 804a-d, 902, 1002) between the reagent storage unit (120, 220, 720) and the droplet-on-demand microfluidic actuator (614a, 614b, 614c, 614d, 1404), a control system that is programmed to execute at least one staining protocol on the sample, wherein the control system is configured to control the at least one microfluidic reagent applicator (600, 610, 620, 630, 710, 800, 1102, 1303), the at least one bulk fluid applicator module (116, 306, 400, 420, 500, 520), the at least one sample substrate holder (302, 806), the at least one relative motion system, the reagent storage unit (120, 220, 720), the reagent transport system (122, 700) to execute individual steps of the at least one staining protocol. at least one sample substrate holder (202, 302, 806) configured to mount a paraffin-embedded tissue sample; at least one bulk fluid applicator module (116, 306, 400, 420, 500, 520), comprising a bulk fluid applicator needle (404, 424, 426, 524) or slit and a fluid aspirator needle (406, 904, 1004) or slit; a bulk fluid applicator needle (404, 424, 426, 524) or slit and a fluid aspirator needle (406, 904, 1004) or slit; the bulk fluid applicator module (116, 306, 400, 420, 500, 520) being configured to maintain a fluid flow between the bulk fluid applicator needle (406, 426) or slit and the fluid aspirator needle (406, 904, 1004) or slit in order to selectively deparaffinize all or a portion of the paraffin-embedded tissue sample; at least one microfluidic reagent applicator (600, 610, 620, 630 710, 800, 1102, 1303) configured to apply a reagent to the sample, the at least one microfluidic reagent applicator (600, 610, 620, 630, 710, 800, 1102, 1303) comprising: a reagent reservoir (612a-d, 622a-d, 632a-d, 804a-d, 902, 1002) and a droplet-on-demand microfluidic actuator (614a, 614b, 614c, 614d, 1404), wherein the reagent reservoir (612a-d, 622a-d, 632a-d, 804a-d, 902, 1002) is fluidically coupled with the droplet-on-demand microfluidic actuator (614a, 614b, 614c, 614d, 1404); a reagent reservoir (612a-d, 622a-d, 632a-d, 804a-d, 902, 1002) and a droplet-on-demand microfluidic actuator (614a, 614b, 614c, 614d, 1404), wherein the reagent reservoir (612a-d, 622a-d, 632a-d, 804a-d, 902, 1002) is fluidically coupled with the droplet-on-demand microfluidic actuator (614a, 614b, 614c, 614d, 1404); at least one relative motion system configured to move one or more of the sample substrate holder(s) (202, 302, 806), the microfluidic reagent applicator(s) (600, 610, 620, 630, 710, 800, 1102, 1303), the bulk fluid applicator module(s) (116, 306, 400, 420, 500, 520), together or separately; and a reagent storage unit (120, 220, 720); a reagent transport system (122, 700) configured to move the exchangeable fluid reagent reservoirs (612a-d, 622a-d, 632a-d, 804a-d, 902, 1002) between the reagent storage unit (120, 220, 720) and the droplet-on-demand microfluidic actuator (614a, 614b, 614c, 614d, 1404), a control system that is programmed to execute at least one staining protocol on the sample, wherein the control system is configured to control the at least one microfluidic reagent applicator (600, 610, 620, 630, 710, 800, 1102, 1303), the at least one bulk fluid applicator module (116, 306, 400, 420, 500, 520), the at least one sample substrate holder (302, 806), the at least one relative motion system, the reagent storage unit (120, 220, 720), the reagent transport system (122, 700) to execute individual steps of the at least one staining protocol. the at least one microfluidic reagent applicator (600, 610, 620, 630, 710, 800, 1102, 1303), the at least one bulk fluid applicator module (116, 306, 400, 420, 500, 520), the at least one sample substrate holder (302, 806), the at least one relative motion system, the reagent storage unit (120, 220, 720), the reagent transport system (122, 700) to execute individual steps of the at least one staining protocol.