Biofunctionalization of Glass‐ and Paper‐Based Microfluidic Devices: A Review

Abstract

Biofunctionalization of microchannels is of great concern in the fabrication of microfluidic devices. Different substrates such as glass slides, papers, polymers, and beads require different biofunctionalization approaches granting the utilization of microfluidics in several biomedical applications. Covalent immobilization of biomolecules inside the microchannels is achieved by chemical modification of the surface such as silanization or introducing different coupling agents. Although creating biointerfaces that are covalently bonded to the microchannel surface necessitates multiple steps of surface modification and incubation times, it bestows a robust biointerface capable of withstanding high shear stresses and harsh conditions without dissipating the biofunctionality. Regarding the applications that do not require robustness and long‐term stability, noncovalent attachment of biomolecules such as van der Waals and hydrophobic interactions are adequate to successfully create a functional biointerface. This review summarizes the various biofunctionalization approaches used in the most common microfluidic substrates: glass and paper. In addition, several biofunctionalization examples are proposed and described in detail along with their associated applications.

Fabrication and Applications of Microfluidic Devices: A Review

“…Unlike for macroscale vessels, the wetting and contact angles of an aqueous solution on the chip materials are of fundamental importance [ 5 ]. Other essential properties that must be considered when choosing the material are durability, ease of fabrication, transparency, biocompatibility, chemical compatibility with the implied reagents, meeting the temperature and pressure conditions needed for the reaction, and the potential of the surface functionalization [ 11 , 23 , 24 ].…”

“…Various kinds of materials attempt to match these properties and can be used for the manufacturing of microfluidic devices [ 10 , 25 ]. Typical substrates include glass, silicon, metals, polymers, and ceramics, but the diversity and quality of materials are continuously increasing [ 6 , 11 , 17 , 24 , 25 ]. Each material has both advantages and disadvantages, depending on its destination use [ 6 ].…”

“…Glass is chemically inert [ 10 , 17 , 28 , 30 ], thermostable [ 10 , 25 , 28 ], electrically insulating [ 2 ], rigid [ 28 ], biologically compatible [ 10 , 17 ], and allows easy surface functionalization [ 24 , 25 , 28 ]. These properties make glass-based microreactors suitable for carrying out chemical reactions that require extreme conditions: high temperatures, high pressures, and aggressive solvents [ 6 , 17 , 24 , 25 ]. The higher resolution at the micrometer scale that is achieved in glass microcapillary reactors compared with other materials makes these devices suitable for the better-controlled synthesis of emulsions and polymeric nanoparticles [ 26 ].…”

“…Glass compatibility with biological samples makes it useful for biochemical analyses [ 17 ]. Hence, it is no surprise that glass is one of the most popular materials for microfluidic chips [ 24 ]. In terms of composition, these substrates are usually made of soda-lime glass, borosilicate glass, and fused quartz [ 10 ].…”

“…Since 2007, paper-based microfluidics has been explored as an alternative to expensive materials for microfluidic applications [ 34 , 39 ]. Paper-based systems benefit from simplicity [ 40 ], accessibility [ 29 ], significant low costs [ 29 , 39 , 40 , 41 ], high porosity [ 2 , 29 ], high physical absorption [ 24 ], ease of manipulation and sterilization [ 29 ], potential for chemical or biological modifications [ 29 ], similarity to the native ECM [ 29 ], bio-affinity [ 24 ], biocompatibility [ 29 ], light weights [ 41 ], and the ability to operate without supporting equipment [ 39 , 41 ]. What makes paper so special is the surface tension of a fluid and its contact angle with cellulose fibers [ 33 ].…”