Devices capable of fluid sample concentration for extended sensing of analytes

Abstract

The disclosed invention provides a fluid sensing device and method capable of collecting a fluid sample, concentrating the sample with respect to one or more target analytes, and measuring the target analyte(s) in the concentrated sample. The invention is also capable of determining the change in molarity of the fluid sample with respect to the target analyte(s), as the sample is concentrated by the device. The invention further includes a method for using a fluid sensing device to concentrate a fluid sample with respect to one or more target analytes. The disclosed method further includes the ability to correlate the measured target analyte concentration to a physiological condition of a device wearer, or of a fluid source.

What is claimed is: 
     
         1 . A sweat sensing device capable of sample concentration and configured to be placed on a device wearer's skin, comprising:
 at least one first analyte-specific sensor for measuring a first analyte in a concentrated sweat sample;   at least one sweat collector that collects an unconcentrated sweat sample from skin, where the unconcentrated sweat sample contains the first analyte at a first molarity; and   at least one sample concentrator receiving the unconcentrated sweat sample from the sweat collector, where the sample concentrator concentrates the sweat sample, so that the concentrated sweat sample contains the first analyte at a second molarity that is at least 2 times higher than the first molarity.   
     
     
         2 . The device of  claim 1  including at least one sweat stimulation component. 
     
     
         3 . The device of  claim 1  where the sample concentrator includes a membrane that is permeable to water but impermeable to the first analyte, and where the membrane has a first side adjacent to a sweat sample and a second side opposite the sweat sample. 
     
     
         4 . The device of  claim 1 , further comprising:
 at least one second analyte-specific sensor for measuring a second analyte in the concentrated sweat sample;   where the unconcentrated sweat sample contains the second analyte at a third molarity; and   where the sample concentrator concentrates the sweat sample, so that the concentrated sweat sample contains the second analyte at a fourth molarity that is at least 2 times higher than the third molarity.   
     
     
         5 . The device of  claim 4  where the ratio of the first molarity to the second molarity is the same as the ratio of the third molarity to the fourth molarity. 
     
     
         6 . The device of  claim 1  where a plurality of the first analyte-specific sensors includes at least one sensor that measures the first analyte in a concentrated sweat sample; and at least one sensor that measures the first analyte in an unconcentrated sweat sample. 
     
     
         7 . The device of  claim 1  where the sample concentrator includes at least one gas-filled pathway that is permeable to evaporated water but impermeable to the first analyte, and where the gap has a first side adjacent to a sweat sample and a second side opposite the sweat sample. 
     
     
         8 . The device of  claim 1 , including at least one sensor for providing a volumetric measurement of a sweat sample. 
     
     
         9 . The device of  claim 1 , including at least one microfluidic gate. 
     
     
         10 . The device of  claim 7 , including at least one desiccant on the second side of the gas-filled pathway. 
     
     
         11 . The device of  claim 7 , including at least one heating component to promote evaporation of water. 
     
     
         12 . The device of  claim 1 , including at least one component capable of creating a reversible flow of a sweat sample. 
     
     
         13 . The device of  claim 12 , where the reversible-flow component includes the application of a voltage gradient. 
     
     
         14 . The device of  claim 1 , including at least one component capable of applying a non-equilibrium pressure to a sweat sample to reverse the flow of the sweat sample. 
     
     
         15 . The device of  claim 1 , where the first analyte-specific sensor is surrounded by an immiscible material which has a distribution coefficient with respect to water or sweat that is greater than 2 for the first analyte. 
     
     
         16 . The device of  claim 9 , where said microfluidic gate controls the flow of a sweat to the first analyte-specific sensor. 
     
     
         17 . The device of  claim 1 , including at least one flow sensor. 
     
     
         18 . The device of  claim 1 , where the device includes a first first-analyte specific sensor and a second first analyte-specific sensor, where the second sensor has a dynamic range of detection that is centered on a higher concentration than for the first sensor. 
     
     
         19 . The device of  claim 3 , including at least one draw material on the second side of the membrane. 
     
     
         20 . The device of  claim 19 , where the draw material contains at least one solute found in sweat, where the solute has a draw material molarity that is at least 2 times greater than a sweat molarity, where the sweat molarity is a concentration of the solute as it is typically found in sweat. 
     
     
         21 . The device of  claim 20 , including at least one analyte-specific sensor for said solute. 
     
     
         22 . The device of  claim 1 , including at least one tunable valve. 
     
     
         23 . The device of  claim 22 , where said tunable valve is in contact with a fluid that is not sweat. 
     
     
         24 . The device of  claim 1 , including at least one channel for transporting a sweat sample that reduces the sample's flow deceleration due to a volume of water that passes into the sample concentrator. 
     
     
         25 . The device of  claim 1 , including at least one of the following: a plurality of sweat stimulation components, and a plurality of reverse iontophoresis components. 
     
     
         26 . The device of  claim 1 , including at least one wicking component, and where the sample concentrator has an osmotic pressure that is at least one of more than 2 times greater than a wicking pressure of the wicking component; and more than 10 times greater than a wicking pressure of the wicking component. 
     
     
         27 . The device of  claim 26 , where the wicking component and the sweat collector are at least partially the same component. 
     
     
         28 . The device of  claim 19 , where the draw material includes a wicking material. 
     
     
         29 . The device of  claim 19 , where the draw material is a polyelectrolyte. 
     
     
         30 . The device of  claim 19 , where the draw material has a volume that is greater than the volume of the total sweat sample volume collected by the device, by at least one of the following: 2 times; 10 times; 100 times; and 1000 times. 
     
     
         31 . The device of  claim 1 , including at least one sensor which measures the total osmolality of the sweat sample. 
     
     
         32 . The device of  claim 19 , including at least one sensor which measures the total osmolality of the draw material. 
     
     
         33 . The device of  claim 1 , where concentrated sweat sample contains the first analyte at a second molarity that is one of the following: at least 2 times higher than the first molarity; at least 10 times higher than the first molarity; and at least 100 times higher than the first molarity; and at least 1000 times higher than the first molarity. 
     
     
         34 . The device of  claim 1 , where the sample concentrator is a microfluidic concentrator channel of known length, and includes a plurality of first analyte-specific sensors that are placed at known intervals within the channel. 
     
     
         35 . The device of  claim 1 , where the sample concentrator is a concentrator channel, where the concentrator channel includes a functionalized surface configured to interact with the first analyte. 
     
     
         36 . The device of  claim 35 , where the sample concentrator is configured to interact with a plurality of target analytes. 
     
     
         37 . The device of  claim 35 , including a plurality of first analyte-specific sensors that are placed at known intervals within the channel 
     
     
         38 . The device of  claim 35 , where the functionalized surface includes one of the following: a functionalized silica gel, a plurality of functionalized beads, or a plurality of functionalized silicon dioxide nanoparticles. 
     
     
         39 . The device of  claim 35 , where the device is configured to cause the first analyte to release from the functionalized surface. 
     
     
         40 . The device of  claim 39 , where the first analyte is released by one of the following: introducing a solvent into the sweat sample; changing the sweat sample pH; changing the sweat sample temperature; or introducing electromagnetic radiation to the sweat sample. 
     
     
         41 . The device of  claim 35 , where the concentrator channel includes a medium having an increasing density gradient oriented in the direction of sweat sample flow through the channel. 
     
     
         42 . The device of  claim 35 , where the concentrator channel includes a medium having a plurality of different densities that create a stepped increasing density gradient oriented in the direction of sweat sample flow through the channel. 
     
     
         43 . The device of  claim 35 , where the concentrator channel includes a medium with pores configured to interact with the first analyte as the sweat sample flows through the channel. 
     
     
         44 . The device of  claim 35 , where the concentrator channel further includes:
 a plurality of capture beads; and   a heating element.   
     
     
         45 . A method of using a sweat sensing device configured to be placed on a device wearer's skin, and capable of sweat sample concentration, comprising:
 placing the device on a wearer;   receiving an unconcentrated sweat sample from the wearer's skin;   concentrating the sweat sample with respect to at least one target analyte;   measuring the target analyte in the sweat sample with an analyte-specific sensor; and   correlating the measurement with a physiological condition of the wearer.   
     
     
         46 . The method of  claim 45 , further including using a sweat stimulation component to stimulate sweat from the wearer's skin. 
     
     
         47 . The method of  claim 45 , where the analyte-specific sensor does not receive the sweat sample until one of the following events occurs: at least one secondary sensor provides an input; a scheduled time; and a device user provides an input. 
     
     
         48 . The method of  claim 45 , further including using at least one flow sensor to determine the degree of concentration of the sweat sample with respect to the target analyte. 
     
     
         49 . The method of  claim 45 , further including:
 using at least one analyte-specific sensor to measure a reference analyte in the sweat sample;   concentrating the sweat sample with respect to the reference analyte, where the reference analyte is concentrated to a similar degree as the target analyte; and   comparing the target analyte measurement to the reference analyte measurement.   
     
     
         50 . The method of  claim 45 , further including: using a tunable valve to control the degree of sweat sample concentration with respect to the target analyte. 
     
     
         51 . The method of  claim 45 , further including:
 using at least one analyte-specific sensor to measure a target analyte in a sweat sample that is unconcentrated with respect to the target analyte;   using at least one analyte-specific sensor to measure the target analyte in a sweat sample that is concentrated with respect to the target analyte;   comparing the unconcentrated target analyte measurement to the concentrated target analyte measurement; and   determining a flow rate for the sweat sample.   
     
     
         52 . The method of  claim 45 , where the sweat sample is concentrated at least 2 times with respect to at least one target analyte; at least 10 times with respect to at least one target analyte; at least 100 times with respect to at least one target analyte; or at least 1000 times with respect to at least one target analyte; 
     
     
         53 . The method of  claim 45 , where the device includes a microfluidic channel of known length, and a plurality of analyte-specific sensors for measuring a target analyte that are placed at known intervals within the channel, further comprising:
 measuring the difference in target analyte concentration between successive sensors;   determining the target analyte concentration increase per unit length of channel; and   determining the total amount of target analyte concentration at each sensor.   
     
     
         54 . The method of  claim 45 , where the device includes a concentrator channel configured to interact with at least one target analyte, further comprising:
 flowing a sweat sample through the channel;   concentrating the at least one target analyte in the sweat sample; and   measuring the concentration of the at least one target analyte.