Biochip assembly and assay method thereof

Abstract

The present invention is directed to a biochip assembly comprising a semi-permeable membrane and an assay method using said biochip assembly for carrying out cell based assays. Ideally, such a method involves measuring the migration of cells in a channel under the influence of an analyte wherein said cells are separated from said analyte by a semi-permeable membrane and said analyte and/or said cells are subjected to controlled flow conditions.

1 . A method for measuring the migration of cells in a channel under the influence of an analyte wherein said cells are separated from said analyte by a semi-permeable membrane and said analyte and/or said cells are subjected to controlled flow conditions. 
     
     
         2 . The method of  claim 1  wherein the method takes place in an elongate enclosed channel having a semi-permeable membrane mounted therein. 
     
     
         3 . The method of  claim 1  wherein said cells are present on at least one side of said semi-permeable membrane and said analyte is present on the opposed surface thereto. 
     
     
         4 . The method of  claim 1  wherein said sample cells and/or said analyte are introduced into the channel at a controlled steady flow rate. 
     
     
         5 . The method of  claim 1  wherein said cells or said analyte on one side of said membrane is subjected to controlled flow. 
     
     
         6 . The method of  claim 1  wherein said cells or said analyte on both sides of said membrane are subjected to controlled flow. 
     
     
         7 . The method of  claim 1  wherein said channel is a microchannel. 
     
     
         8 . The method of  claim 1  wherein said analyte is a reagent liquid or gel or a reagent eluting cell. 
     
     
         9 . The method of  claim 1  further comprising forming a layer of seeded cells adjacent to at least one side of said semi-permeable membrane. 
     
     
         10 . The method of  claim 9  wherein said layer of seeded cells is formed and mounted in the channel prior to use. 
     
     
         11 . The method of  claim 1  further comprising coating at least one side of the semi-permeable membrane with one or more substances which effect cell function prior to forming a layer of seeded cells on said semi-permeable membrane. 
     
     
         12 . The method of  claim 11  wherein the substance promotes adhesion of cells. 
     
     
         13 . The method of  claim 11  wherein the substance is in the form of a gel. 
     
     
         14 . The method of  claim 9  wherein the seeded cells form either a confluent or non-confluent layer adjacent to said semi-permeable membrane. 
     
     
         15 . The method of  claim 9  wherein the interaction between said seeded cells and said sample cells is monitored and/or recorded. 
     
     
         16 . The method of  claim 1  comprising a further step of
 coating the internal bore of the channel prior to use with a substance which interacts with said seeded and/or sample cells, preferably a cell adhesion molecule and/or a cell transmigration substance. 
 
     
     
         17 . The method of  claim 16  wherein the physiological function of said seeded cells is monitored and/or recorded. 
     
     
         18 . The method of  claim 9  wherein the physiological function of said seeded cells is measured as a function of the shear stress within the channel. 
     
     
         19 . The method of  claim 1  comprising introducing analyte to said channel and monitoring and/or recording the response of said seeded cells and/or sample cells to said analyte, in terms of adsorption, metabolism and/or toxicity. 
     
     
         20 . The method of  claim 1  or  claim 9  wherein cell to cell interactions and cell to analyte interactions are measured. 
     
     
         21 . The method of  claim 1  wherein the flow is sustained by a pressure driven pumping system or a positive displacement pumping system. 
     
     
         22 . A biochip assembly for carrying out assays with living cells wherein the assembly comprises at least one elongate enclosed channel having a semi-permeable membrane mounted therein. 
     
     
         23 . The biochip assembly of  claim 22  comprising a plurality of elongate enclosed channels. 
     
     
         24 . The biochip assembly according to  claim 22  for carrying out assays with living cells wherein the assembly comprises at least one elongate enclosed channel having a semi-permeable membrane mounted therein wherein the semi-permeable membrane acts as a divider wall separating the elongate enclosed channel into a first channel and a second channel 
     
     
         25 . The biochip assembly of  claim 24  wherein the first channel receives sample cells and the second channel receives analyte or vice versa. 
     
     
         26 . A biochip assembly for carrying out assays with living cells wherein the assembly comprises at least one elongate enclosed channel having a semi-permeable membrane mounted therein wherein the semi-permeable membrane forms a connecting wall between at least two adjoining channels. 
     
     
         27 . The assembly of  claim 26  comprising a first and second channel wherein the first channel receives said sample cells and the second channel receives said analyte. 
     
     
         28 . The assembly of  claim 26  wherein the adjoining channels are in line. 
     
     
         29 . The assembly of  claim 26  in which the adjoining channels intersect at one section only. 
     
     
         30 . The assembly of  claim 24  wherein the semi-permeable membrane abuts the elongate enclosed channel. 
     
     
         31 . The assembly of  claim 24  wherein the semi-permeable membrane permits unidirectional or bidirectional flow. 
     
     
         32 . The assembly of  claim 24  wherein part of the channel is in contact with said semi-permeable membrane. 
     
     
         33 . The assembly of  claim 24  wherein said semi-permeable membrane comprises one or more semi-permeable membrane types characterized by different membrane properties. 
     
     
         34 . The assembly of  claim 33  wherein each semi-permeable membrane type has different pore size and/or different membrane size. 
     
     
         35 . The assembly of  claim 24  wherein at least one surface of the cell transparent membrane comprises one or more substances which effect cell function, preferably a substance which promotes the adhesion of cells. 
     
     
         36 . The assembly of  claim 24  wherein the semi-permeable membrane is a cell transparent membrane. 
     
     
         37 . The assembly of  claim 37  wherein the cell transparent membrane is seeded with cells. 
     
     
         38 . The assembly of  claim 37  wherein the cell transparent membrane is selectively permeable to different cell types. 
     
     
         39 . A biochip assembly for carrying out assays with living cells wherein the assembly comprises at least one elongate enclosed channel and a well wherein a semi-permeable membrane separates said channel from said well.