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Title: Novel volumetric method for highly repeatable injection in microchip electrophoresis

Journal Article · · Analytica Chimica Acta
 [1];  [1];  [2];  [3]; ORCiD logo [4]
  1. Univ. of California, Los Angeles, CA (United States). Dept. of Bioengineering. Henry Samueli School of Engineering and Applied Science. Crump Inst. for Molecular Imaging. Dept. of Molecular and Medical Pharmacology. David Geffen School of Medicine
  2. Univ. of California, Los Angeles, CA (United States). Crump Inst. for Molecular Imaging. Dept. of Molecular and Medical Pharmacology. David Geffen School of Medicine. Physics & Biology in Medicine Interdepartmental Graduate Program
  3. Univ. of California, Los Angeles, CA (United States). Crump Inst. for Molecular Imaging. Dept. of Molecular and Medical Pharmacology. David Geffen School of Medicine
  4. Univ. of California, Los Angeles, CA (United States). Dept. of Bioengineering. Henry Samueli School of Engineering and Applied Science. Crump Inst. for Molecular Imaging. Dept. of Molecular and Medical Pharmacology. David Geffen School of Medicine. Physics & Biology in Medicine Interdepartmental Graduate Program

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.

Research Organization:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
SC0001249
OSTI ID:
1533446
Alternate ID(s):
OSTI ID: 1566180
Journal Information:
Analytica Chimica Acta, Vol. 985; ISSN 0003-2670
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 10 works
Citation information provided by
Web of Science

References (60)

Comparison between capillary electrophoresis and HPLC-FL for ochratoxin A quantification in wine journal July 2006
How to achieve higher repeatability and reproducibility in capillary electrophoresis journal August 1999
Simultaneous analysis of enzyme structure and activity by kinetic capillary electrophoresis–MS journal September 2016
Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review journal September 2016
Capillary electrophoresis applied to DNA: determining and harnessing sequence and structure to advance bioanalyses (2009–2014) journal May 2015
Application of capillary electrophoresis for the early diagnosis of cancer journal March 2014
Strong Anion Determination in Biological Fluids by Capillary Electrophoresis for Clinical Diagnostics journal October 2013
Effect of ionic liquids on the interaction between liposomes and common wastewater pollutants investigated by capillary electrophoresis journal July 2015
Development and evaluation of a microdevice for amino acid biomarker detection and analysis on Mars journal January 2005
The potential of the capillary electrophoresis techniques for quality control of biopharmaceuticals-A review: CE and CEC journal February 2015
The application of portable microchip electrophoresis for the screening and comparative analysis of synthetic cathinone seizures journal September 2014
Recent advances of capillary electrophoresis in pharmaceutical analysis journal May 2010
Present state of microchip electrophoresis: State of the art and routine applications journal February 2015
Scaling and the design of miniaturized chemical-analysis systems journal July 2006
Review on the development of truly portable and in-situ capillary electrophoresis systems journal February 2013
Capillary and microchip electrophoresis: Challenging the common conceptions journal January 2012
Applications of microfluidics and microchip electrophoresis for potential clinical biomarker analysis journal April 2015
Recent advances in miniaturisation - The role of microchip electrophoresis in clinical analysis journal November 2011
Chip-based separation devices coupled to mass spectrometry journal August 2012
Compact microfluidic device for rapid concentration of PET tracers journal January 2014
Microfluidics: A Groundbreaking Technology for PET Tracer Production? journal July 2013
Development of fully automated quantitative capillary electrophoresis with high accuracy and repeatability: Development of fully automated quantitative capillary electrophoresis journal September 2015
How to increase precision in capillary electrophoresis journal January 2001
Parameters affecting reproducibility in capillary electrophoresis journal April 2000
Why not using capillary electrophoresis in drug analysis? journal June 2006
Analytical instrument qualification in capillary electrophoresis: CE and CEC journal June 2012
Quantitative capillary electrophoresis and its application in analysis of alkaloids in tea, coffee, coca cola, and theophylline tablets journal December 2008
Sample Injection for Capillary Electrophoresis on a Micro Fabricated Device/On Chip CE Injection journal January 2006
Sample introduction techniques for microchip electrophoresis: A review journal May 2012
Instrumentation design for hydrodynamic sample injection in microchip electrophoresis: A review: Microfluidics and Miniaturization journal September 2012
Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2010-2012): CE and CEC journal January 2013
Sequential injection sample introduction microfluidic-chip based capillary electrophoresis system journal May 1999
Calibration principles for flow injection analysis–capillary electrophoresis systems with electrokinetic injection journal May 1998
Double-Cross Hydrostatic Pressure Sample Injection for Chip CE:  Variable Sample Plug Volume and Minimum Number of Electrodes journal September 2006
A simple approach to the hydrodynamic injection in microchip electrophoresis with electrochemical detection journal July 2010
Pneumatic Microvalve-Based Hydrodynamic Sample Injection for High-Throughput, Quantitative Zone Electrophoresis in Capillaries journal June 2014
Electrokinetic sample preconcentration and hydrodynamic sample injection for microchip electrophoresis using a pneumatic microvalve: Microfluidics and Miniaturization journal November 2015
Split injection: A simple introduction of subnanoliter sample volumes for chip electrophoresis journal November 2011
Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography journal April 2000
Design and Characterization of Poly(dimethylsiloxane)-Based Valves for Interfacing Continuous-Flow Sampling to Microchip Electrophoresis journal February 2006
Generation of Nonbiased Hydrodynamic Injections on Microfluidic Devices Using Integrated Dielectric Elastomer Actuators journal October 2009
Integration of on-chip peristaltic pumps and injection valves with microchip electrophoresis and electrochemical detection journal July 2010
Pressure Injection on a Valved Microdevice for Electrophoretic Analysis of Submicroliter Samples journal April 2005
Pressure-actuated microfluidic devices for electrophoretic separation of pre-term birth biomarkers journal November 2015
Pressure Pulse Injection:  a Powerful Alternative to Electrokinetic Sample Loading in Electrophoresis Microchips journal April 2003
A Complete Microfluidic Screening Platform for Rational Protein Crystallization journal January 2007
Scaling properties of a low-actuation pressure microfluidic valve journal January 2004
Sodium hydroxide treatment of PDMS based microfluidic devices journal January 2010
Microfluidic device for robust generation of two-component liquid-in-air slugs with individually controlled composition journal April 2010
Simple preparation and purification of ethanol-free solutions of 3′-deoxy-3′-[18F]fluorothymidine by means of disposable solid-phase extraction cartridges journal May 2012
The separation and detection of PET tracers via capillary electrophoresis for chemical identity and purity analysis journal June 2014
Injection by hydrostatic pressure in conjunction with electrokinetic force on a microfluidic chip journal June 2004
Bias in quantitative capillary zone electrophoresis caused by electrokinetic sample injection journal February 1988
Microchip electrophoresis with hydrodynamic injection and waste-removing function for quantitative analysis journal October 2004
Viscosity of aqueous NaCl solutions in the temperature range 25?200 �C and in the pressure range 0.1?30 MPa journal September 1984
Viscosity of liquid water in the range −8 °C to 150 °C journal July 1978
Formula for the Viscosity of a Glycerol−Water Mixture journal May 2008
On-demand generation and mixing of liquid-in-gas slugs with digitally programmable composition and size journal July 2015
Microfluidic Devices Connected to Fused-Silica Capillaries with Minimal Dead Volume journal August 1999
Minimal dead-volume connectors for microfluidics using PDMS casting techniques journal August 2004

Cited By (1)

Recent Progress toward Microfluidic Quality Control Testing of Radiopharmaceuticals journal November 2017