A fully automatic millifluidic sensing platform coupling in-line nonsupported microelectromembrane extraction (μ-EME) with electrochemical detection (ECD) is herein proposed for the first time. Exploiting the features of the second generation of flow analysis, termed sequential injection (SI), the smart integration of SI and μ-EME-ECD enables (i) the repeatable formation of microvolumes of phases for the extraction step in a membrane-less (nonsupported) arrangement, (ii) diverting the acceptor plug to the ECD sensing device, (iii) in-line pH adjustment before the detection step, and (iv) washing of the platform for efficient removal of remnants of wetting film solvent, all entirely unsupervised. The real-life applicability of the miniaturized sensing system is studied for in-line sample cleanup and ECD of diclofenac as a model analyte after μ-EME of urine as a complex biological sample. A comprehensive study of the merits and the limitations of μ-EME solvents on ECD is presented. Under the optimal experimental conditions using 14 μL of unprocessed urine as the donor, 14 μL of 1-nonanol as the organic phase, and 14 μL of 25 mM NaOH as the acceptor in a 2.4 mm ID PTFE tubing, an extraction voltage of 250 V, and an extraction time of 10 min, an absolute (mass) extraction recovery of 48% of diclofenac in urine is obtained. The proposed flow-through system is proven to efficiently remove the interfering effect of predominantly occurring organic species in human urine on ECD with RSD% less than 8.6%.

• Keywords
• automation, diclofenac, electrochemical sensing, nonsupported electrically driven extraction, sequential injection analysis,
• MeSH
• Diclofenac * MeSH
• Humans MeSH
• Membranes, Artificial * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Diclofenac * MeSH
• Membranes, Artificial * MeSH

We report on the hyphenation of the modern flow techniques Lab-In-Syringe and Lab-On-Valve for automated sample preparation coupled online with high-performance liquid chromatography. Adopting the bead injection concept on the Lab-On-Valve platform, the on-demand, renewable, solid-phase extraction of five nonsteroidal anti-inflammatory drugs, namely ketoprofen, naproxen, flurbiprofen, diclofenac, and ibuprofen, was carried out as a proof-of-concept. In-syringe mixing of the sample with buffer and standards allowed straightforward pre-load sample modification for the preconcentration of large sample volumes. Packing of ca. 4.4 mg microSPE columns from Oasis HLB® sorbent slurry was performed for each sample analysis using a simple microcolumn adapted to the Lab-On-Valve manifold to achieve low backpressure during loading. Eluted analytes were injected into online coupled HPLC with subsequent separation on a Symmetry C18 column in isocratic mode. The optimized method was highly reproducible, with RSD values of 3.2% to 7.6% on 20 µg L-1 level. Linearity was confirmed up to 200 µg L-1 and LOD values were between 0.06 and 1.98 µg L-1. Recovery factors between 91 and 109% were obtained in the analysis of spiked surface water samples.

• Keywords
• Lab-In-Syringe, Lab-On-Valve, bead injection, high-performance liquid chromatography, nonsteroidal anti-inflammatory drugs, online coupling, water analysis,
• MeSH
• Anti-Inflammatory Agents, Non-Steroidal analysis   MeSH
• Solid Phase Extraction * MeSH
• Surface Properties MeSH
• Water chemistry   MeSH
• Chromatography, High Pressure Liquid MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Inflammatory Agents, Non-Steroidal MeSH
• Water MeSH

About eight years ago, a new automation approach and flow technique called "Lab-In-Syringe" was proposed. It was derived from previous flow techniques, all based on handling reagent and sample solutions in a flow manifold. To date Lab-In-Syringe has evidently gained the interest of researchers in many countries, with new modifications, operation modes, and technical improvements still popping up. It has proven to be a versatile tool for the automation of sample preparation, particularly, liquid-phase microextraction approaches. This article aims to assist newcomers to this technique in system planning and setup by overviewing the different options for configurations, limitations, and feasible operations. This includes syringe orientation, in-syringe stirring modes, in-syringe detection, additional inlets, and addable features. The authors give also a chronological overview of technical milestones and a critical explanation on the potentials and shortcomings of this technique, calculations of characteristics, and tips and tricks on method development. Moreover, a comprehensive overview of the different operation modes of Lab-In-Syringe automated sample pretreatment is given focusing on the technical aspects and challenges of the related operations. We further deal with possibilities on how to fabricate required or useful system components, in particular by 3D printing technology, with over 20 different elements exemplarily shown. Finally, a short discussion on shortcomings and required improvements is given.

• Keywords
• 3D printing of instrument elements, Lab-In-Syringe, automation of sample pretreatment, potentials and troubles, system setup and operation modes, tips and tricks in method development,
• MeSH
• Chemistry Techniques, Analytical instrumentation   methods   standards   MeSH
• Syringes * MeSH
• Automation, Laboratory * MeSH
• Limit of Detection MeSH
• Reproducibility of Results MeSH
• Publication type
• Journal Article MeSH