Devices for Analyzing the Presence and Concentration of Multiple Analytes Using a Diffusion-based Chemical Sensor

Abstract

Abstract of Disclosure The present invention provides a microfabricated sensor and a method capable of rapid simultaneous measurement of multiple analytes in a fluid sample. The sensor is inexpensive, disposable and portable, and requires only microliters of sample, a particular advantage with precious fluids such as blood. The sensor utilizes diffusion between layered laminar streams rather than side by side streams. This allows multiple side by side channels for simultaneous detection of multiple analytes. In the sensor, a sample stream and a carrier stream flow in layers, one on top of the other, and one or more reagents are introduced to the bottom of the carrier stream through either a fluid or a solid reagent inlet. The reagent contains reagent particles which, in the presence of the analyte, have a detectable change in a property. The analyte diffuses into the carrier stream where it interacts with reagent particles and is detected by optical, electrochemical or other means.

Claims 
     
       A diffusion based sensor, comprising: a laminar flow channel having an upstream end and a downstream end; 
       a sample inlet connected to said laminar flow channel for conducting a sample fluid stream into said laminar flow channel;a carrier inlet connected to said laminar flow channel for conducting a carrier fluid stream into said laminar flow channel in layered laminar flow contact with said sample fluid; 
       a first reagent inlet connecting with said laminar channel downstream from said carrier inlet for introducing a reagent into said laminar flow channel in contact with said carrier fluid stream. 
     
     
       The sensor of  claim 1  wherein said first reagent inlet is a reagent stream inlet for conducting a first reagent stream into said laminar flow channel in layered laminar flow contact with said carrier stream. 
     
     
       The sensor of  claim 1  wherein said first reagent inlet is a solid reagent inlet. 
     
     
       The sensor of  claim 3  wherein said solid reagent inlet is a cavity within said flow channel positioned to allow solid reagent to diffuse into said carrier stream. 
     
     
       The sensor of  claim 1  also comprising an outlet connected to said laminar flow channel downstream from said inlets. 
     
     
       The sensor of  claim 1  not comprising an outlet to said laminar flow channel. 
     
     
       The sensor of  claim 1  comprising an absorbent material within said laminar flow channel downstream from said inlets. 
     
     
       The sensor of  claim 1  further comprising a second reagent inlet connected to said laminar flow channel downstream from said carrier inlet for introducing a second reagent into said laminar flow channel in contact with said carrier fluid stream. 
     
     
       The sensor of  claim 8  wherein said second reagent inlet is positioned downstream from said first reagent inlet. 
     
     
       The sensor of  claim 8  further comprising a third reagent inlet connected to said laminar flow channel downstream from said carrier inlet for introducing a third reagent into said laminar flow channel in contact with said carrier fluid stream. 
     
     
       The sensor of  claim 10  wherein said third reagent inlet is positioned downstream from said second reagent inlet. 
     
     
       The sensor of  claim 1  comprising a plurality of reagent inlets connected to said laminar flow channel downstream from said carrier inlet for introducing second and subsequent reagents into said laminar flow channel in contact with said carrier fluid stream, said reagent inlets being positioned in parallel with each other. 
     
     
       The sensor of  claim 12  also comprising multiple detectors positioned with respect to said channel to detect interaction of components of said sample stream with said reagents. 
     
     
       The sensor of  claim 1  comprising a plurality of reagent inlets connected to said laminar flow channel downstream from said carrier inlet for introducing second and subsequent reagents into said laminar flow channel in contact with said carrier fluid stream, said reagent inlets being positioned in series with each other. 
     
     
       The sensor of  claim 14  also comprising multiple detectors positioned with respect to said channel to detect interaction of components of said sample stream with said reagents. 
     
     
       The sensor of  claim 1  wherein said channel is enlarged at said carrier inlet to accommodate the carrier stream layer. 
     
     
       The sensor of  claim 1  wherein said channel is a convoluted channel. 
     
     
       The sensor of  claim 1  wherein the length of said channel is between about 5 mm and 50 mm. 
     
     
       The sensor of  claim 1  wherein said sample inlet is preceded by a filter. 
     
     
       The sensor of  claim 19  wherein said filter is a diffusion based microfilter. 
     
     
       The sensor of  claim 1  for use with optical detection wherein at least a portion of said channel is formed in a transparent material. 
     
     
       The sensor of  claim 1  for use with electrochemical detection further comprising an electrode positioned in said channel downstream from said reagent inlet. 
     
     
       The sensor of  claim 22  further comprising one or more additional electrodes positioned in said channel downstream from said reagent inlet. 
     
     
       The sensor of  claim 23  wherein said electrodes are positioned in series. 
     
     
       The sensor of  claim 22  wherein said electrode is deposited on the surface of said channel. 
     
     
       The sensor of  claim 1  for use with both electrochemical and optical detection, wherein at least a portion of said channel is formed in a transparent material, and wherein said channel comprises an electrode positioned in said channel downstream from said reagent inlet.