Abstract:
A system and method for thermal gradient gas chromatography wherein a front or injection end of a column is heated to a higher temperature than a back or detector end to thereby create a thermal gradient having a profile that is substantially monotonically non-increasing and has a positive second derivative, and then providing a heat source to raise the thermal gradient and cause it to remain stationary or to travel through the column while maintaining a desired profile.

Description:
BACKGROUND 
     Description of Related Art 
     Gas chromatography (GC) may be a widely used analytical technique for the analysis of gases, and volatile and semi-volatile organic compounds, due to its simplicity, high separation efficiency and relatively short analysis time. 
       FIG. 1  is a block diagram that is provided to show that some of the principle components of a GC system may be described as a tube, channel or column  10  (hereinafter referred to as a “column”), an injector  12  by which a sample may be injected into the column, a temperature regulation system  14  with which the temperature of the column may be established and controlled through the duration of a separation process, and a detector  16  that may detect analytes eluting from the column. It should be understood that there are many modifications that may be made to the system shown in  FIG. 1  without departing from the subject matter of the invention. 
     The process of controlling the temperature within the column  10  may be controlled by a computer to ensure that the temperature at any point in time is at a predetermined set value. The temperature regulation system  14  that may be used to heat the column  10  and to maintain the column at a specific temperature may be an oven. However, other temperature regulation systems include but should not be considered as limited to vapor jackets, oil baths, Dewar flasks, heat exchanger, air bath oven, resistive heating, infra-red heating, inductive heating and microwave heating. 
     There are different implementations of GC, including isothermal where the column temperature is held fixed for the entire separation, and programmed temperature where the entire column is gradually heated throughout the separation to increase the column temperature in a predetermined, programmed manner. What is important to understand about these prior art methods is that the temperature of the column is substantially uniform along its entire length. In other words, variations in temperature may only be unintentional or caused by limitations of the heating method being used. 
     BRIEF SUMMARY 
     The present invention is a system and method for thermal gradient gas chromatography wherein a front or injection end of a column is heated to a higher temperature than a back or detector end to thereby create a thermal gradient having a profile that is substantially monotonically non-increasing and has a substantially non-negative second derivative, and then providing a heat source to shift upward the thermal gradient, wherein the thermal gradient may include a finite portion where the thermal gradient may be strictly negative. 
     In a first aspect of the invention, a gas chromatograph is provided that includes an injector, a column and a detector, with the column having a front end for receiving a sample from the injector, and a back end for elution of the sample into the detector. 
     In a second aspect of the invention, a first heating device is used for applying primary heat to the column to create a thermal gradient along at least a portion of the column, and wherein at least some portion of the thermal gradient is negative. 
     In a third aspect of the invention, a second heating device is used for applying secondary heat to the column to thereby raise, translate or shift upwards the thermal gradient of the column. 
     In a fourth aspect of the invention, the thermal gradient is substantially monotonically non-increasing and the thermal gradient has a substantially non-negative second derivative. 
     These and other embodiments of the present invention will become apparent to those skilled in the art from a consideration of the following detailed description taken in combination with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
         FIG. 1  is a block diagram of the components that may be part of a gas chromatography system in the prior art. 
         FIG. 2  is an example of a thermal gradient curve of a first embodiment that has a smooth curve. 
         FIG. 3  is a graph of a thermal gradient curve of a first embodiment where the thermal gradient curve has segments that are linear or non-increasing. 
         FIG. 4  is a graph of a thermal gradient curve that is comprised of piece-wise or step-wise linear segments and that has at least one segment that is increasing. 
         FIG. 5  is a graph of a thermal gradient curve that is comprised of a combination of smooth segments and piece-wise or step-wise linear segments. 
         FIG. 6  is a graph of a thermal gradient curve that is shifted upwards while maintaining the original profile. 
         FIG. 7  is provided as a perspective view of a first column and substrate of a thermal gradient GC that can be used to create the desired thermal gradient. 
         FIG. 8  is provided as a perspective and profile view of a second column and substrate of a thermal gradient GC that can also be used to create the desired thermal gradient. 
         FIG. 9  is a graph of a thermal gradient curve having a first section with a linear negative slope and a second section that is isothermal. 
     
    
    
     DETAILED DESCRIPTION 
     Reference will now be made to the drawings in which the various embodiments of the present invention will be given numerical designations and in which the embodiments will be discussed so as to enable one skilled in the art to make and use the invention. It is to be understood that the following description illustrates embodiments of the present invention, and should not be viewed as narrowing the claims which follow. 
     The first embodiment of the present invention is the creation of a desired thermal gradient within a column. It is understood that there may be many different hardware configurations of a gas chromatograph that may be constructed in order to achieve the desired thermal gradient profile. Accordingly, the first embodiment should not be considered to be limited to any particular hardware configuration, but only to a gas chromatograph that can achieve the desired thermal gradient profile. 
       FIG. 2  is a graph of a first embodiment of a desired thermal gradient as represented by a thermal gradient profile. The graph shows a thermal gradient curve  20  as a function of a length  24  of a column of a gas chromatograph on an X axis, with temperature value being given on the Y axis. 
     The thermal gradient curve  20  may have several desired characteristics. A first characteristic of the thermal gradient curve  20  may be that the curve is monotonically non-increasing, also referred to as monotonically decreasing. This document defines monotonically non-increasing as shown in  FIG. 3  where the curve may include segments that are linear and non-increasing  30 , as well as segments that are decreasing  32 . However, this document also chooses to define the desired thermal gradient as “substantially” monotonically non-increasing as shown in  FIG. 4 . 
     To illustrate this concept,  FIG. 4  is provided as another illustration of the thermal gradient curve  20  that may be comprised of piece-wise or step-wise linear segments  40 . The step-wise linear segments  40  may be non-increasing as shown. The overall thermal gradient curve  20  is substantially monotonically non-increasing while also formed from a plurality of step-wise linear segments  40 . This figure is an example only and should not be considered limiting regarding the number or length of step-wise linear segments that may be used to form the thermal gradient curve  20 . 
       FIG. 4  also illustrates another feature of the first embodiment. The phrase “substantially monotonically non-increasing” is defined herein as a thermal gradient curve  20  that overall is monotonically non-increasing. However, there may be relatively short segments  44  in the thermal gradient curve  20 , relative to the entire length of the curve, that are increasing as shown within circle  42 . However, these short segments  44  that are increasing may be relatively short compared to the total length of the thermal gradient curve  20 , and therefore may not effect operation of the thermal gradient gas chromatograph. Accordingly, while the thermal gradient curve  20  may not be strictly monotonically non-increasing, by choosing to describe the curve as “substantially” monotonically non-increasing, this serves the purpose of allowing for short segments  44  that are actually increasing even though the overall thermal gradient curve  20  is decreasing. 
     What is important to this first embodiment is that the temperature generally or substantially decreases with distance when moving from the front end to the back end of the column. Nevertheless, the definition of the substantially monotonically non-increasing thermal gradient curve with a positive second derivative may also include exceptions where there are short segments or portions of the column where the temperature increases for a short length and where the second derivative of the thermal gradient curve may be strictly negative. Accordingly, the phrase “substantially monotonically non-increasing” may be used within this document to describe such a thermal gradient curve as well as a curve that has substantially a non-negative second derivative. 
       FIG. 5  is an example of a thermal gradient curve  20  that may be comprised of a combination of curving or arcuate segments  50  and step-wise linear segments  40 . This figure is an example only and should not be considered limiting regarding the number of arcuate segments  50  and step-wise linear segments  40  that may be part of the thermal gradient curve  20 . 
     It was stated earlier that the thermal gradient curve  20  may be defined as a curve that has a positive second derivative. The second derivative measures how the rate of change of a quantity is itself changing. On the graph of a function, the second derivative corresponds to the curvature of the graph. Accordingly, the second derivative of the thermal gradient curve  20  of the first embodiment may be positive. 
     Another feature of the first embodiment of the invention may be that the profile of the thermal gradient curve  20  may be raised or shifted upward while the defining characteristics of the thermal gradient curve  20  are not changed. For example, consider  FIG. 6  which shows the thermal gradient curve  20  in a first position  60  on the graph. Additional heat may then be applied to the entire column to cause a shift upward in the position of the thermal gradient curve  20  to a new position  62 . In effect, the thermal gradient curve may be translated upward with no other modification of its profile. 
     In other words, primary heat from a primary heat source has already been applied to the column to create the profile or shape of the thermal gradient curve  20 . This additional or secondary heat is applied from a secondary heat source at the same time as the primary heat. The effect of applying the secondary heat equally across the entire column may be to cause an upward shift of the entire thermal gradient curve  20  with or without changing the shape or profile. 
     It may be important that the secondary heat be applied in a systematic way. A systematic way includes but should not be considered as limited to a controlled application of the primary heat, the secondary heat or both in order to manipulate the profile of the thermal gradient. For example, the secondary heat may be controlled in order to modify a rate at which the secondary heat raises or shifts upward the profile of the thermal gradient. Control of the thermal gradient may be accomplished according to a pre-defined set of criteria. 
     The primary heat is applied to the column as different amounts of heat applied to different locations to thereby form the thermal gradient. The most heat is applied to the front end of the column, and then less and less heat is gradually applied to the column until reaching the back end. The primary heat may be applied as discrete segments that may result in a thermal gradient forming from a plurality of step-wise segments or linear segments. Alternatively, the primary heat may be applied with smaller discrete segments that may cause the thermal gradient to have a smooth or arcuate and not a step-wise or linear appearance. Alternatively, the primary heat may be applied to create a combination of arcuate segments and discrete step-wise or linear segments. 
     In contrast, the secondary heat may be substantially uniform along the entire length of the column. Accordingly, the thermal gradient curve  20  may be shifted upwards in temperature as shown in  FIG. 6 .  FIG. 6  shows an original position  60  without the secondary heat applied and the new position  62  of the thermal gradient curve  20  after the secondary heat is applied. The shift upwards of the thermal gradient curve  20  may be accomplished by any appropriate heating mechanism. 
     When it is time to detect compounds, the compounds are eluted from the column into a detector. This may be accomplished by raising the thermal gradient in the column in a systematic manner. It is believed that there may be advantages of systematic or programmed patterns of constructing and raising the thermal gradient within the column as the compounds are eluted. For example, as a compound is eluting from the column, a front edge of a peak may be at a lower temperature than a back end of the peak. This may cause the back end of the peak to have a velocity that is higher than the front end. A result of this difference in speed may be a compression of the peaks as they reach the end of the column. This may result in better separation of compounds because of narrower peaks, and increased sensitivity because the peaks may be higher and more symmetrical. 
     Another result of the first embodiment may be the preservation of the profile of the thermal gradient curve  20  as the compounds are moved through the column. In contrast, other prior art methods may destroy the thermal gradient by bringing the compounds in the column to an isothermal state or equilibrium. 
     It should be mentioned that the first embodiment may also be capable of being flexible in the profile of the thermal gradient curve  20 . In other words, while the profile of the thermal gradient may be shifted upwards by applying the secondary heat, substantially preserving the profile in the column, the thermal gradient in the column may also be modified, adjusted or otherwise changed without losing the characteristics of being substantially monotonically non-increasing and having a positive second derivative. Accordingly, it should be considered within the scope of the invention to allow for changes or modifications to the thermal gradient as it is held stationary or as it is raised by the secondary heat. 
       FIG. 7  is provided to illustrate one example of hardware that may be used for the column and heating sources that may be used to create the desired thermal gradient in a gas chromatograph of the invention.  FIG. 7  shows a first embodiment of a planar configuration for a column  70 . The column  70  may be formed in a planar configuration in order to enable uniform heating of the column  70 . 
     The column  70  may be formed in an appropriate material by forming a channel or column in a planar substrate material  72 , and then a covering or top layer  74  may be disposed over the planar substrate material as indicated by the dotted arrow. For example, the column  70  may be formed using etching, a laser, or any other means that may remove material from the planar substrate material  72 . 
     The length, width and depth of the column  70  may be manufactured using appropriate dimensions as understood by those skilled in the art. The length of the column  70  may be any desired length from 10 centimeters to 50 meters because the principles of the first embodiment are adaptable to different length columns. What may be important in this first embodiment is that the column  70  be disposed in the planar substrate material  72  so that a heating mechanism may then be disposed underneath, above, around, on a side or any other location that the heating mechanism may be disposed in order to uniformly heat the entire channel  70  when applying the secondary heat. For example, the heating mechanism may operate like a hot plate or an oven. However, this example should not be considered as limiting, and any heating method that will uniformly apply the secondary heat to the entire column  70  may be used and fall within the scope of the first embodiment. 
       FIG. 7  is provided as a perspective view of a portion of the GC and includes a first heating source  76  and a second heating source  78 . The first heating source  76  is shown disposed and underneath a front end  80  or injection end of the column  70 . The second heating source  78  is shown disposed underneath and along a length of the column  70 , including at the back end  82  or ejection end. The first heat source  76  may be considered to be the primary heat source that is used to create the thermal gradient within the column  70 . The secondary heat source  78  may be the secondary heat that is applied to the column to modify the thermal gradient once it is created. 
     The shape of the channel  70  in the planar substrate material  72  may be any desired shape including, but not limited to a spiral, a serpentine shape or any other shape that will provide a desired length of the column and enable the application of the primary heat in order to create the thermal gradient curve and application of the secondary heating if needed.  FIG. 7  shows that column  70  is formed as a serpentine shape in order to make the column as long as possible for the given width and length of the substrate material  72 . 
     The primary heat and the secondary heat may be applied to the column  70  using any prior art method including, but should not be considered as limited to a heat exchanger, an air bath oven, resistive heating, infra-red heating, inductive heating and microwave heating as understood by those skilled in the art. The examples of the first heating source  76  and the secondary heating source  78  are for illustration purposes only and should not be considered as limited by the figure. 
       FIG. 8  is provided as a perspective view and a profile view of a portion of the GC and includes a first heat source  96  and a second heating source  98 . The first heating source  96  is shown disposed and underneath a front end  100  or injection end of the column  90 , where the column begins at the center of a spiral. The second heating source  98  is shown disposed underneath and along a length of the column  90 , including at the back end  102  or ejection end. The first heat source  96  may be considered to be the primary heat source that is used to create the thermal gradient within the column  90 . The secondary heat source  98  may be the secondary heat that is applied to the column to modify the thermal gradient once it is created. 
     The shape of the channel  90  in the planar substrate material  92  may be any desired shape including, but not limited to a spiral, a serpentine shape or any other shape that will provide a desired length of the column and enable the application of the primary heat in order to create the thermal gradient curve and application of the secondary heating if needed.  FIG. 8  shows that column  90  is formed as a spiral shape in order to make the column as long as possible for the given shape of the substrate material  92 . 
     The column  90  may be formed in an appropriate material by forming a channel or column in the planar substrate material  92 , and then a covering or top layer  94  may be disposed over the planar substrate material as indicated by the dotted arrow. For example, the column  90  may be formed using etching, a laser, or any other means that may remove material from the planar substrate material  92 . 
     The manufacturing of the column in the substrate material may be performed using either macrofabrication or microfabrication technologies as is known to those skilled in the art. In other words, fabrication techniques may be applied from either or both macrofabrication and microfabrication technologies. 
     An aspect of the first embodiment may be the ability to use a column from the prior art. For example, previous columns in gas chromatographs include short column, long column, packed column and unpacked column designs. It should be understood that the first embodiment may be used with any of the prior art column designs to achieve the desired thermal gradient within the column. 
     Another aspect of the first embodiment is modification of the thermal gradient to alter either the rate at which the thermal gradient is shifted up or to make changes in the profile at different locations along the column. For example, such modifications to the profile may include changing a slope of the thermal gradient or changing the curvature, but other changes should also be considered to fall within the first embodiment of the invention. 
     Modifications of the thermal gradient may be designed to change one or more aspects of the GC including but not limited to resolution, efficiency, sharpness of the eluting peak or elution time. Such modifications may be done during a separation or in sequential separations. 
     A second embodiment of the present invention may be defined as a thermal gradient that is different from the thermal gradient of the first embodiment. However, the same thermal gradient GC may be used to create all the thermal gradients described in this document. 
     The thermal gradient of the second embodiment may be defined in terms a second thermal gradient being represented by a second thermal gradient curve  110  having a first section  112  that has a non-negative second derivative, and having a first derivative that is non-positive. Thus the first section  112  may appear as shown in  FIG. 9 .  FIG. 9  shows that the first section  112  may be linear and decreasing. The second section  114  of the second thermal gradient curve  110  may be flat or isothermal. 
     A third thermal gradient that is represented by a third thermal gradient curve. The third thermal gradient curve may have a first section that has a first derivative that is negative and a second section that has a non-negative second derivative. 
     Another aspect of the invention may be that as long as a thermal gradient exists over some portion of a column, then a thermal gradient exists that may provide the advantages of the present invention. The thermal gradient may be relatively small and may exist over a relatively short length of the column. The thermal gradient may be an arcuate slope, a linear slope or a step-wise function, or a combination of these profiles, and may be considered to be within the scope of the present invention. 
     These modifications of the thermal profile may be based on expected patterns of analytes in the sample, results of previous separations or real-time feedback of elution patterns in a current separation. Such feedback, either from previous runs of the GC, from statistical likelihood of a profile of analytes, or real-time closed loop feedback may be designed to improve estimates of retention time and quantitation as well as search for co-eluting contaminant peaks. 
     Those skilled in the art will readily appreciate that many modifications are possible in the example embodiments without materially departing from this first embodiment or the invention. Accordingly, all such modifications are intended to be included within the scope of this disclosure as defined in the following claims. It is the express intention of the applicant not to invoke 35 U.S.C. §112, paragraph 6 for any limitations of any of the claims herein, except for those in which the claim expressly uses the words ‘means for’ together with an associated function.