초록 ▼

Biological assays using various constructions of biochips are disclosed to mirror in vivo situations. The biochip 50 comprises a microchannel 51 having a liquid outlet port 1, bubble release port 2 and a liquid outlet port 3 with an associated bubble release port 4. A multiplicity of tests can be pe

Biological assays using various constructions of biochips are disclosed to mirror in vivo situations. The biochip 50 comprises a microchannel 51 having a liquid outlet port 1, bubble release port 2 and a liquid outlet port 3 with an associated bubble release port 4. A multiplicity of tests can be performed often by coating the bore of the microchannel 50 which various adhesion mediating proteins or the use of chemoattractants. The assay assembly 60 comprises a syringe pump feeding the biochip 50. An inverted microscope 65, digital camera 66 and recorder 67 are provided. A sample liquid containing cells in suspension is injected slowly through the biochip and the effect of the assay recorded over a long period.

대표청구항 ▼

What is claimed is: 1. A biological assay method of assesing cellular adhension comprising: preparing a sample liquid of a suspension of animal cells; coating an internal bore of a biochip with a coating which promotes cellular adhesion, the biochip comprising an elongate enclosed microchannel wit

What is claimed is: 1. A biological assay method of assesing cellular adhension comprising: preparing a sample liquid of a suspension of animal cells; coating an internal bore of a biochip with a coating which promotes cellular adhesion, the biochip comprising an elongate enclosed microchannel with an internal bore; delivering the sample liquid at a controlled steady flow rate through the biochip; and examining the sample liquid over time to observe the effect of the coating on the sample; whereby the adhesion of cells in the sample liquid on the coating of the microchannel is assessed dependent on shear stress or controlled flow rate to which the sample liquid is subjected. 2. The biological assay method according to claim 1 comprising coating the internal bore of the biochip with a protein in the form of an extracellular matrix ligand to study cell attachments. 3. The biological assay method according to claim 1 comprising: coating the internal bore of the biochip by seeding the biochip with endothelial cells; and allowing the cells to grow and form an endothelial layer on the bore to study cell-cell interaction. 4. The biological assay method according to claim 1, wherein the cells are taken from an animal and the bore of the biochip is substantially the same size as the post capillary venules of the animal. 5. The biological assay method according to claim 1, wherein a reagent liquid is delivered simultaneously with the sample liquid through the biochip. 6. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel. 7. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel, the fluid pressure of the liquids being so chosen as to cause a diffusion of the reagent through the interconnecting channel and into the sample liquid. 8. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel, and the fluid pressures of the liquids are maintained equal to prevent diffusion of the reagent through the interconnecting channel. 9. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel having a restricted entry throat. 10. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel having a restricted entry throat, the fluid pressure of the liquids being so chosen as to cause a diffusion of the reagent through the interconnecting channel and into the sample liquid. 11. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel having a restricted entry throat and the fluid pressures of the liquids are maintained equal to prevent diffusion of the reagent through the interconnecting channel. 12. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel having a restricted entry throat having a cross-section less than that of a cell freely suspended in the sample liquid. 13. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel having a restricted entry throat having a cross-section less than that of a cell freely suspended in the sample liquid, the fluid pressure of the liquids being so chosen as to cause a diffusion of the reagent through the interconnecting channel and into the sample liquid. 14. The biological assay method according to claim 1, further comprising delivering a reagent liquid at a controlled steady flow rate through a second microchannel connected to the elongate enclosed microchannel, the microchannels being connected intermediate their ends by an interconnecting channel having a restricted entry throat having a cross-section less than that of a cell freely suspended in the sample liquid and the fluid pressures of the liquids are maintained equal to prevent diffusion of the reagent through the interconnecting channel. 15. The biological assay method according to claim 1, wherein the sample liquid contains more than one cell type in suspension. 16. The biological assay method according to claim 1, further comprising delivering a reagent liquid and the sample liquid through the microchannel to form multilaminar flow. 17. The biological assay method according to claim 1, further comprising: delivering a reagent liquid and a sample liquid through a microchannel to form multilaminar flow, the sample liquid comprising a plurality of cell types in suspension and the reagent liquid comprising a chemoattractant suitable for one of the plurality of cell types; allowing the flow to continue sufficiently so as to remove one of the plurality of cell types into the reagent liquid; and separating the reagent liquid and the sample liquid. 18. The biological assay method according to claim 1, wherein the biochip comprises two microchannels, one a feeding microchannel having a cell reservoir intermediate its ends and the other a reactant microchannel connected to the reservoir by a connecting means comprising: storing cells in the cell reservoir; feeding and growing the cells in the cell reservoir by delivering a culture medium through the feeding microchannel; and delivering reagent liquid through the reactant microchannel. 19. The biological assay method according to claim 1, wherein the biochip comprises two microchannels, one a feeding microchannel having a cell reservoir intermediate its ends and the other a reactant microchannel connected to the reservoir by a connecting means comprising: storing cells in the cell reservoir; feeding and growing the cells in the cell reservoir by delivering a culture medium through the feeding microchannel; and delivering a reagent through the reactant microchannel, wherein said reagent is selected from the group consisting of chemoattractant toxic substance and cell-derived chemoattractant. 20. The biological assay method according to claim 1, wherein a plurality of tests are carried out simultaneously using a sample liquid forming portion of a larger sample and using different test conditions. 21. The biological assay method according to claim 1, wherein a plurality of tests are carried out simultaneously using different sample liquids and the same test conditions. 22. The biological assay method according to claim 1, wherein the internal bore of the biochip is coated with a protein.