Electrokinetic sample preconcentration and hydrodynamic sample injection for microchip electrophoresis using a pneumatic microvalve

Cong, Yongzheng; Katipamula, Shanta; Geng, Tao; Prost, Spencer; Tang, Keqi; Kelly, Ryan

doi:10.1002/elps.201500286

Cited by 32 publications

(22 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The geometry issue could also be addressed by integration of the separation channel directly into the chip (instead of using a capillary); this would eliminate the junctions altogether and simplify the overall setup, enabling a single integrated microfluidic device for injection, separation, and detection. Separation in PDMS channels has been reported by several groups [54, 55], though some have reported challenges in maintaining stable surface conditioning [56, 57]. An alternative may be to perform separation using an embedded capillary [58, 59].…”

Section: Resultsmentioning

confidence: 99%

Toward miniaturized analysis of chemical identity and purity of radiopharmaceuticals via microchip electrophoresis

Cheung

et al. 2018

Anal Bioanal Chem

View full text Add to dashboard Cite

Miniaturized synthesis of positron emission tomography (PET) tracers is poised to offer numerous advantages including reduced tracer production costs and increased availability of diverse tracers. While many steps of the tracer production process have been miniaturized, there has been relatively little development of microscale systems for the quality control (QC) testing process that is required by regulatory agencies to ensure purity, identity, and biological safety of the radiotracer before use in human subjects. Every batch must be tested, and in contrast with ordinary pharmaceuticals, the whole set of tests of radiopharmaceuticals must be completed within a short-period of time to minimize losses due to radioactive decay. By replacing conventional techniques with microscale analytical ones, it may be possible to significantly reduce instrument cost, conserve lab space, shorten analysis times, and streamline this aspect of PET tracer production. We focus in this work on miniaturizing the subset of QC tests for chemical identity and purity. These tests generally require high-resolution chromatographic separation prior to detection to enable the approach to be applied to many different tracers (and their impurities), and have not yet, to the best of our knowledge, been tackled in microfluidic systems. Toward this end, we previously explored the feasibility of using the technique of capillary electrophoresis (CE) as a replacement for the "gold standard" approach of using high-performance liquid chromatography (HPLC) since CE offers similar separating power, flexibility, and sensitivity, but can readily be implemented in a microchip format. Using a conventional CE system, we previously demonstrated the successful separation of non-radioactive version of a clinical PET tracer, 3'-deoxy-3'-fluorothymidine (FLT), from its known by-products, and the separation of the PET tracer 1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-cytosine (D-FAC) from its α-isomer, with sensitivity nearly as good as HPLC. Building on this feasibility study, in this paper, we describe the first effort to miniaturize the chemical identity and purity tests by using microchip electrophoresis (MCE). The fully automated proof-of-concept system comprises a chip for sample injection, a separation capillary, and an optical detection chip. Using the same model compound (FLT and its known by-products), we demonstrate that samples can be injected, separated, and detected, and show the potential to match the performance of HPLC. Addition of a radiation detector in the future would enable analysis of radiochemical identity and purity in the same device. We envision that eventually this MCE method could be combined with other miniaturized QC tests into a compact integrated system for automated routine QC testing of radiopharmaceuticals in the future. Graphical abstract Miniaturized quality control (QC) testing of batches of radiopharmaceuticals via microfluidic analysis. The proof-of-concept hybrid microchip electrophoresis (MCE) device demonstrated the fea...

show abstract

Section: Resultsmentioning

confidence: 99%

Toward miniaturized analysis of chemical identity and purity of radiopharmaceuticals via microchip electrophoresis

Cheung

et al. 2018

Anal Bioanal Chem

View full text Add to dashboard Cite

show abstract

“…Indeed, Cong et al [42] developed an electrokinetic sample preconcentration microfluidic device with electrokinetic or hydrodynamic injection, a pneumatic valve for preconcentration and µCE separation. With the valve closed during electrokinetic injection, current flowed but bulk flow was blocked, allowing ion concentration polarization for sample preconcentration at the closed valve interface.…”

Section: On-chip Sample Preparation Methodsmentioning

confidence: 99%

Recent advances in microfluidic sample preparation and separation techniques for molecular biomarker analysis: A critical review

Sonker

Sahore

Woolley

2017

Analytica Chimica Acta

141

View full text Add to dashboard Cite

Microfluidics is a vibrant and expanding field that has the potential for solving many analytical challenges. Microfluidics show promise to provide rapid, inexpensive, efficient, and portable diagnostic solutions that can be used in resource-limited settings. Researchers have recently reported various microfluidic platforms for biomarker analysis applications. Sample preparation processes like purification, preconcentration and labeling have been characterized on-chip. Additionally, improvements in microfluidic separation techniques have been reported for cellular and molecular biomarkers. This review critically evaluates microfluidic sample preparation platforms and separation methods for biomarker analysis reported in the last two years. Key advances in device operation and ability to process different sample matrices in a variety of device materials are highlighted. Finally, current needs and potential future directions for microfluidic device development to realize its full diagnostic potential are discussed.

show abstract

“…The sample can be driven by hydrostatic pressure [38], with a syringe pump [39], or by applying positive or negative pressure to the sample well [40,41]. A variety of other “plug shaping” techniques have been developed to reduce the sample volume and/or avoid sample “leakage” [39,42], or to improve control of the sample volume [43], but they tend to add complexity and sometimes introduce injection biases.…”

Section: Introductionmentioning

confidence: 99%

“…One approach is to use microvalve-based chips [44], typically made from poly(dimethylsiloxane) (PDMS). The basic concept is to apply constant pressure to the sample and use a computer-controlled microvalve that can be momentarily opened to inject the sample into the separation channel [40,42]. Such valve-based approaches exhibit repeatable sample injection, yielding RSD of the peak area in the range of 1.76 to 5% [32,45,46].…”

Section: Introductionmentioning

confidence: 99%

Novel volumetric method for highly repeatable injection in microchip electrophoresis

Jones

et al. 2017

Analytica Chimica Acta

View full text Add to dashboard Cite

A novel injector for microchip electrophoresis (MCE) has been designed and evaluated that achieves very high repeatability of injection volume suitable for quantitative analysis. It eliminates the injection biases in electrokinetic injection and the dependence on pressure and sample properties in hydrodynamic injection. The microfluidic injector, made of poly(dimethylsiloxane) (PDMS), operates similarly to an HPLC injection valve. It contains a channel segment (chamber) with a well-defined volume that serves as an “injection loop”. Using on-chip microvalves, the chamber can be connected to the sample source during the “loading” step, and to the CE separation channel during the “injection” step. Once the valves are opened in the second state, electrophoretic potential is applied to separate the sample. For evaluation and demonstration purposes, the microinjector was connected to a 75 µm ID capillary and UV absorbance detector. For single compounds, a relative standard deviation (RSD) of peak area as low as 1.04% (n=11) was obtained, and for compound mixtures, RSD as low as 0.40% (n=4) was observed. Using the same microchip, the performance of this new injection technique was compared to hydrodynamic injection and found to have improved repeatability and less dependence on sample viscosity. Furthermore, a non-radioactive version of the positron-emission tomography (PET) imaging probe, FLT, was successfully separated from its known 3 structurally-similar byproducts with baseline resolution, demonstrating the potential for rapid, quantitative analysis of impurities to ensure the safety of batches of short-lived radiotracers. Both the separation efficiency and injection repeatability were found to be substantially higher when using the novel volumetric injection approach compared to electrokinetic injection (performed in the same chip). This novel microinjector provides a straightforward way to improve the performance of hydrodynamic injection and enables extremely repeatable sample volume injection in MCE. It could be used in any MCE application where volume repeatability is needed, including the quantitation of impurities in pharmaceutical or radiopharmaceutical samples.

show abstract

Electrokinetic sample preconcentration and hydrodynamic sample injection for microchip electrophoresis using a pneumatic microvalve

Cited by 32 publications

References 44 publications

Toward miniaturized analysis of chemical identity and purity of radiopharmaceuticals via microchip electrophoresis

Toward miniaturized analysis of chemical identity and purity of radiopharmaceuticals via microchip electrophoresis

Recent advances in microfluidic sample preparation and separation techniques for molecular biomarker analysis: A critical review

Novel volumetric method for highly repeatable injection in microchip electrophoresis

Contact Info

Product

Resources

About