Methods and apparatus for detecting the effect of cell affecting agents on living cells

• US 5,496,697 A
• Filed: 09/08/1993
• Issued: 03/05/1996
• Est. Priority Date: 10/21/1988
• Status: Expired due to Fees

• Current Assignee: Molecular Devices
• Original Assignee: Molecular Devices
• Inventors: Kercso, Josef E., McConnell, Harden M., Kercso, Karen M., Owicki, John C., Parce, John W., Humphries, Gillian M. K.
• Primary Examiner(s): Gitomer, Ralph J.
• Application Number:
  US08/118,094
• Time in Patent Office: 909 Days
• Field of Search: 435/5, 435/7.1, 435/29, 435/32, 435/34, 435/817, 435/948
• US Class Current: 435/5
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 35/08 Chemical, biochemical or biological means, e.g. plasma jet, co-culture
• CPC Class Codes: C12M 41/46 of cellular or enzymatic activity or functionality, e.g. cell viability
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

Methods and apparatus are disclosed for detecting the effects of cell affecting agents on living cells. The method steps include providing living cells that are retained in a micro flow chamber. The micro flow chamber is adapted for either continuous or intermittent flow of solutions or suspensions in intimate contact with the cells. The solutions or suspensions, which contain a cell affecting agent, are then flowed in intimate contact with the cells and the pit is measured.

Claims

1. A method for detecting a pH change effect of a cell affecting agent on living cells comprising:

(a) providing living cells retained in a micro flow chamber having a height of about 50 μ

m to about 200 μ

m and having a means for continuous or intermittent flow of a solution or a suspension containing the cell affecting agent in contact with the cells such that the amount of the cell affecting agent in contact with the cells can be controlled;

(b) flowing a solution or suspension containing the cell affecting agent such that it comes into contact with the living cells thereby producing a change in pH of the solution of suspension about said living cells; and

(c) repetitively stopping the flow and repetitively measuring the change in pH of the solution or suspension about said living cells when the flow is stopped, by a means for detecting Ph to detect any change in Ph caused by the cell affecting agent on said living cells.

2. A method for screening for the presence or activity of a drug comprising:

(a) providing a micro flow chamber having a height of between about 50 μ

m and 200 μ

m with a portion of the micro flow chamber being a silicon semiconductor electrode, said micro flow chamber being adapted for continuous or intermittent flow of a solution or a suspension containing a drug to be tested through the micro flow chamber;

(b) further providing living cells responsive to the drug in the micro flow chamber in contact with or in the immediate vicinity of the silicon semiconductor electrode;

(c) contacting the living cells with the drug to be tested by flowing a solution or suspension of the drug to be tested through the micro flow chamber; and

(d) repetitively stopping the flow and repetitively measuring the change in pH of the solution or suspension about said living cells when the flow is stopped by means of the silicon semiconductor electrode to measure any change in pH caused by the drug interacting with the living cells so as to screen for the presence or activity of the drug.

3. A method for detecting a toxic substance comprising:

(a) providing a micro flow chamber having a height of between about 50 μ

m and 200 μ

m and wherein a portion of the micro flow chamber is a silicon semiconductor electrode, the micro flow chamber being adapted for continuous or intermittent flow of a solution or suspension suspected of containing a toxic substance;

(b) further providing living cells responsive to the toxic substance being tested in the micro flow chamber in contact with or in the immediate vicinity of the silicon semiconductor electrode;

(c) contacting the living cells with the solution or suspension suspected of containing the toxic substance by flowing the solution or suspension through the micro flow chamber and; and

(d) repetitively stopping the flow and repetitively measuring the change in pH of the solution or suspension about said living cells when the flow is stopped by means of the silicon semiconductor electrode so as to detect the presence of the toxic substance.