3D printed extraction devices in the analytical laboratorya case study of Soxhlet extraction

[eng] 3D printing was introduced in the 1980s but only now has gained widespread acceptance among practitioners because of (i) the friendlier software interfaces for digital computer-assisted designs (CAD), and the ensuing computer-assisted manufacturing (CAM) of the 3D object; (ii) availability of low-cost custom-grade printers; and (iii) the advantages that present against milling or other classical subtractive technologies, that is, enables complicated geometries to be easily designed in a single step, generates minimum residues, and allows fast prototyping. Chemists have followed this trend and incorporated 3D printers in their research laboratories and lecture halls, demonstrating the possibilities of this technique in a plethora of academic publications

Opportunities for 3D printed millifluidic platforms incorporating on-line sample handling and separation

3D printing is an emerging enabling technology that can facilitate the production of complex 3D structures in analytical chemistry, including the millifluidic, e.g. flow injection (FI), and microfluidic arenas. In this review, the potential of 3D printing for the fabrication of cost-effective millifluidic platforms incorporating on-line sample handling and separation is critically appraised against traditional configurations or manufacturing processes. Applications resorting to structures achievable with 3D printing, in some instances exploiting the surface chemistry of the printable material, are grouped under: (i) fluidic drivers, mixers and reactors, (ii) membrane separation, (iii) sorbent extraction/concentration, (iv) chromatographic and electrophoretic separation, and (v) sensing and detector housings. Summary tables are also presented for reported applications of on-line sample handling and separation in environmental and biochemical analysis

3D printing in separation science: Hype or reality

[eng] Three-dimensional (3D) printing is an emerging and enabling technology that is paving its way in different fields of research, including analytical science, for the fabrication of custom devices and portable sensing platforms based on additive manufacturing of objects from Computer-Aided Design (CAD) models. In fact, the last five years have witnessed tremendous advances in novel materials and composites with improved chemical properties (e.g., noble metals, carbon nanomaterials, and chemically resistant polymers). Printing platforms for fabrication of low-cost devices have capitalized on stereolithography (SLA) or dynamic light processing (DLP), inkjet printing, fused deposition modelling (FDM), and selective laser sintering (SLS) that enable decentralized (in situ) measurements. The main advantage of 3D printing is the capability of rapid and single-step prototyping of holders, scaffolds, and integrated complex systems with geometries that cannot easily be manufactured by conventional means, such as computer numerical controlled milling and soft-lithographic approaches. Furthermore, the outreach of this technique has been expanded by the lowering costs of the machinery, the user-friendliness of the CAD software and especially the commercial strategies addressed to the nontechnical and nonscientific collective, currently called the 'maker community'

Opportunities for 3D printed millifluidic platforms incorporating on-line sample handling and separation

3D printing is an emerging enabling technology that can facilitate the production of complex 3D structures in analytical chemistry, including the millifluidic, e.g. flow injection (FI), and microfluidic arenas. In this review, the potential of 3D printing for the fabrication of cost-effective millifluidic platforms incorporating on-line sample handling and separation is critically appraised against traditional configurations or manufacturing processes. Applications resorting to structures achievable with 3D printing, in some instances exploiting the surface chemistry of the printable material, are grouped under: (i) fluidic drivers, mixers and reactors, (ii) membrane separation, (iii) sorbent extraction/concentration, (iv) chromatographic and electrophoretic separation, and (v) sensing and detector housings. Summary tables are also presented for reported applications of on-line sample handling and separation in environmental and biochemical analysis

In-line carbon nanofiber reinforced hollow fiber-mediated liquid phase microextraction using a 3D printed extraction platform as a front end to liquid chromatography for automatic sample preparation and analysis: A proof of concept study

A novel concept for automation of nanostructured hollow-fiber supported microextraction, combining the principles of liquid-phase microextraction (LPME) and sorbent microextraction synergically, using mesofluidic platforms is proposed herein for the first time, and demonstrated with the determination of acidic drugs (namely, ketoprofen, ibuprofen, diclofenac and naproxen) in urine as a proof-of-concept applicability. Dispersed carbon nanofibers (CNF) are immobilized in the pores of a single-stranded polypropylene hollow fiber (CNF@HF) membrane, which is thereafter accommodated in a stereolithographic 3D-printed extraction chamber without glued components for ease of assembly. The analytical method involves continuous-flow extraction of the acidic drugs from a flowing stream donor (pH 1.7) into an alkaline stagnant acceptor (20 mmol L−1 NaOH) containing 10% MeOH (v/v) across a dihexyl ether impregnated CNF@HF membrane. The flow setup features entire automation of the microextraction process including regeneration of the organic film and on-line injection of the analyte-laden acceptor phase after downstream neutralization into a liquid chromatograph (LC) for reversed-phase core-shell column-based separation. Using a 12-cm long CNF@HF and a sample volume of 6.4 mL, linear dynamic ranges of ketoprofen, naproxen, diclofenac and ibuprofen, taken as models of non-steroidal anti-inflammatory drugs, spanned from ca. 5-15 µg L−1 to 500 µg L−1 with enhancement factors of 43-97 (against a direct injection of 10 µL standards into LC), and limits of detection from 1.6 to 4.3 µg L−1. Relative recoveries in real urine samples ranged from 97% to 105%, thus demonstrating the reliability of the automatic CNF@HF-LPME method for in-line matrix clean-up and determination of drugs in urine at therapeutically relevant concentrations

Automatic Kinetic Bioaccessibility Assay of Lead in Soil Environments Using Flow-through Microdialysis as a Front End to Electrothermal Atomic Absorption Spectrometry

In-line microdialysis is in this work hyphenated to electrothermal atomic absorption spectrometry via a dedicated flow-based interface for monitoring the batchwise leaching test endorsed by the Standards, Measurements and Testing Program (SM&T) of the European Commission. The bioaccessible pool of lead in soils is measured using 0.43 mol/L AcOH as extractant. The proposed method allows to gain knowledge of leaching kinetics at real-time, simplify the overall procedure by accurate detection of steady-state conditions and overcome sample filtration or centrifugation. Soil leachates were automatically sampled at specified timeframes (e.g, every 20 or 80 min), processed in an external container (where dilution can be applied at will) and further injected into the atomizer. The method was experimentally validated by comparison of <i>in situ</i> microdialysis sampling results with in-line microfiltration in two soils of varying physicochemical properties. A mathematical framework was used for discrimination of different metal fractions (that is, readily mobilizable against slowly mobilizable lead) and also for estimating the total extractable lead under actual steady-state conditions. We have demonstrated that bioaccessibility tests lasting 16 h as endorsed by SM&T might not suffice for ascertainment of maximum (steady-state) bioaccessibility of lead in terrestrial environments as demanded in risk assessment programs

3D Printing: The Second Dawn of Lab-On-Valve Fluidic Platforms for Automatic (Bio)Chemical Assays

In this work, inexpensive manufacturing of unibody transparent mesofluidic platforms for pressure-driven Lab-On-a-Valve (LOV) methodologies is accomplished via rapid one-step 3D prototyping from digital models by user-friendly freeware. Multichannel architecture having 800-1800 μm cross-sectional features with unconventional 3D conduit structures and integrating optical and electrochemical detection facilities is for the first time reported. User-defined flow-programming capitalizing upon software control for automatic liquid handling is synergistically combined with additive manufacturing based on stereolithographic 3D printing so as to launch the so-called fourth generation of microflow analysis (3D-μFIA). Using an affordable consumer-grade 3D printer dedicated LOV platforms are 3D printed at will and prints are characterized in terms of solvent compatibility, optical and mechanical properties, and sorption of inorganic and organic species to prospect potentialities for the unfettered choice of chemistries. The unique versatility of the 3D-printed LOV device that is attached to a multiposition rotary valve as a central design unit is demonstrated by (i) online handling of biological materials followed by on-chip photometric detection, (ii) flow-through bioaccessibility tests in exposome studies of contaminated soils with miniaturized voltammetric detection, (iii) online phospholipid removal by TiO2-incorporated microextraction approaches using on-chip disposable sorbents, and (iv) automatic dynamic permeation tests mimicking transdermal measurements in Franz-cell configurations. A multipurpose LOV fluidic platform can be fabricated for less than 11 Euros

In quest of effect directed analysis at the smart laboratory: Automated system for flow-through evaluation of membranotropic effects of emerging contaminants

[eng] The rate-determining step of the human exposome workflow is the acquisition of physiologically relevant data (e.g., effect directed analysis), which can be performed retrospectively or with ad hoc experiments. In this contribution, an automated system is proposed for evaluating potential interaction mechanisms of xenobiotics across cell membranes, the so-called membranotropic effects, using liposomes as a mimicry of biological membranes, and fluorescent membrane probes. The smart fluidic method features real-time acquisition of fluorescence readouts, data processing and feedback in a fully unsupervised mode. As a proof of concept applicability, the behavior of newly synthesized cholesterol-laden biomimetic liposomes, and the in-vitro potential toxicant action of bisphenol A and diclofenac as model of emerging contaminants on cell membrane surrogates were investigated in a flow-through format. Unattended operation resulted in excellent intermediate precision (<1.5%) and unveiled that diclofenac affected the liposomal bilayer order very slightly, regardless of the cholesterol concentration, because it accumulates at a superficial level, while the membranotropic effect of bisphenol A was more pronounced at low concentration levels of cholesterol because at increased levels, the membrane reduces its permeability

On-line monitorování in-vitro testu orální biodosažitelnosti s následnou kapalinovou chromatografií pro stanovení izomerů kyseliny chlorogenové v doplňcích stravy

A novel fully automated in-vitro oral dissolution test assay as a front-end to liquid chromatography has been developed and validated for on-line chemical profiling and monitoring of temporal release profiles of three caffeoylquinic acid (CQA) isomers,namely, 3-CQA,4-CQA and 5-CQA, known as chlorogenic acids, in dietary supplements. Tangential-flow filtration is harnessed as a sample processing approach for on-line handling of CQA containing extracts of hard gelatin capsules and introduction of protein-free samples into the liquid chromatograph. Oral bioaccessibility/dissolution test assays were performed at 37.0±0.5 °C as per US Pharmacopeia recommendations using pepsin with activity of ca. 749,000 USP units/L in 0.1 mol/L HCl as the extraction medium and a paddle apparatus stirred at 50 rpm. CQA release rates and steady-state dissolution conditions were determined accurately by fitting the chromatographic datasets, namely, the average cumulative concentrations of bioaccessible pools of every individual isomer monitored during 200 min, with temporal resolutions of ≥10 min, to a first-order dissolution kinetic model. Distinct solid-to-liquid phase ratios in the mimicry of physiological extraction conditions were assessed. Relative standard deviations for intra-day repeatability and inter-day intermediate precision of 5-CQA within the 5–40 µg/mL concentration range were &lt;3.4% and &lt;5.5%, respectively. Trueness of the automatic flow method for determination of 5-CQA released from dietary supplements in gastric fluid surrogate was demonstrated by spike recoveries, spanning from 91.5–104.0%, upon completion of the dissolution process. The proposed hyphenated setup was resorted for evaluating potential differences in dissolution profiles and content of the three most abundant chlorogenic acid isomers in dietary supplements from varied manufacturers.Nový plně automatizovaný in-vitro orální rozpouštěcí test s následnou kapalinovou chromatografií byl vyvinut a optimalizován pro on-line chemické profilování a monitorování časových profilů uvolňování tří izomerů kafeoylchinových kyselin (CQA), a to jmenovitě 3-CQA, 4-CQA a 5-CQA, známých jako chlorogenové kyseliny, v doplňcích stravy. Ke zpracování vzorků byla použita metoda tangenciální filtrace pro on-line sběr CQA obsahujících extraktů tvrdých želatinových kapslí a zavedení vzorků prostých od bílkovin do kapalinového chromatografu. Test orální biodosažitelnosti/rozpouštění byl prováděn při 37,0±0,5 °C dle doporučení US Pharmacopeia využívající pepsin s aktivitou cca 749 000 USP jednotek/l v 0,1 mol/l HCl jako extrakčním mediu a v lopatkovém aparátku míchaném rychlostí 50 ot./min. Rychlost uvolňování CQA a rovnovážný stav rozpouštění byly přesně stanoveny z chromatografických souborů dat, konkrétně průměrných kumulativních koncentrací každého izomeru sledovaných během 200 min., s časovým rozlišením ≥10 min, vzhledem ke kinetickému rozpouštěcímu modelu prvního řádu. Byly hodnoceny různé poměry tuhé a kapalné fáze v podmínkách simulace fyziologické extrakce. Relativní směrodatné odchylky pro opakovatelnost (intra-day) a mezilehlou přesnost (inter-day) pro 5-CQA na koncentrační úrovni 40 µg/ml byly do 3,4 % a do 5,5 %. Správnost automatické průtokové metody pro stanovení 5-CQA uvolněné z potravinových doplňků v náhražce žaludečních tekutin byla demonstrována metodou standardního přídavku a byla v rozmezí 91,5-104,0 % po dokončení rozpouštěcího procesu. Navržené uspořádání bylo využito pro hodnocení možných rozdílů v rozpouštěcích profilech a obsahu tří nejběžnějších izomerů kyseliny chlorogenové v potravinových doplňcích od různých výrobců