Abstract:
Embodiments of the present invention are directed to resonating detection devices in which the sample flows through a conduit having a section in which the conduit is grouped or concentrated with the point of maximum movement.

Description:
RELATED APPLICATIONS 
       [0001]    This application claims priority to U.S. Provisional Patent Application Ser. No. 61/089,203, filed Aug. 15, 2008, the entire contents of which are incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    Embodiments of the present invention relate to resonating cantilever arms for measuring changes in mass related parameters. 
       FEDERAL SPONSORSHIP 
       [0003]    This invention was not developed with Federal sponsorship. 
       BACKGROUND OF THE INVENTION 
       [0004]    Embodiments of the present invention are directed devices which induce movement in cantilevered arms. Such devices measure changes in resonance of such arms upon changes in mass. These changes in resonance are used to determine mass related parameters. As used herein, the term “mass related parameters” refers to values which can be measured or calculated from such changes in resonance in cantilevered arms induced or caused by a change in the mass carried by such arm. 
         [0005]    Embodiments of the present invention have particular applications in measuring fluids contained or flowing in microfluidic devices. As used herein, the term “microfluidic” refers to devices which contain approximately 10 micro-liters or less. 
         [0006]    As used herein, the term “analyte” refers to a compound or composition which is of interest. By way of example, without limitation, such analyte can be a compound for which information as to its presence or absence is desired, or its concentration, or the mass of the compound in the solution in which it is dissolved. 
         [0007]    As used herein, the term “solute” refers to a compound that is dissolved. The compound or mixture of compounds in which the solute is dissolved is the solvent. 
         [0008]    Chromatography is a technique in which compounds held in solution are separated from each other by the different affinity such compounds exhibit to a media held stationary or moving in a different manner than the solution in which the compounds are held. High performance liquid chromatography (HPLC) uses pressure to compel solutions carrying compounds of interest through an immobilized media of packed particles or functional equivalent or a monolith plug of porous material. The immobilized media is often referred to as the stationary phase. A compound which exhibits affinity for a stationary phase will leave the stationary phase, and elute, as a concentration of the compound in the solution. Detectors of the compound measure the concentration as a peak. Chromatographic systems are known in the art and generally comprise a pump, sample injector and detectors. Such systems are available from several vendors. 
         [0009]    Presently, there is a need for devices and methods that will provide a analytical value relating to mass of a compound that can be used with separations techniques such as chromatography. 
       SUMMARY OF THE INVENTION 
       [0010]    Embodiments of the present invention feature devices and methods that will provide an analytical value relating to mass of a compound. The devices and methods of the present invention are well suited for use in conjunction with other analytical techniques such as chromatography. One embodiment of the present invention features a device for performing an analysis of a solution. The device has a primary conduit having a first fixed end, second fixed end, at least one first flex section, at least one second flex section and at least one analysis section. The first fixed end and the second fixed end are each for attachment to a base. The first flex section has a first flex section length and, similarly, the second flex section has a second flex section length. The first flex section and the second flex section define a motion point distal to the first end and said second end in which the primary conduit has the greatest degree of motion. The motion point is for vibrating at a resonant frequency determined by the mass of the primary conduit and solutions carried with the primary conduit. The primary conduit has a first channel defining a fluid path for receiving said solutions. The first channel has an inlet, and an outlet. The first inlet is at the first fixed end and the first outlet is at the second fixed end. The first analysis section has at least one curve about the motion point and has an analysis length. The analysis length exceeds at least one half of one of the first flex section length and the second flex section length. The first conduit is for cooperating with means for inducing vibration and means for determining a resonant frequency to calculate a mass related parameter of the solution carried therein. 
         [0011]    The analysis section focuses the mass of solutions carried in the channel to the motion point providing increased sensitivity to changes in the solution mass. 
         [0012]    One embodiment of the present invention features a primary conduit having a first arm. The first arm has a first length, first distal end, and a first proximal end. The length is the distance between the first proximal end and the first distal end. The first proximal end is attached or constructed and arranged to attach to a base. The first distal end is free for vibrating at a resonant frequency determined by the mass of the primary conduit and solutions carried therein. The analytical section of the first channel concentrates or gathers the first channel at the distal end of the arm to increase sensitivity of the arm to changes in mass caused by different concentrations of solute in the solutions. 
         [0013]    One preferred device has an analysis section in the form of a coil or serpentine pattern. Preferably, the coil or serpentine pattern is substantially aligned with the motion point. This alignment places a large volume of fluid potentially containing an analyte in the channel where the device is most sensitive to changes in mass. Embodiments featuring a arm place the coil or serpentine pattern close or at the most distal end. Preferably, the coil or serpentine pattern is placed within the last twenty five percent of the arm. 
         [0014]    One preferred device further comprises energy means for inducing vibration in the first arm. As used herein, “energy means for inducing vibration” comprise mechanical, electrical, optical, acoustic, and magnetic mechanisms for imparting kinetic energy to the primary conduit setting the primary conduit in motion. The primary conduit, in response to the periodic application of such energy, will exhibit a resonant frequency in which the energy to induce and maintain such motion is most efficient. The means for inducing vibration in the primary conduit is, preferably, capable of being placed or is placed in signal communication with determining means for determining a resonant frequency of the primary conduit. 
         [0015]    A preferred device further comprises determining means for determining the resonant frequency of the primary conduit. The determining means for determining the resonant frequency is preferably in signal communication with the energy means for inducing vibration in the primary conduit. For example, without limitation, the determining means monitors and/or controls the phase difference between the energy means and the determining means. Thus, determining means comprises sensors for detecting the movement of the first arm and/or energy consumption of the energy means, and computational processing units (CPUs) for processing the signals and data. A preferred determining means compares the resonant frequency or the energy consumption of the primary conduit in the presence or potential presence of an analyte and compares the value to a standard. The comparison relates to the density and/or mass of one or more solutions flowing through the first channel. 
         [0016]    One preferred device features a primary conduit as described and further comprises a secondary conduit. The secondary conduit is in fluid communication with the primary conduit. The secondary conduit has a secondary first fixed end, a secondary second fixed end, at least one secondary first flex section and at least one secondary second flex section. The secondary first fixed end and the secondary second fixed end are each for attachment to a base. The secondary flex section has a secondary flex section length and, similarly, the secondary second flex section has a secondary second flex section length. The secondary first flex section and secondary second flex section define a secondary motion point distal to the secondary first end and the secondary second end in which the secondary conduit has the greatest degree of motion. The motion point is for vibrating at a resonant frequency determined by the mass of the secondary conduit and solutions carried with the secondary conduit. The secondary conduit has a secondary channel defining a fluid path for receiving the solutions. The secondary channel has a secondary inlet, a secondary outlet, and at least one secondary analysis section. The first inlet is at the secondary first fixed end and the first outlet at the secondary second fixed end. The secondary analysis section spans therebetween and defines a secondary channel volume. The second channel volume is smaller than the volume of the primary analysis section to allow measurement of mass parameters of a solution in the presence and absence of a peak in the first channel and the second channel. 
         [0017]    Preferrably, the second conduit allows measurement of at least one mass parameter of a solution in which the analyte is the present in at least one of the first channel and second channel and absent in the other. Thus, the difference in mass of the analyte can be directly related to the differences in resonance of the primary conduit. 
         [0018]    Preferably, the embodiments further comprise energy means for inducing vibration in said second arm and further determining means for determining the resonant frequency of said second arm. Preferably, such determining means determines a mass change related to the presence of an analyte in accordance with the equation: 
         [0000]    
       
         
           
             
               
                 δω 
                 0 
               
               
                 ω 
                 0 
               
             
             ∝ 
             
               - 
               
                 
                   δ 
                    
                   
                       
                   
                    
                   m 
                 
                 m 
               
             
           
         
       
     
         [0019]    Where ω 0  is the resonant frequency of the device in the absence of analyte, δω 0  is the change in resonant frequency observed when an analyte is present within the device, m is the mass of the device and δm is the change in mass of the device when analyte is present. 
         [0020]    A further embodiment of the present invention is directed to a method for measuring changes in a solution. The method comprises the steps of providing a device having a primary conduit having a first fixed end, second fixed end, at least one first flex section, at least one second flex section and at least one analysis section. The first fixed end and the second fixed end are each for attachment to a base. The first flex section has a first flex section length and, similarly, the second flex section has a second flex section length. The first flex section and second flex section define a motion point distal to the first end and the second end in which the primary conduit has the greatest degree of motion. The motion point is for vibrating at a resonant frequency determined by the mass of the primary conduit and solutions carried with the primary conduit. The primary conduit has a first channel defining a fluid path for receiving solutions. The first channel has an inlet, an outlet. The first inlet is at the first fixed end and the first outlet at the second fixed end. The first analysis section has at least one curve comprising the first channel about the motion point and having an analysis length. The analysis length exceeds at least one half of one of the first conduit length and said second conduit length. The first conduit is for cooperating with means for inducing vibration and means for determining a resonant frequency to calculate a mass related parameter of the solution carried therein. The method further comprises the step of inducing vibration of the primary conduit and determining a resonant frequency of said first conduit as a function of the solutions flowing there through. 
         [0021]    Embodiments of the present method feature devices in which the analysis section has a larger volume than the channel positioned towards the proximal end. The volume of the analytical section, preferably, is larger by at least twenty percent the volume of the first channel that is not in the analytical section. A preferred method features a first channel having an analytical section that is in a serpentine or coil pattern. The coil or serpentine pattern places the analyte in solution about the longest arc of the arm, preferably, towards the last twenty five percent of the length of first arm, substantially corresponding to said longest arc at said distal end. 
         [0022]    Embodiments of the present method are well suited for analysis in conjunction with high performance liquid chromatography. Preferably, the first analysis section has a first analysis section volume and said first analysis section volume serves to focus the peak in the first analysis section. 
         [0023]    A further embodiment of the present method features a device having a primary conduit and a secondary conduit. The secondary conduit is in fluid communication with the primary conduit. The secondary conduit has a secondary first fixed end, a secondary second fixed end, at least one secondary first flex section and at least one secondary second flex section. The secondary first fixed end and the secondary second fixed end are each for attachment to a base. The secondary flex section has a secondary flex section length and the secondary second flex section has a secondary second flex section length. The secondary first flex section and secondary second flex section define a secondary motion point distal to the secondary first end and the secondary second end in which the secondary conduit has the greatest degree of motion. The motion point is for vibrating at a resonant frequency determined by the mass of said secondary conduit and solutions carried with the secondary conduit. The secondary conduit has a secondary channel defining a fluid path for receiving the solutions. The secondary channel has an secondary inlet, an secondary outlet, and at least one secondary analysis section. The first inlet is at the first fixed end and the first outlet is at the second fixed end. The secondary analysis section spans therebetween and defines a secondary channel volume. The second channel volume is smaller than the volume of the primary analysis section to allow measurement of mass parameters of a solution in the presence and absence of a peak in said first channel and said second channel. And, the method comprises the step of identifying at least one peak in said secondary conduit to allow determinations as to the mass of an analyte. 
         [0024]    Preferably, the secondary conduit and primary conduit are used with energy means and determining means. And, preferably, the method comprises the step of comparing the resonant frequency of the secondary conduit to the resonant frequency of the primary to determine the mass of one or more analytes flowing there through. 
         [0025]    Preferably, such determining means determines a mass change related to the presence of an analyte in accordance with the equation: 
         [0000]    
       
         
           
             
               
                 δω 
                 0 
               
               
                 ω 
                 0 
               
             
             ∝ 
             
               - 
               
                 
                   δ 
                    
                   
                       
                   
                    
                   m 
                 
                 m 
               
             
           
         
       
     
         [0026]    Where ω 0  is the resonant frequency of the device in the absence of analyte, δω 0  is the change in resonant frequency observed when an analyte is present within the device, m is the mass of the device and δm is the change in mass of the device when analyte is present. 
         [0027]    These and other features and advantages of the present invention will be apparent to those skilled in the art upon viewing the drawing and reading the detailed descriptions that follow. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0028]      FIG. 1  depicts a device embodying features of the present invention; 
           [0029]      FIG. 2  depicts a device embodying features of the present invention; 
           [0030]      FIG. 3  depicts a device embodying features of the present invention; 
           [0031]      FIG. 4  depicts a device, in partial cross section, embodying features of the present invention; 
           [0032]      FIG. 5  depicts a device, in partial cross section, embodying features of the present invention; and, 
           [0033]      FIG. 6  depicts a device embodying features of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0034]    Embodiments of the present invention will be described in detail with respect to preferred embodiments that feature devices and methods that provide an analytical value relating to mass of a compound. These devices and methods are well suited for use in conjunction with other analytical techniques such as chromatography but also for process controls in industrial processes. 
         [0035]    Turning first to  FIG. 1 , a device, for performing an analysis of a solution, embodying features of the present invention, generally designated by the numeral  11 , is depicted. The device  11  has a primary conduit  15  having a first fixed end  17 , second fixed end  19 , at least one first flex section  21 , at least one second flex section  23 , and at least one analysis section  25 . The first fixed end  17  and the second fixed end  19  are each for attachment to a base  27 . 
         [0036]    The base  27  is a solid mass intended to resist motion and vibration such that the first flex section  21  and the second flex section  23  are capable of movement and the first fixed end  17  and second fixed end  19  are substantially stationary. Thus, base  27  is selected to be relatively more massive and rigid than primary conduit  15 . Preferred materials for the base  27  include silica, metal and/or ceramic materials. Primary conduit  15  is preferably made of a material such as silica, metal, or ceramic. 
         [0037]    The first flex section  21  has a first flex section length and, similarly, the second flex section  23  has a second flex section length. As depicted, the first flex section  21  and second flex section  23  are substantially equal in length but do not need to be as long as the primary conduit has freedom to move. This movement is preferrably a vibrating motion, in which the primary conduit  15  moves radially about its axis or twists or rotates about an axis defined by the primary conduit  15 . The first flex section  21  and the second flex section  23  define a motion point  29 , apart from and distal to the first end  17  and said second end  19 . The motion point  29  is the place in which the primary conduit  15  has the greatest degree of motion. The motion point  29  is for vibrating at a resonant frequency determined by the mass of the primary conduit  15  and solutions carried with the primary conduit  15 . 
         [0038]    The first analysis section  25  has at least one curve  31  about the motion point and has an analysis length. The curve  31  can carry forward along a section of the primary conduit  15  to form a coil, as illustrated, or comprise many curves folding the primary conduit  15  in to a serpentine pattern to be described more fully with respect to other embodiments. The analysis length exceeds at least one half, one of the first flex section  21  length and the second flex section  23  length. The analysis section  25  focuses the mass of solutions carried in the primary conduit to the motion point providing increased sensitivity to changes in the solution mass. Longer analysis lengths, for example where the analysis length is at least as long as one of said first flex section  21  length and second flex section  23  length, allow for a sample of larger size. In applications where the device  11  is used with chromatographic systems [not shown], the analysis section  25  may have a length to define a volume that corresponds to a fraction of the volume of an analyte peak. An increase in the length of the analyte section  25  equaling or exceeding the volume of an analytical peak of a chromatography system, by five to twenty percent, is useful to ensure capture of the entire sample. 
         [0039]    The primary conduit  15  has a first channel  33  defining a fluid path for receiving said solutions. The first channel  33  has a first inlet  35  and a first outlet  37 . The first inlet  35  is at the first fixed end  17  and the first outlet  37  is at the second fixed end. The first conduit  15  is for cooperating with energy means [not shown] for inducing vibration and determining means [not shown] for determining a resonant frequency to calculate a mass related parameter of the solution carried therein. As used herein, energy means comprise mechanical, acoustic, optical, electrical, magnetic elements which impart kinetic energy to the primary conduit. The primary conduit  15  may comprise elements such as wires, magnetic, mechanical, or optical elements to facilitate the transfer of energy to the primary conduit  15  from the base  25 . 
         [0040]    As used herein, the determining means refers to a sensors [not shown] and readers [not shown] for determining the resonant frequency of the primary conduit  15  as solutions and samples flow through the first channel  33 . These sensors and readers are normally in signal communication with computational processing units (CPUs) [not shown] known in the art. CPUs are commonly integrated with instruments and computers, including by way of example personal, mainframe, servers and the like. As used herein, the term “signal communication” refers to being able to transmit or send or receive information in the form of electro magnetic or photo-optical transmissions or wired for direct transmission. 
         [0041]    Embodiments of the present invention can be built on a microfluidic scale and incorporated in microfluidic instruments and chromatographic systems. 
         [0042]    Turning now to  FIG. 2 , a further embodiment of the present invention, generally designated by the numeral  111 , is depicted. Device  111  has a primary conduit  115  having or in the form of a first arm, generally designated by the numeral  151 . The first arm  151  has a first length, first distal end  153 , and a first proximal end  155 . The first length is the distance between the first proximal end  155  and the first distal end  153  denoted by bracket B. The first proximal end  155  is attached to or constructed and arranged to attach to a base [not shown]. The first distal end  153  is free for vibrating at a resonant frequency determined by the mass of the primary conduit and solutions carried therein. The distal end  153  corresponds to the motion point  129 . 
         [0043]    The primary conduit  115  has a first fixed end  117 , second fixed end  119 , at least one first flex section  121 , at least one second flex section  123 , and at least one analysis section  125 . The analytical section  125  of the primary conduit  115  begins and ends at about the first curve  131   a  and last curve  131   b  in a series of curves and bends [not all are numbered for the purpose of clarity] to concentrate or gather the primary conduit  115  at the distal end  153  of the arm  151 . As depicted in  FIG. 2 , the primary conduit  115  is in the form of a serpentine pattern, however a coil or a combination of a coil and serpentine pattern or a random pattern which localizes the primary conduit  115  at the distal end  153  may be used. Concentrating the primary conduit  115  at the distal end  153  increases the sensitivity of the arm  151  to changes in mass caused by different concentrations of solute in the solutions. Preferably, the coil or serpentine pattern of the analytical section  125  is placed within the last twenty five percent of the length of the arm  151 . Additionally the internal diameter of conduit  115  within flex sections  121  and  123  may be substantially less than its internal diameter within the analytical section  125 . In another embodiment, the analytical section  125  of primary conduit  115  may comprises a portion where the outer diameter of conduit  115  is substantially larger that its outside diameter in the flex sections  121  and  123 . the transitions between these sections of differing inner and/or outer diameter may be discrete or continuous. 
         [0044]    One or more cross-members  171  are attached between flex sections  121  and  123  of which only one is shown. Cross member  171  serves to reduce any twisting modes of vibration of the device in which the flex sections  121  and  123  would move in opposite directions. 
         [0045]      FIG. 3  depicts a device  211 , similar to device  111  of  FIG. 2  such that all similar elements will be referred to with common numerical designations.  FIG. 3  depicts a device  211  in which the analytical section  125  is further aligned with the motion point  129  by concentrating the primary conduit  115  in plane substantially tangential to the arc of movement, denoted by arrows A-A. This alignment places a large volume of fluid potentially containing an analyte in the analytical section  125  where the device  211  is most sensitive to changes in mass. Embodiments featuring a arm place the coil or serpentine pattern close or at the most distal end. 
         [0046]    Embodiments of the present invention are well suited for fabrication as microfluidic devices.  FIG. 4  depicts a microfluidic device, generally designated by the numeral  311 , having features of common to those depicted in  FIG. 2  such that common elements will bear similar numeric designations. Device  311  has a primary conduit  115  having or in the form of a first arm, generally designated by the numeral  151 . The first arm  151  has a first length, first distal end  153 , and a first proximal end  155 . The first length is the distance between the first proximal end  155  and the first distal end  153 . The first proximal end  155  is attached to or constructed and arranged to attach to a base [not shown]. The first distal end  153  is free for vibrating at a resonant frequency determined by the mass of the primary conduit and solutions carried therein. The distal end  153  corresponds to the motion point  129 . 
         [0047]    Device  311  is planar made as a chip, tile or solid flat form of metal, ceramic and or plastic. The device  311  is made by molding, bonding layers, or the like. By way of example, without limitation, the device  311  is made by creating one of more top and bottom layers and one or more middle layers. The middle layers have fluidic patterns and are subsequently bonded, welded or glued to the top and bottom layers. 
         [0048]    A metallized strip  173  is secured to the section of device  311  toward distal end  153  to cooperate with energy means and determining means to be discussed more fully below. 
         [0049]      FIG. 5  depicts a microfluidic device, generally designated by the numeral  411 , having features of common to those depicted in  FIG. 3  such that common elements will bear similar numeric designations. Device  411  has a primary conduit  115  having or in the form of a first arm, generally designated by the numeral  151 . The first arm  151  has a first length, first distal end  153 , and a first proximal end  155 . The first length is the distance between the first proximal end  155  and the first distal end  153  denoted by bracket B. The first proximal end  155  is attached to or constructed and arranged to attach to a base [not shown]. The first distal end  153  is free for vibrating at a resonant frequency determined by the mass of the primary conduit and solutions carried therein. The distal end  153  corresponds to the motion point  129 . 
         [0050]    Device  411  is bi-planar made as a chip, tile or solid flat form or a group of chips, tiles or flat forms. Again, the device is comprised of metal, ceramic and/or plastic. The device  311  has an analytical section  125  in a plane corresponding to the tangent of the arc of the motion point  129 . The arc is denoted by arrows A-A. The device  411  can be made as a unitary structure or the analytical section  125  may be made separately from the first flex section  121  and second flex section  123  in the manner previously described. And, after the two sections are formed, they are combined and bonded, welded or glued as depicted in  FIG. 5 . 
         [0051]    Turning now to  FIG. 6 , a device generally designated by the numeral  511 , embodying features of the present invention is depicted. The device  511  has a primary conduit  515  which may comprise any of the forms describe thus far. The device  511  further comprises energy means  61  for inducing vibration in the first arm. As used herein, energy means  61  comprise mechanical, electrical, optical, acoustic, and magnetic mechanisms for imparting kinetic energy to the primary conduit  515  setting the primary conduit in motion. Depending on the form of energy means, the primary conduit  515  will be affixed to suitable cooperating elements to receive the energy. By way of example, without limitation, electro-magnetic energy means may require a metallized strip  173  as shown in  FIGS. 4 and 5 , magnetic strip or wires whereas optical or thermal energy means may have light or heat receiving surfaces. 
         [0052]    The primary conduit  515 , in response to the periodic application of such energy, will exhibit a resonant frequency in which the energy to induce and maintain such motion is most efficient, the resonant frequency. 
         [0053]    Device  511  further comprises determining means  63  for determining a resonant frequency of the primary conduit  515 . The determining means  63  for determining the resonant frequency is preferably in signal communication with the energy means  61  for inducing vibration in the primary conduit  515 . For example, without limitation, the determining means  63  monitors and/or controls the phase difference between the energy means and the sensing devices detect the motion. Thus, determining means  63  comprises sensors for detecting the movement of the primary  63  conduit  515  and/or energy consumption of the energy means  61 . The determining means further comprises computational processing units (CPUs) for processing the signals and data. The CPUs may be integral to existing equipment or associated with a free standing computer-type device such as a personal computer, mainframe computer or server. 
         [0054]    Preferably, determining means  63  compares the resonant frequency or the energy consumption of the primary conduit  515  in the presence or potential presence of an analyte and compares the value to a standard. The comparison relates to the density and/or mass of one or more solutions flowing through the first channel. 
         [0055]    One preferred device  511  features a primary conduit  515  as described and further comprises a secondary conduit  75 . The secondary conduit  75  is in fluid communication with the primary conduit  515 . As used herein, the term “fluid communication” means commonly plumbed. 
         [0056]    The secondary conduit  75  has a secondary first fixed end  79 , a secondary second fixed end  81 , at least one secondary first flex section  83  and at least one secondary second flex section  85 . The secondary first fixed end  81  and the secondary second fixed end  83  are each for attachment to a base [not shown]. The secondary first flex section  83  has a secondary flex section length and, similarly, the secondary second flex section  85  has a secondary second flex section length. The secondary first flex section  83  and secondary second flex section  85  define a secondary motion point  629  distal to the secondary first end  83  and the secondary second end  85  in which the secondary conduit has the greatest degree of motion. The motion point  629  is for vibrating at a resonant frequency determined by the mass of the secondary conduit and solutions carried with the secondary conduit. 
         [0057]    The secondary conduit has a secondary channel [not shown] in the nature of the first channel  33  described in previous embodiments of the primary conduit. The passage defines a fluid path for receiving the solutions. And, the secondary channel has a secondary inlet and a secondary outlet. The first inlet is at the secondary first fixed end and the first outlet at the secondary second fixed end. The secondary analysis section spans therebetween and defines a secondary channel volume. The volume of the second channel may be the same or different that the volume of the first channel 
         [0058]    Preferably, the second conduit  75  allows measurement of at least one mass parameter of a solution in which the analyte is the present in one of the first channel and second channel and absent in the other. Thus, the difference in mass of the analyte can be directly related to the differences in resonance of the primary conduit  515 . 
         [0059]    The device  511  further comprise energy means [not shown], in the nature previously described with respect to the primary conduit  515 , for inducing vibration in said second conduit  75 . And, the device further comprises determining means [not shown] for determining the resonant frequency of said second conduit  75  in the nature of that previously described with primary conduit  515 . 
         [0060]    An additional benefit to the use of one or more secondary volumes is that signals that may result from external extraneous influences are more easily rejected. 
         [0061]    As depicted, device  511  further comprises a chromatography system  91  for separating samples into concentrations of compounds identified on detectors as peaks. The chromatography system is in fluid communication first with the secondary conduit  75  and then the primary conduit  515 . The secondary conduit  75  receives the fluid from the chromatography system and identified the peak of compounds. The peak so identified allows the primary conduit  515  to relate the presence of the peak to a mass represented by the change in resonance. 
         [0062]    Preferably, such determining means determines a small mass change related to the presence of an analyte in accordance with the equation: 
         [0000]    
       
         
           
             
               
                 δω 
                 0 
               
               
                 ω 
                 0 
               
             
             ∝ 
             
               - 
               
                 
                   δ 
                    
                   
                       
                   
                    
                   m 
                 
                 m 
               
             
           
         
       
     
         [0063]    Where ω 0  is the resonant frequency of the device in the absence of analyte, δω 0  is the change in resonant frequency observed when an analyte is present within the device, m is the mass of the device and δm is the change in mass of the device when analyte is present. 
         [0064]    A further embodiment of the present invention, directed to a method for measuring changes in a solution, will be described with respect to the operation of the device depicted in  FIGS. 3 and 6 . In operation, a device  211 , having a primary conduit  115  having a first fixed end  117 , second fixed end  119 , at least one first flex section  121 , at least one second flex section  123  and at least one analytical section  125 . The first fixed end  117  and the second fixed end  119  are each for attachment to a base [not shown]. The first flex section  117  has a first flex section length and, similarly, the second flex section  119  has a second flex section length. The first flex section  117  and second flex section  119  define a motion point  129  distal to the first end  117  and the second end  119  in which the primary conduit  115  has the greatest degree of motion. The motion point  129  is for vibrating at a resonant frequency determined by the mass of the primary conduit  115  and solutions carried with the primary conduit  115 . The primary conduit  115  has a first channel  133  defining a fluid path for receiving solutions. The first channel has an inlet and an outlet. The first inlet is at the first fixed end  117  and the first outlet at the second fixed end  119 . The first analysis section  125  has at least one curve comprising the first channel  133  about the motion point  129  and having an analysis length. The analysis length exceeds at least one half of one of the first conduit length and said second conduit length. The first conduit  115  is for cooperating, referring now to  FIG. 6 , with energy means  61  for inducing vibration and determining means  63  for determining a resonant frequency to calculate a mass related parameter of the solution carried therein. The method further comprises the step of inducing vibration of the primary conduit  115  and determining a resonant frequency of the first conduit  115  as a function of the solutions flowing there through. 
         [0065]    In conjunction with high performance liquid chromatography, referring back to  FIG. 3 , the first analysis section  125  has a first analysis section volume and the first analysis section volume corresponds to a high performance liquid chromatography peak volume of the analyte to focus the peak in such first analysis section  125 . 
         [0066]    Returning now to  FIG. 6 , the device  511  having a primary conduit  515  and a secondary conduit  75 , utilizes the secondary conduit  75  to identify the volume of the flow corresponding to the peak and potentially as a reference standard. That is, where the primary conduit  515  and secondary conduit  75  are similar in configuration, one conduit can be used as a reference standard to the other as sample pass through. 
         [0067]    The mass of an analyte is calculated in accordance with the equation: 
         [0000]    
       
         
           
             
               
                 δω 
                 0 
               
               
                 ω 
                 0 
               
             
             ∝ 
             
               - 
               
                 
                   δ 
                    
                   
                       
                   
                    
                   m 
                 
                 m 
               
             
           
         
       
     
         [0068]    Where ω 0  is the resonant frequency of the device in the absence of analyte, δω 0  is the change in resonant frequency observed when an analyte is present within the device, m is the mass of the device and δm is the change in mass of the device when analyte is present. 
         [0069]    Determining means  63  is preferably programmed to make such calculation. 
         [0070]    These and other features and advantages of the present invention will be apparent to those skilled in the art upon viewing the drawing and reading the detailed descriptions that follow.