Abstract
In this review, we describe different methods of microarray fabrication based on the use of micro-particles/-beads and point out future tendencies in the development of particle-based arrays. First, we consider oligonucleotide bead arrays, where each bead is a carrier of one specific sequence of oligonucleotides. This bead-based array approach, appearing in the late 1990s, enabled high-throughput oligonucleotide analysis and had a large impact on genome research. Furthermore, we consider particle-based peptide array fabrication using combinatorial chemistry. In this approach, particles can directly participate in both the synthesis and the transfer of synthesized combinatorial molecules to a substrate. Subsequently, we describe in more detail the synthesis of peptide arrays with amino acid polymer particles, which imbed the amino acids inside their polymer matrix. By heating these particles, the polymer matrix is transformed into a highly viscous gel, and thereby, imbedded monomers are allowed to participate in the coupling reaction. Finally, we focus on combinatorial laser fusing of particles for the synthesis of high-density peptide arrays. This method combines the advantages of particles and combinatorial lithographic approaches.
Highlights
The necessity of studying a large variety of molecules in a high-throughput manner, mainly triggered by biological research in the early nineteen nineties, has led to the development of different microarray approaches
On which we focus is the use of particles as monomer carriers for the combinatorial synthesis of peptide arrays
Particle-based microarrays have attracted a lot of attention from scientists over the last two decades, due to their enormous potential in high-throughput screening applications
Summary
The necessity of studying a large variety of molecules in a high-throughput manner, mainly triggered by biological research in the early nineteen nineties, has led to the development of different microarray approaches. Due to advances in robotics, the Merrifield synthesis [8,9] was routinely performed on beads, made of cross-linked polystyrene, with a diameter of 200–500 μm This bead-based combinatorial peptide library is synthesized on a large number of beads: in each synthesis cycle, the beads are first split into 20 equal portions. Having a superior diversity generation rate, the split-mix synthesis requires, labor-intensive encoding or decoding to recover the amino acid sequences on those beads showing biological activity. This drawback is overcome by the array approach, where the sequence can be decoded by the position of the molecules. For a detailed description of the modern non-particle methods of peptide array synthesis, we refer to the review of Assaf Friedler [10]
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