Abstract:
Disclosed is a biopolymer (DNA) detector capable of performing overall analysis including an unreacted sample without needing any complex work such as washing or the like. A DNA probe  66  is fixed to an electrode plate  22,  and the electrode plate  22  is displaced by applying a DC voltage between electrode plates  22  and  23.  Thus, sample DNA  63  to be detected can be separated. It becomes possible to obtain a clearer result by performing analysis based on a ratio of an entire reaction system.

Description:
PRIORITY INFORMATION  
         [0001]    This application claims priority to Japanese Application Serial No. 2001-25889, filed Feb. 1, 2001.  
         BACKGROUND OF THE INVENTION  
         [0002]    The present invention relates to a biopolymer detector capable of detecting presence/absence of biopolymers such as DNA, RNA, protein or the like in a sample, and measuring a present amount or a concentration thereof.  
           [0003]    A typical method of a conventional DNA detection technology has been to modify DNA with a radioactive material, fluorescent dye or the like by using a radioactive isotope (RI), fluorescence technology or the like, excite the DNA by an external stimulus, and then observe its response based on light emission. A charge detection method has also been invented, which makes electrochemical determination by using intercalating agents specifically coupled to DNA double strands, and based on an oxidation reduction potential thereof. Moreover, as a method which needs no modification or the like, a method making use of a surface plasmon resonance phenomenon has been available. Regarding a technology for fixing DNA to an electrode, a method using a thiol-modified DNA probe or the like has been available, which utilizes an action in which a monomolecular film of a free thiol group at the tail end of the DNA forms itself on a full surface.  
         SUMMARY OF THE INVENTION  
         [0004]    Among the methods made available in the conventional DNA detection technology, it was necessary to modify the DNA in case of using the RI or fluorescence technology.  
           [0005]    The present invention provides a biopolymer (DNA) detector capable of performing direct detection by using the property of DNA without needing any modification of the DNA.  
           [0006]    A biopolymer detector according to an aspect of the invention comprises: voltage supplying means for applying a voltage between two electrodes of a casing for housing biopolymers between the electrodes; and measuring means for measuring an electrical characteristic between the electrodes, alternatively a change in the electrical characteristic.  
           [0007]    A biopolymer detector according to another aspect of the invention comprises: voltage supplying means for applying a voltage between two electrodes of a casing for housing biopolymers between the electrodes; electrode driving means for changing a distance between the electrodes; and measuring means for measuring an electrical characteristic between the electrodes, alternatively a change in the electrical characteristic.  
           [0008]    The voltage supplying means can selectively supply AC or DC voltages, and can draw biopolymers to one or both of the electrodes.  
           [0009]    The measuring means can further includes arithmetic processing means for calculating one selected from presence/absence of biopolymers between the electrodes, a present amount, a base length, a concentration, a rate of hybridization, and an amount of hybridization based on a measuring result of the electrical characteristic, alternatively a change in the electrical characteristic. Thus, various characteristic amounts of biopolymers can be measured.  
           [0010]    Heating means can be further provided for applying heat to the electrodes to dissociate hybridized biopolymers between the electrodes into a single strand. Thus, the presence of complementary strand biopolymers and non-complementary strand biopolymers can be respectively detected.  
           [0011]    According to the detector of the invention, it is only necessary to inject sample DNA between the opposing electrodes. According to this technology, since the amount of present DNA can be physically measured, a concentration or the like can also be measured. Moreover, in the detector, by applying the external force of an electric field to the opposing electrodes, single-strand probe DNA fixed to the electrode surface, and sample DNA that has not been hybridized are drawn to the electrode, to which the probe DNA is not fixed. Accordingly, gene detection can be carried out without needing any washing.  
           [0012]    Furthermore, both reacted and unreacted samples are measured by employing the method of the invention. Thus, a clearer result can be obtained.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0013]    [0013]FIG. 1 is a schematic diagram showing a configuration of a biopolymer detector  1  according to an embodiment of the present invention.  
         [0014]    FIGS.  2 ( a ) to  2 ( c ) are views, each showing a behavior of DNA  61  when a DC voltage is applied between electrode plates  22  and  23 .  
         [0015]    FIGS.  3 ( a ) and  3 ( b ) are views, each showing a behavior of DNA  62  when an AC voltage is applied between the electrode plates  22  and  23 .  
         [0016]    FIGS.  4 ( a ) to  4 ( f ) are views, each showing a first detection example by the biopolymer detector  1  of the embodiment, to which DNA position control is applied.  
         [0017]    [0017]FIG. 5 is a view showing an example of a detection result obtained from an electrical characteristic between the electrode plates  22  and  23 , for example a result of measuring a current i flowing between the electrode plates  22  and  23 , in the first detection example.  
         [0018]    FIGS.  6 ( a ) to  6 ( d ) are views, each showing a second detection example by the biopolymer detector  1  of the embodiment, to which the DNA position control is applied.  
         [0019]    [0019]FIG. 7 is a view showing an example of a detection result obtained from a result of measuring an electrical characteristic signal between the electrode plates  22  and  23  in the second detection example. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0020]    Hereinafter, detailed description will be made for the preferred embodiment of the present invention with reference to the accompanying drawings.  
         [0021]    [0021]FIG. 1 is a schematic diagram showing a configuration of a biopolymer detector  1  according to the embodiment of the invention.  
         [0022]    According to the embodiment, the biopolymer detector  1  roughly comprises a power supply unit  10 , an electrode plate unit  20 , a measuring unit  40 , and a computer  50  as control means for controlling each of these sections.  
         [0023]    In the embodiment, the power supply unit  10  includes a DC power supply section  11  for generating a DC voltage, and an AC power supply section  12  for generating an AC voltage.  
         [0024]    The power supply unit  10  selectively supplies/cuts off a DC voltage or an AC voltage to the electrode plate unit  20  based on a control signal from voltage application control means  51  provided in the computer  50 .  
         [0025]    The electrode plate unit  20  includes a pair of electrode plates  22  and  23  disposed opposite to each other in a cylinder-shaped casing  21 . A space in the casing  21 , which is defined between the electrode plates  22  and  23 , forms a solution reservoir  24  for storing a solution prepared by using later-described biopolymers as solutes.  
         [0026]    In the wall surface of the casing  21  around the solution reservoir  24 , an opening  25  is formed for storing the solution in the solution reservoir  24 , discharging the solution stored in the solution reservoir  24  to the outside thereof, or the like.  
         [0027]    The electrode plate  22  of one side is connected to the output of the above-described power supply unit  10 , while the electrode plate  23  of the other side is grounded in the embodiment. Thus, an electric circuitry including the electrode plate unit  20  as a circuit component is composed with respect to the power supply unit  10 .  
         [0028]    In FIG. 1, wires respectively connecting the power supply unit  10  with the electrode plate  22 , and the electrode plate  23  with the ground are shown to be connected to the electrode plates  22  and  23  from the front sides (i.e., opposite sides) thereof through the opening  25  for convenience. In actual configuration, however, the wires are connected to the backsides or side faces of the electrode plates  22  and  23  not through the opening  25 , but through another not-shown opening of the casing  21 , and no wires are disposed in the solution reservoir  24 .  
         [0029]    In the case of the electrode plate unit  20  of the embodiment, the electrode plate  22  of one side has its backside inseparably attached to a movable plate  26 , which is provided in the casing  21  so as to be axially displaced. Thus, the electrode plate  22  is displaced in the united manner with the movable plate  26 . On the other hand, the electrode plate  23  of the other side is attached to the bottom of the casing  21  of the backside thereof so as to be fixed through an attaching member  27 . Thus, the electrode plate  23  is prevented from being axially displaced in the casing  21 .  
         [0030]    A tip side of a rod  28  similarly provided in the casing  21  which is capable of axial displacement is connected to the backside of the movable plate  26 , i.e., the surface of a side opposite the electrode plate  22 . The base end side of the rod  28  is connected to the rotary shaft  31   a  of a motor  31  (e.g., stepping motor or the like) through a rotation/linear motion conversion mechanism  29  for converting a rotational motion into a linear motion, and a deceleration mechanism  30  for decelerating the rotational motion.  
         [0031]    Here, for example, the deceleration mechanism  30  is composed of a gear connected to the rotary shaft  31   a  of the motor  31 , and the rotational speed of the rotary shaft  31   a  of the motor  31  is reduced at a predetermined rate. A rotation/linear motion conversion mechanism  29  converts the rotational motion of the output shaft, not shown, of the deceleration mechanism  30  into a linear motion in the axial direction of the casing  21 . The rotation/linear motion conversion mechanism  29  is composed of, for example, a cylindrical member rotated in a united manner with the not-shown output shaft of the deceleration mechanism  30 , and having a screw part formed in its inner peripheral surface, and the base end side portion of the rod  28  having a screw provided in the base end side outer peripheral surface to be engaged with the inner peripheral surface screw part of the cylindrical member. By engaging the base end side of the rod  28  with the cylindrical member, and rotating the cylindrical member while the rotation of the rod  28  is regulated, the rod  28  is moved back and forth according to the rotational direction thereof. In this case, the rotation of the motor  31  is transmitted through the deceleration mechanism  30  to the cylindrical member. Thus, even without any control of the rotational amount of the motor  31  by a small rotational amount unit, the rod  28  can be moved back and forth linearly by a small distance unit. The motor  31  is controlled for driving or rotation based on a control signal outputted from inter-electrode distance control means  52  provided in the computer  50 .  
         [0032]    In addition, in the outer peripheral surface of the casing  21  around the solution reservoir  24 , a heater  32  is provided as heating means. The heater  32  operates to heat a solution stored in the solution reservoir  24 .  
         [0033]    The measuring unit  40  is connected into the electric circuitry including the electrode plate unit  20  as the circuit component, and adapted to measure an electrical characteristic, or a change in the electrical characteristic of the electric circuitry including the electrode plate unit  20 , in other words an electrical characteristic or a change in the electrical characteristic between the electrode plates  22  and  23 . Here, as such an electrical characteristic, one can be selected from a voltage, impedance of resistance or the like, a frequency, and the like.  
         [0034]    According to the embodiment, a characteristic value measured by the measuring unit  40  is supplied to arithmetic processing means  53  provided in the computer  50 . The arithmetic processing means  53  analyzes the measuring result of the measuring unit  40 , and the result of the analysis is displayed on a display  55 .  
         [0035]    Next, description will be made for a method for detecting biopolymers, which uses the foregoing biopolymer detector  1  of the embodiment composed as described above.  
         [0036]    It is known that DNA as a biopolymer emits a current substantially equal to the level of an existing electroconductive polymer.  
         [0037]    Thus, description will be made for a behavior of DNA when a solution containing DNA as a solute is stored in the solution reservoir  24  formed between the electrode plates  22  and  23  of the biopolymer detector  1 , and a voltage is applied between the electrode plates  22  and  23 .  
         [0038]    Each of FIGS.  2 ( a ) to  2 ( c ) shows a behavior of DNA  61  when a DC voltage is applied between the electrode plates  22  and  23 .  
         [0039]    When a DC voltage is applied between the electrode plates  22  and  23 , the DNA  61  is pulled in an electric field direction shown by an arrow in the drawing, and drawn to one electrode plate (the electrode plate  23  in this case) side.  
         [0040]    Thus, as shown in FIG. 2( a ), probe DNA  65  is fixed to the electrode plate  22 , and a solution containing sample DNA  61  as a solute is stored in the solution reservoir  24  formed between the electrode plates  22  and  23 . Then, as shown in FIG. 2( b ), a DC voltage is applied after hybridization reaction. Subsequently, as shown in FIG. 2( c ), hybridized complementary strand sample DNA  61   a  is extended because it is coupled to the probe DNA  65  at the electrode plate  22  side. However, non-complementary strand sample DNA  61   b  that has not been hybridized is drawn to the electrode plate  23  side, and contracted.  
         [0041]    Therefore, in this state, by using the measuring unit  40  to measure an electrical characteristic such as electrical energy or the like between the electrode plates  22  and  23 , it is possible to detect presence/absence of the hybridized complementary strand sample DNA  61   a , and measure the present amount.  
         [0042]    Each of FIGS.  3 ( a ) and  3 ( b ) shows the behavior of DNA  62  when an AC voltage is applied between the electrode plates  22  and  23 .  
         [0043]    As shown in FIG. 3( a ), a solution containing DNA  62  as a solute is stored in the solution reservoir  24  formed between the electrode plates  22  and  23 .  
         [0044]    When an AC voltage is applied between the electrode plates  22  and  23 , by a frequency and a voltage within certain ranges (10 6  V/m, and 1 MHz in the present device), as shown in FIG. 3( b ), the DNA  62  is drawn from a position immediately before the voltage application to either side of the electrode plates  22  and  23  located nearer in its extended state. In FIGS.  3 ( a ) and  3 ( b ), a reference numeral  62   a  denotes the DNA  62  positioned not in the electrode plate  23  but in the electrode plate  22  side;  62   b  DNA  62  positioned in not in the electrode plate  22  but in the electrode plate  23  side.  
         [0045]    Therefore, in the state where the solution containing the DNA  61  and  62  as solutes in the solution reservoir  24  formed in the electrode plates  22  and  23 , it is possible to control the positions of the DNA  61  and  62  by properly using DC and AC voltages to be applied between the electrode plates  22  and  23 .  
         [0046]    In addition, accordingly, regarding an electrical characteristic, or a change in the electrical characteristic of the electric circuitry including the electrode plate unit  20 , in other words, an electrical characteristic or a change in the electrical characteristic between the electrode plates  22  and  23 , it is possible to change the electrical characteristic between the electrode plates  22  and  23 , between a case containing DNA  61   a  and  62  in the solution stored between the electrode plates  22  and  23 , and a case containing no such DNA.  
         [0047]    Now it is assumed, for example, that the electrical characteristic between the electrode plates  22  and  23  can be measured beforehand in the case containing DNA  61   a  and  62  in the solution stored between the electrode plates  22  and  23 , or the case containing no such DNA, and established as a condition for comparison. In this case, by relatively comparing the result of measuring the electrical characteristic in the case containing no DNA  61   a  or  62  (or the case of containing such DNA) with the result of measurement to satisfy the condition for comparison, it is possible to detect the case containing no DNA  61   a  or  62  (or the case containing such DNA).  
         [0048]    Next, description will be made for another method for detecting DNA, which uses the biopolymer detector  1  of the embodiment, and to which the foregoing DNA position control is applied.  
         [0049]    Each of FIGS.  4 ( a ) to  4 ( f ) shows a first detection example by the biopolymer detector  1  of the embodiment, to which the DNA position control is applied.  
         [0050]    This detection example is one, where DNA  63  in the solution stored between the electrode plates  22  and  23  is extended by applying a DC voltage between the electrode plates  22  and  23 , and a distance between the electrode plates  22  and  23  is controlled by driving and controlling the motor  31 , thus detecting various DNA  63   a ,  63   b  and  63   c  having different base lengths by differentiating them from one another.  
         [0051]    In the detection example, as shown in FIG. 4( a ), a single-strand DNA probe  66  having a specific base sequence is fixed to one of the opposing electrode plates  22  and  23 , i.e., the electrode plate  22 .  
         [0052]    On the other hand, in the solution reservoir  24  between the electrode plates  22  and  23   a , a solution containing sample DNA  63  denatured into a single strand as a solute is stored. As shown in FIG. 4( b ), the sample DNA  63  is hybridized with the above-described single-strand DNA probe  66 .  
         [0053]    Then, an electric field is generated between the electrode plates  22  and  23  by driving and controlling the power supply unit  10  and, as shown in FIG. 4( c ), the single-strand DNA probe  66  and the sample DNA  63  denatured into a single-strand are extended.  
         [0054]    The hybridization of the sample DNA  63  with the single-strand DNA probe  66  may be performed in the following manner. That is, as shown in FIG. 4( d ), a DC voltage is applied between the electrode plates  22  and  23 , and the sample DNA  63  is mixed in a solvent of the extended single-strand DNA probe  66 . Then, hybridization reaction is caused between the single-strand DNA probe  66  and the sample DNA  63   a ,  63   b  and  63   c  in their extended states. Thus, a state like shown in FIG. 4( c ) is realized.  
         [0055]    In the above state, it is assumed that a distance d between the electrode plates  22  and  23  is maintained at an initially set distance d0 properly set beforehand, based on the base lengths of the single-strand DNA probe  66  and the sample DNA  63  denatured into a single strand.  
         [0056]    In a state shown in FIG. 4( d ), sample DNA  63   d  that has not been hybridized with the single-strand DNA probe  66  fixed to the electrode plate  22  is drawn to the electrode plate  23  to be deposited. Thus, this sample DNA  63   d  has no direct influence on detection. In other words, no washing is necessary in a detection process.  
         [0057]    Then, in the present detection example, from the above-described state, the stepping motor  31  is driven and controlled to bring the electrode plate  22  closer to the electrode plate  23  side for small distances. Accordingly, the distance d between the electrode plates  22  and  23  is reduced for small distances to the initially set distance d0.  
         [0058]    Then, following the reduction of the distance d between the electrode plates  22  and  23  like shown in FIG. 4( e ) or  4 ( f ), electrical characteristics such as a voltage, impedance of resistance or the like, a frequency, and the like for each distance are sequentially measured by the measuring unit  40 . By comparison of time-wise changes in the measured values of such electrical characteristics, or momentary measured values, genes, i.e., biopolymers, are detected.  
         [0059]    [0059]FIG. 5 shows an example of a detection result obtained from an electrical characteristic between the electrode plates  22  and  23 , for example the result of measuring the current i flowing between the electrode plates  22  and  23 .  
         [0060]    This example of the detection result is a simple representation of a relationship between the distance d between the electrode plates  22  and  23  and the current i flowing between the electrode plates  22  and  23  measured by the measuring unit  40 , the distance d being taken as the abscissa, and the current i as the ordinate.  
         [0061]    In FIG. 5, when the distance d between the electrode plates  22  and  23  is d0, neither of the tips of the sample DNA  63  denatured into a single strand and the single-strand DNA probe  66  drawn to the electrode plate  22  and set in the extended states as shown in FIG. 4( c ) are not in contact with the electrode plate  23 .  
         [0062]    Accordingly, the current i hardly flows through the electrode plate unit  20 , and the size of the current i measured by the measuring unit  40  is i0 (nearly 0).  
         [0063]    Then, the distance d between the electrode plates  22  and  23  becomes d1 (d1&lt;d0), and only the tip of the sample DNA  63   a  having the longest base length among the sample DNA  63  shown in FIG. 4( c ) is brought into contact with the electrode plate  23 . Different from the sample DNA  63   a , when the sample DNA  63   b  and the sample DNA  63   c  having shorter base lengths are not in contact with the electrode plate  23 , the current i flows through the sample DNA  63   a  between the electrode plates  22  and  23 , and the size of a current measured by the measuring unit  40  is increased from i0 to i1.  
         [0064]    Then, when the distance d between the electrode plates  22  and  23  becomes d2 (d2&lt;d1), and the tip of the sample DNA  63   b  is brought into contact with the electrode plate  23  in addition to the sample DNA  63   a  as shown in FIG. 4( e ), the current i also flows through the sample DNA  63   b  between the electrode plates  22  and  23 , in addition to the sample DNA  63   a . Accordingly, the size of a current measured by the measuring unit  40  is increased from i1 to i2.  
         [0065]    Then, when the distance d between the electrode plates  22  and  23  becomes d3 (d3&lt;d2), and the tip of the sample DNA  63   c  having a shorter base length is brought into contact with the electrode plate  23  in addition to the sample DNA  63   a  and the sample DNA  63   b , the current i also flows through the sample DNA  63   c  between the electrode plates  22  and  23 , in addition to the sample DNA  63   a  and  63   b . Accordingly, the size of a current measured by the measuring unit  40  is increased from i2 to i3.  
         [0066]    Then, when the distance d between the electrode plates  22  and  23  becomes d4 (d4&lt;d3), and the tip of the DNA probe  66  having a further shorter base length is brought into contact with the electrode plate  23  in addition to the sample DNA  63   a ,  63   b  and  63   c  as shown in FIG. 4( f ), the current i also flows through the DNA probe  66  between the electrode plates  22  and  23 , in addition to the sample DNA  63   a ,  63   b  and  63   c . Accordingly, the size of a current measured by the measuring unit  40  is further increased from i3 to i4.  
         [0067]    In FIG. 5, the size portion of the current i indicated by A represents a signal portion by the sample DNA  63   a ,  63   b  and  63   c . The size portion of the current i indicated by B represents a signal portion by the DNA probe  66 .  
         [0068]    As a result, for example, depending on the size of the current i through the electrode plate unit  20  and the time-wise change, presence/absence or the amount of the sample DNA  63   a ,  63   b  and  63   c  having different base lengths or the like can be calculated. Also, depending on the distance d between the electrode plates  22  and  23  when a conspicuous change occurs in the size of the current i, the base length or the like of each sample DNA  63   a ,  63   b  and  63   c  can be calculated by the arithmetic processing means  53  provided in the computer  50 .  
         [0069]    Each of FIGS.  6 ( a ) to  6 ( d ) shows a second detection example by the biopolymer detector  1  of the embodiment, to which the foregoing DNA position control is applied.  
         [0070]    In this detection example, as shown in FIG. 6( a ), sample DNA  64  propagated by the polymerase chain reaction (PCR) is injected and stored in the solution reservoir  24  formed between the electrode plates  22  and  23 , and a high frequency voltage (AC voltage) of, e.g., 10 6  V/m and 1 MHz is applied by driving and controlling the power supply unit  10 .  
         [0071]    Accordingly, as shown in FIG. 6( b ), the sample DNA  64  is drawn from a position immediately before the voltage application to either side of the electrode plates  22  and  23  located nearer in an extended state.  
         [0072]    In the detection example, from this state, the stepping motor  31  is driven and controlled to bring the electrode plate  22  closer to the electrode plate  23  side for small distances, and the distance d between the electrode plates  22  and  23  is reduced to the initially set distance d0 for small distances.  
         [0073]    Then, following the reduction of the distance d between the electrode plates  22  and  23  as shown in FIG. 6( c ) or  6 ( d ), electrical characteristics such as a voltage, impedance of resistance or the like, a frequency, and the like for each distance are sequentially measured by the measuring unit  40 . By comparing time-wise changes in the measured values of such electrical characteristics, or momentary measured values, genes, i.e., biopolymers, are to be detected.  
         [0074]    [0074]FIG. 7 shows an example of a detection result obtained from the result of measuring an electrical characteristic signal between the electrode plates  22  and  23 .  
         [0075]    Also in this case, if only sample DNA  64   a  having a constant base length is present as sample DNA  64 , a conspicuous increase occurs in a measured value D by changing the distance d between the electrode plates  22  and  23 . Specifically, a conspicuous increase A appears in the measured value D of an electrical characteristic signal between the measured value D1 of the electrical characteristic signal when the sample DNA  64   a  provides no bridge between the electrode plates  22  and  23  as shown in FIG. 6( b ) and  6 ( c ), and the size D2 of the electrical characteristic signal when the sample DNA  64   a  provides a bridge between the electrode plates  22  and  23  as shown in FIG. 6( d ).  
         [0076]    For example, when there are one or two places of such conspicuous increase A portions, it indicates that only the DNA  64  having a constant base length is present, making it possible to confirm the success of PCR.  
         [0077]    When there are no such conspicuous increase A portions, it indicates that no DNA are present between the electrode plates  22  and  23 . In addition, when there are three or more such conspicuous increase A portions, it indicates that DNA  64   a ,  64   b , □having different base lengths present in a number equal to the number of such conspicuous increase A portions.  
         [0078]    Further, in the biopolymer detector  1  of the embodiment, by varying temperatures at the heater  32 , the amount of DNA hybridized/non-hybridized at each temperature is measured for also making it possible to measure a single-strand dissociation temperature of DNA.  
         [0079]    In the measurement and detection by the biopolymer detector  1  of the embodiment, the sample DNA  61  to  64  can be measured and detected in their unmodified states. To increase sensitivity, however, the sample DNA  61  to  64  may be modified by an organic or inorganic material such as fluorescent dye or the like, by applying an external stimulus or the like.  
         [0080]    The biopolymer detector  1  of the embodiment is composed in the foregoing manner. However, the structure of the power supply unit  10  as voltage supplying means, the structure as electrode driving means including the rotation/linear motion conversion mechanism  29 , the deceleration mechanism  30 , the motor  31 , and the like, and the detection structure of the measuring unit  40  as measuring means, are not limited to the foregoing structures. Various modifications can be employed, for example by using a linking mechanism as electrode driving means, or by using an electromagnet in place of the motor, and others.  
         [0081]    According to the biopolymer detector of the invention, presence/absence of biopolymers such as DNA, RNA, protein or the like, a present amount, or a concentration in a sample can be easily measured without modifying the biopolymers.