Method for combinatorial particle manipulation for producing high-density molecule arrays, in particular peptide arrays, and molecule arrays that can be obtained by means thereof
The present invention relates to a method for combinatorial particle manipulation for producing high-density molecule arrays, and to the high-density molecule arrays obtained therefrom. In particular, the present invention relates to a method for producing high-density molecule arrays, in particular peptide or oligonucleotide arrays, by combinatorial patterning of particles, wherein the patterning is achieved by the selective and direct action of electromagnetic radiation.
1. A method for producing high-density molecule arrays having a pitch of 300 μm or less, the method comprising:
(i) providing a target substrate having a plurality of discrete spots,
(ii) conditioning selected spots of the target substrate by electromagnetic radiation, and
(iii) reacting at least one monomer with reactants present in immobilized form in the selected spots of the target substrate,
wherein there is provided at least one starting substrate having a film layer in which the at least one monomer is present, wherein step (ii) of conditioning selected spots comprises a selective transfer of material of the at least one monomer from the starting substrate to the target substrate and a site-specific fixing of the material to the target substrate, wherein the selective transfer and/or the site-specific fixing is by electromagnetic radiation which comprises laser light,
wherein at least one intermediate layer which assists the transfer of material is arranged between the starting substrate and the film layer,
wherein the selected transfer and the site-specific fixing of the material from the starting substrate to the target substrate is without direct contact between the substrates, and wherein the material is transferred in liquid or gaseous form.
2. The method of claim 1 , wherein the selective transfer of material from the starting substrate and the site-specific fixing to the target substrate by contacting the starting substrate with the target substrate and heating or the film layer directly or indirectly by the electromagnetic radiation, wherein the material layer is situated between the starting substrate and the target substrate.
3. The method of claim 2 , wherein the starting substrate and/or the target substrate comprises a flexible material.
4. The method of claim 2 , wherein the starting substrate and/or the target substrate is exposed to vibrations or excited to mechanical oscillations during the contacting.
5. The method of claim 1 , wherein the transfer of the material is by one or more of the mechanisms comprising ablation, detachment of the material by a pulse transmitted by photons, optical tweezers principle, generation of an electric field between the substrates and generation of a magnetic field between the substrates.
6. The method of claim 5 , wherein the site-specific fixing of the transferred material to the target substrate is by direct or indirect heating of the material.
7. The method of claim 5 , wherein the selective transfer of material is by expansion of the volume of the film layer, or wherein one or more intermediate layers which assist the transfer of material is arranged between the starting substrate and the material layer, and the selective transfer of material is by expansion of the volume of the at least one intermediate layer.
8. The method of claim 7 , wherein the selective transfer of material is by the formation of a bubble in the film layer or the at least one intermediate layer.
9. The method of claim 1 , wherein steps (ii) and (iii) are carried out iteratively with identical or different starting substrates.
10. The method of claim 1 , wherein a space between the substrates and/or between monomer particles is filled with a liquid.