Microfluidic sample preparation: cell lysis and nucleic acid purification

Abstract

Due to the lack of development in the area of sample preparation, few complete lab-on-a-chip systems have appeared in recent years that can deal with raw samples. Cell lysis and nucleic acid extraction systems are sufficiently complex even before adding the complexity of an analysis system. In this review, a variety of microfluidic sample preparation methods are discussed and evaluated. Microsystems for cell lysis are discussed by grouping them into categories based on their lysis mechanisms: mechanical, chemical, thermal or electrical. We classify the nucleic acid purification techniques according to the mechanism that links nucleic acids to substrates: silica-based surface affinity, electrostatic interaction, nanoporous membrane filtration, and functionalized microparticles. The techniques for microfluidic cell lysis and nucleic acid purification are compared based on the ease of microfabrication and integration, and sample flexibility. These assessments can help us determine the appropriate sample preparation technique for generating a true lab-on-a-chip.

On-chip immunoprecipitation for protein purification

“…It would also enable multiplexing of several parallel analysis streams to allow for the simultaneous screening of either multiple samples for the interacting partners of one protein or one sample for many pathway components. Furthermore, a lab-on-a-chip approach to IP would be amenable to integration with upstream sample preparation components, such as cell lysis devices, 5 which would minimise sample handling and therefore loss of proteins due to surface adsorption (a major problem when processing small samples). The analysis of transient interactions, including the characterisation of protein complex subpopulations, would also be improved by the faster processing times offered by such an approach.…”

Integrated electrical concentration and lysis of cells in a microfluidic chip

“…To date, several methods have been demonstrated to lyse cells in microfluidic devices. 1,2 Chemical lysis uses lytic agents such as sodium dodecyl sulfate to dissolve the cell membrane or react with the membrane lipids. [3][4][5] Mechanical lysis uses nanoscale filtrations, 6 spherical particles, 7 or microscale sonication 8 to break down cells with shear and/or frictional forces.…”

Current Developments and Future Trends in Solid-phase Microextraction Techniques for Pharmaceutical and Biomedical Analyses

“…This new device promises a reduced analysis time and reagent consumption, low cost, short reaction time, the ability to integrate multiple functions onto a single device, easy automation and the potential for high-throughput analysis. [139][140][141][142] The chip-based microfluidic concept has greatly promoted the use of nanotechnology in laboratories and hospitals. 140 Many microfluidic systems have been developed to handle multiple procedures for miniaturized analysis, including nucleic acid purification, polymerase chain reaction (PCR), and electrophoretic separation.…”

“…These chip-based microfluidic systems can be widely employed for the purification and enrichment of biological molecules, including DNA, proteins, and peptides, to determine metabolic profiles and genetic transformation. [139][140][141][142][143][144][145][146][147][148] Recently, a microfluidic blood-sampling device using a double-layer PDMS chip was developed for automated collection of nL-size blood samples from mice, and applied to in vivo quantitative small-animal PET analysis. 145 The challenges in this technology are the design of the chip and the incorporation of proper materials for diverse purposes.…”