Cell flow apparatus and method for real-time of cellular responses

A method for identifying compounds which produce a cellular response comprising:

• (a) using an automated and computer controlled apparatus to sequentially combine each of a plurality of cell suspensions with one or more test compounds to form each of a plurality of test mixtures;
• (b) sequentially directing each of said plurality of test mixtures through a detection zone, said detection zone being capable of detecting cellular responses in individual cells;
• and
• (c) measuring one or more cellular responses to said one or more test compounds in individual suspended cells as each of said plurality of test mixtures are flowing through said detection zone.

A method of determining whether a sample contains one or more molecules comprising:

• using an automated and computer controlled apparatus to sequentially combine one or more agents capable of binding one or more molecules with each of a plurality of samples to form a plurality of test mixtures;
• sequentially directing each of said plurality of test mixtures through a detection zone;
• and
• determining whether said one or more agents are bound to said one or more molecules as each of said test mixtures are flowing through said detection zone.

A method of determining whether a sample contains one or more polypeptides comprising:

• attaching one or more antibodies which specifically bind said one or more polypeptides to solid supports;
• using an automated and computer controlled apparatus to sequentially combine said one or more antibodies attached to solid supports with samples to form a plurality of test mixtures;
• sequentially directing each of said plurality of test mixtures through a detection zone;
• and
• determining whether said one or more antibodies are bound to said one or more polypeptides as each of test mixtures are flowing through said detection zone.

A method of determining whether a sample contains one or more nulceic acids comprising:

• attaching one or more nucleic acid probes which specifically bind said nucleic acids to solid supports;
• using an automated and computer controlled apparatus to sequentially combine said one or more probes attached to said solid supports with samples to form a plurality test mixtures;
• sequentially directing each of said plurality of test mixtures through a detection zone;
• and
• determining whether said one or more probes are bound to said one or more nucleic acids as each of said test mixtures are flowing through said detection zone.

A method of determining whether a sample contains one or more single nucleotide polymorphisms comprising:

• performing an extension reaction on a each of a plurality of nucleic acid samples using one or more nucleic acid primers for each of said plurality of nucleic acid samples, said one or more nucleic acid primers having a 3′ end immediately adjacent to the polymorphic base of one or more single nucleotide polymorphisms, thereby incorporating one base into said nucleic acid primers;
• attaching the extended primers to solid supports;
• sequentially directing said solid supports having primers attached thereto for each of said plurality of nucleic acid samples through a detection zone in an apparatus;
• and
• determining the identities of the bases incorporated in said extension reaction.

A method of obtaining cells having a desired phenotype or cellular response profile comprising the steps of:

• (a) using an automated and computer controlled apparatus to sequentially combine a each of a plurality of cell suspensions with one or more compounds which produce a cellular response to form a plurality of test mixtures;
• (b) sequentially directing each of said plurality of test mixtures through a detection zone, said detection zone being capable of detecting a plurality of cellular parameters simultaneously;
• (c) simultaneously measuring a plurality of cellular parameters in said suspended cells as each of said plurality of test mixtures are flowing through said detection zone;
• and
• (d) delivering cells having a desired phenotype or cellular response profile into a receptacle.

A method of obtaining cells having a desired phenotype or cellular response profile comprising the steps of:

• (a) using an automated and computer controlled apparatus to sequentially combine a each of a plurality of cell suspensions with one or more compounds which produce a cellular response to form a plurality of test mixtures;
• (b) sequentially directing each of said plurality of test mixtures through a detection zone, said detection zone being capable of detecting cellular responses in individual cells;
• (c) simultaneously measuring a plurality of cellular parameters in said suspended cells as each of said plurality of test mixtures are flowing through said detection zone;
• and
• (d) delivering cells having a desired phenotype or cellular response profile into a receptacle.

An apparatus comprising:

• an automated test compound source capable of sequentially providing each of a plurality of test compounds;
• an automated test substrate source capable of sequentially providing each of a plurality of test compounds;
• a mixing chamber in fluid communication with said test compound source and said test substrate source, wherein said mixing chamber is adapted to combine a test compound received from said test compound source with a test substrate received from said test substrate source to generate a mixture;
• and
• a detector in fluid communication with said mixing chamber, said detector being capable of detecting an interaction between said test compound and said test substrate while said mixture is passing through said detector.

An apparatus comprising:

• one or more automated sample inputs for sequentially providing each of a plurality of samples, said each of said samples comprising one or more test compounds to be evaluated for the ability to produce a cellular response or a solution to be evaluated for the presence of molecules;
• one or more automated cell or particle inputs for sequentially providing each of a plurality of cell suspensions or particles;
• a mixing zone, coupled to said sample input, for receiving the samples, receiving the cell suspension or particles from the cell or particle input and mixing each sample with the cell suspensions or particles;
• and
• a detector which detects one or more signals from a single cell or particle, said detector being coupled to the mixing zone and being capable of measuring one or more cellular responses in the suspended cells or determining whether one or more molecules are present in said samples.