Microfluidic particle-analysis systems

Abstract

The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or detection of particles, such as cells and/or beads. The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or analysis of particles, such as cells, viruses, organelles, beads, and/or vesicles. The invention also provides microfluidic mechanisms for carrying out these manipulations and analyses. These mechanisms may enable controlled input, movement/positioning, retention/localization, treatment, measurement, release, and/or output of particles. Furthermore, these mechanisms may be combined in any suitable order and/or employed for any suitable number of times within a system. Accordingly, these combinations may allow particles to be sorted, cultured, mixed, treated, and/or assayed, among others, as single particles, mixed groups of particles, arrays of particles, heterogeneous particle sets, and/or homogeneous particle sets, among others, in series and/or in parallel. In addition, these combinations may enable microfluidic systems to be reused. Furthermore, these combinations may allow the response of particles to treatment to be measured on a shorter time scale than was previously possible. Therefore, systems of the invention may allow a broad range of cell and particle assays, such as drug screens, cell characterizations, research studies, and/or clinical analyses, among others, to be scaled down to microfluidic size. Such scaled-down assays may use less sample and reagent, may be less labor intensive, and/or may be more informative than comparable macrofluidic assays.

What is claimed is:  
     
         1 . A microfluidic device for exposing cells to a plurality of compounds comprising: 
 (a) a cell inlet;    (b) a plurality of cell chambers, each in fluidic communication with each other and said cell inlet;    (c) a plurality of chamber isolation valves, said isolation valves, when actuated, fluidicly isolating said chambers from each other;    (d) a plurality of compound inlets and outlets, each compound inlet and outlet being in fluid communication with one of said chambers, said compound inlets and outlets further comprising a cell retention sieve for retaining cells within said chambers while permitting fluid flow through said chambers so that said cells are perfused with said fluid when said fluid is flowed through said chambers from said compound inlets towards said compound outlets, said compound inlets being selectively in fluid communication with a plurality of compound sources, and said compound outlet being in fluid communication selectively either with a common waste receptacle or a common reagent reservoir;    (e) a plurality of compound valves in communication with said compound inlets and outlets, said valves being capable fluidicly isolating said chamber from said compound sources and said common receptacle and common reagent reservoir;    (f) a common waste receptacle valve, said common waste receptacle valve being capable of fluidicly isolating said common waste receptacle from said chamber when actuated; and, (g) a common reagent reservoir valve, said common reagent reservoir valve being capable of fluidicly isolating said common waste receptable from said chamber when actuated.    
     
     
         2 . The device of  claim 1  wherein at least one of said plurality of compounds is a cell toxic compound.  
     
     
         3 . The device of  claim 1  wherein said common reagent reservoir contains a detection agent responsive to a toxic response of said cells to one of said compounds.  
     
     
         4 . A method for determining whether one of a plurality of compounds causes a toxic response in one of a plurality of cells comprising the steps of: 
 providing the device of  claim 1;     introducing said cells into said device of  claim 1 ,    isolating said cells within said chambers of said device of  claim 1 ,    exposing said cells to said plurality of said compounds while said cells are retained in said chambers,    determining whether any of said cells had a toxic response resulting from exposure to one of said plurality of compounds.