On-chip electro membrane extraction

Abstract

This paper presents the first downscaling of electro membrane extraction (EME) to a chip format. The voltage-controlled extraction for sample preparation on microfluidic devices has several advantages such as selective extraction removing the high ionic strength of biological samples, preconcentration, fast kinetics with exact control of the beginning, and termination of the extraction. The device comprises a 25 lm thick porous polypropylene membrane bonded in-between two polymethyl methacrylate (PMMA) substrates with channel structures toward the membrane. The supported liquid membrane (SLM) was created by locally filling the pores of the membrane with 2-nitrophenyl octyl ether (NPOE). The sample solution, containing five basic model analytes in 10 mM HCl or urine was pumped through the 50 lm deep donor channel on one side of the membrane. With 15 V applied across the membrane, the protonated basic drugs were selectively extracted from the flowing sample solution, into the organic phase SLM, and further into just 7 ll of 10 mM HCl, serving as acceptor solution. Subsequently, the acceptor solution was analyzed by capillary electrophoresis. The electro membrane chip was highly efficient and even with flow rates resulting in the sample being in contact with the SLM for less than 4 s (3 ll min -1 ), 20-60% of the amount of the respective drugs in the sample was extracted. The large span in recovery was dependent on the physical properties of the drug substances compared to the SLM, and the individual drug substances were extracted with a RSD in the recovery of less than 5%.

Electromembrane Extraction from Biological Fluids

“…This has been verified experimentally in several EME papers, 10,20,[23][24][25]27,29,[31][32][33][34] where recoveries have been found to increase with increasing voltage up to a certain level. The latter point out that extraction is limited by other factors than the voltage at high voltages, and deviations from Eq.…”

“…[31][32][33] In one configuration, urine samples containing different basic drugs were pumped at 2.5 μl/min into the sample channel of a micro-chip. 32 This sample channel was in direct contact with a small SLM (NPOE), sustained in a small piece of a flat polypropylene membrane, and the drugs were extracted across this SLM and into a small reservoir on the other side containing 7 μl of 10 mM HCl (acceptor phase). This acceptor phase was subsequently collected by a micro-pipette, transferred to a micro-vial, and analyzed off-line by CE.…”

“…In the chip format the same SLM could be used for several days without carryover or loss in performance. 32,33 Finally, EME provides very efficient sample clean-up of biological samples as illustrated in Fig. 3.…”

“…18 Several of the developed EME methods have been validated, and have provided acceptable results from human plasma, whole blood, urine, saliva, and breast milk. 10,[17][18][19][20][21][22][23][24][25]28,31,32 Typically, the EME methods have provided linear calibration curves over 2 decades (r 2 > 0.99) 22,24 and with repeatability values in the range 2 -10% RSD. 22,24 One example of validation results are reported in Table 1 for naltrexone and nalmefene in human plasma and urine.…”

“…The membranes used in EME until date has been 200 μm with hollow fibers 10 or 25 μm with flat membranes in the drop to drop or micro-chip systems. [31][32][33] Thinner membranes may be interesting to test in the future to improve performance, but the mechanical stability may be an issue for very thin membranes.…”