BackgroundSolid phase extraction (SPE) is a standard sample preparation technique in HPLC workflows. Inline cartridges are a high-performance alternative to manual or robotic workflows but at long term, suffer from irreversible sorption of matrix components and sorbent compaction. Bead injection is a niche fluidic technique that allows to renew a sorbent bed through the manipulation of its suspension. Until now it has never been applied inline to HPLC workflows because of the irreproducibility when trying to aspirate a compacted sorbent. There is a need for a tool in HPLC that can exchange the inline sorbent automatically, resorting to inexpensive and assorted bulk sorbents. ResultsWe present a new flowpath for a liquid chromatographic injector to perform inline micro-solid phase extraction. The sample is processed at real time trapping the analytes and discarding the matrix. Cleaning the matrix and injecting 10 μL of sample takes 70 s, comparable with the injection in commercial HPLC systems. If the aim is to preconcentrate the analytes, average enrichment factors of 250 have been obtained after processing volumes of 3200 μL in 16 min (interleavable with the chromatographic step), keeping the peak position and width independent of the injected volume (compared to large volume direct injection).The desired bed mass is automatically and pressure-driven manipulated in the valve, retained by an inline frit, and optionally, after the analysis, removed by forward flow.The chromatographic performance of the new design is compared to the standard 6-port, 2-position injector. As an application example, we monitored the extraction kinetics of a bioaccessibility extraction test of organic contaminants in soil, by extracting several fractions in valve, process them with SPE with a balanced hydrophilic-hydrophobic reversed-phase sorbent and inject them into HPLC. Aiming at avoiding carryover, the 3 mg sorbent bed was exchanged before every run. It should be noted that this contribution focuses on HPLC, but other non-separative techniques, such as Flow Injection Analysis, can equally benefit from this injection platform. SignificanceThis contribution reports the first use of inline solid phase extraction in HPLC workflows in which the sorbent can be exchanged automatically, based on a fluidic approach. This performance is enabled by prototyping a valve that can autonomously swap sorbents in real-time for diverse samples, as a cartridge exchanger, but using cost-effective and environmentally friendlier bulk sorbents (bed masses from sub-mg to 5 mg) without requiring additional hardware.