Biomolecule Patterning on Analytical Devices: A Microfabrication-Compatible Approach

Abstract

The present work describes a methodology for patterning biomolecules on silicon-based analytical devices that reconciles 3-D biological functionalization with standard resist lift-off techniques. Unlike classic sol-gel approaches in which the biomolecule of interest is introduced within the sol mixture, a two-stage scenario has been developed. It consists first of patterning micrometer/submicrometer polycondensate scaffold structures, using classic microfabrication tools, that are then loaded with native biomolecules via a second simple incubation step under biologically friendly environmental conditions. The common compatibility issue between the biological and microfabrication worlds has been circumvented because native recognition biomolecules can be introduced into the host scaffold downstream from all compatibility issues. The scaffold can be generated on any silicon substrate via the polycondensation of aminosilane, namely, aminopropyltriethoxy silane (APTES), under conditions that are fully compatible with resist mask lithography. The scaffold porosity and high primary amine content allow proteins and nucleic acid sequences to penetrate the polycondensate and to interact strongly, thus giving rise to micrometer/submicrometer 3-D structures exhibiting high biological activity. The integration of such a biopatterning approach in the microfabrication process of silicon analytical devices has been demonstrated via the successful completion of immunoassays and nucleic acid assays.

Chemically Treated 3D Printed Polymer Scaffolds for Biomineral Formation

“…This is due to the difficulty the adherent cells experience with more hydrophobic surfaces; however, the relatively high water contact angle of the APTES sample appears to be contrary to this trend. This is most likely due to the alkoxysilane contributing to its hydrophobicity but also providing a highly porous primary amine-rich network providing an ideal substrate for strong protein interaction, 39 leading to good cell adhesion and growth.…”

“…Silanization of surfaces with monolayers , and 3D porous networks has been shown to increase cell adhesion and activity, with various sol–gel and porous bioglass substrates based on titania and silica been shown to increase growth, proliferation, osteoblast differentiation, and bone formation. , These factors can also be affected by the nanoporosity of bioglass, addition of hydroxyapatite nanoparticles, and repeated heating . Similarly, the addition of magnetic nanoparticles to a polymer deposition 3D printed system has been shown to increase proliferation and osteogenesis-related gene expression .…”

Multiscattering-enhanced optical biosensor: multiplexed, non-invasive and continuous measurements of cellular processes

“…Currently, mainly electrochemical biosensors are used for the extracellular detection of both glucose and lactate. Large efforts have been put into the design of those sensors, especially structuring the electrodes with mediators, gels, polymeric matrices and various nanomaterials [18][19][20][21][22][23][24][25][26][27]. Most reported methods are based on sample collection prior to laboratory analysis and are, therefore, end-point assays [28,29].…”

Selective patterning of Si-based biosensor surfaces using isotropic silicon etchants

“…As biosensor platforms become increasingly involved, for instance, via multiplexing capabilities, the need to further refine these targeting strategies by performing selective patterning of probe molecules onto the transducer surface becomes paramount [13–16]. Selective patterning’s advantage is that it allows for highly targeted detection, increasing sensitivity by eliminating possible signal shifts in optical devices due to residual probe molecules [14–16].…”

“…Selective patterning’s advantage is that it allows for highly targeted detection, increasing sensitivity by eliminating possible signal shifts in optical devices due to residual probe molecules [14–16]. For many applications, patterning may be accomplished by spotting the surface using ink-jet or microcontact printing to less than 100 nm resolution [17], but this method can potentially damage the underlying sensing device, particularly if that surface is patterned with small-scale features [18].…”