Gas separation: processes – Chromatography – With heating or cooling
Reexamination Certificate
2002-12-17
2004-03-16
Spitzer, Robert H. (Department: 1724)
Gas separation: processes
Chromatography
With heating or cooling
C095S089000, C096S102000, C096S105000
Reexamination Certificate
active
06706091
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates generally to chemical separations in microanalytical systems and, more particularly, to sub- to super-ambient temperature programming of a microfabricated gas chromatography column for efficient separation of high volatility analytes.
Portable, handheld microanalytical systems, which have been termed “chemical laboratories on a chip,” are being developed to enable the rapid and sensitive detection of particular chemicals, including pollutants, high explosives, and chemical and biological warfare agents. These microanalytical systems should provide a high chemical selectivity to discriminate against potential background interferents and the ability to perform the chemical analysis on a short time scale. In addition, low electrical power consumption is needed for prolonged field use. See, e.g., Frye-Mason et al., “Hand-Held Miniature Chemical Analysis System (&mgr;ChemLab) for Detection of Trace Concentrations of Gas Phase Analytes,”
Micro Total Analysis Systems
2000, 229 (2000).
Current gas-phase microanalytical systems are based on gas chromatography (GC). Gas chromatography relies upon the chemical equilibria of analytes between a mobile phase and a stationary phase in a GC column to bring about a temporal separation of analytes in a gas mixture. Chemical equilibria and, therefore, column retention times are strongly influenced by column temperature. Thus, column temperature must be accurately controlled to obtain precise and reproducible separations.
The goal of a GC analysis is normally to obtain a separation with the required precision in the minimum time. Isothermal operation of the GC column can have drawbacks for achieving this goal with certain gas mixtures. If the selected isothermal temperature is too low, early eluted peaks may be adequately spaced but more strongly retained analytes will have broad and low-lying peaks with consequent poor detectability. This may also result in unacceptably long elution times. Conversely, the more strongly retained analytes will elute faster at a higher isothermal column temperature, but at the expense of poorer separation and loss of resolution for the early eluting analytes.
This general elution problem may be solved by temperature programming of the column. With temperature programming, analysis time can be reduced and the overall detectability of components can be improved. For example, for a given column it is possible to analyze gas mixtures with a broader volatility range in a shorter analysis time with temperature programming. For most analytes, the baseline resolution and peak widths are also improved. In general, temperature programming can comprise a series of changes in the column temperature that can include isothermal and controlled temperature rise segments. As an example of temperature programming, consider temperature ramping. Temperature ramping comprises monotonically increasing the temperature as the gas mixture is passed through the column. Higher volatility analytes in the mixture, which without temperature ramping pass through the column the earliest, still are the first to arrive at the column exit. Temperature ramping only tends to modestly improve the peak widths of these early eluting analytes and enhances baseline resolution somewhat. This is mainly due to the fact that these faster eluting analytes pass through the column before the initial temperature is appreciably increased. On the other hand, less volatile analytes, which in the absence of ramping tend to elute slowly with relatively broad and low-lying peaks, elute more quickly with temperature ramping and peak shapes are generally improved from the standpoint of baseline resolution and peak width. As a result, analysis time can be improved relative to a low temperature, isothermal elution while retaining peak resolution.
In conventional chromatography, an oven enclosing the GC column is used to effect the temperature program. This process is energy intensive, requiring hundreds of watts of power, and is capable of providing only modest ramp rates of about 25° C./min. These characteristics are adequate for laboratory applications where power is not that limited, and long, 30-meter columns can be used to separate difficult mixtures without the need for faster ramp rates. However, for portable applications, this level of power consumption is unacceptable. In addition, most conventional chromatographs only provide super-ambient temperature ramping. Given the necessarily shorter length of portable GC columns relative to laboratory instruments, sub-ambient and more rapid temperature ramping can compensate for the loss of resolution due to fewer theoretical plates in the portable GC column.
A temperature-controlled liquid chromatography column is disclosed in U.S. Pat. No. 4,534,941 to Stephens et al. That invention uses a plurality of thermoelectric modules to control the temperature of a long, tubular chromatographic column. The GC column is mounted on a notched side of a long thermal block and the plurality of thermoelectric modules are attached to the other, flat-surfaced side of the thermal block. Each thermoelectric module is attached to a separate heat sink that is actively cooled by airflow drawn through a plenum by a fan. Therefore, individual control of each of the plurality of thermoelectric modules is required to obtain adequate control of the column temperature. Because of the large thermal mass of this chromatography system, heating rates are limited to 12°-15° C. per minute. Further, the large system is not suitable to portable, handheld microanalytical systems.
A temperature programmable microfabricated gas chromatography (&mgr;GC) column has been disclosed in U.S. patent application Ser. No. 10/061,383, to Manginell and Frye-Mason, which is incorporated herein by reference. However, that &mgr;GC column was integrated with a resistive heating element, providing only super-ambient temperature ramping. Adequate separation of low-boiling-point, volatile compounds is difficult with such a super-ambient column.
The present invention solves the need for a sub- to super-ambient temperature programmable microfabricated GC column through the use of a thermoelectric cooler with temperature sensing on a microfabricated GC column. The present invention permits rapid, low-power and sensitive temperature programming of the microfabricated GC column with temperature ramping from sub-ambient temperatures that are an order of magnitude faster than conventional GC columns, thereby enabling more efficient separation of volatile compounds.
SUMMARY OF THE INVENTION
The present invention comprises a temperature programmable microfabricated gas chromatography column comprising a substrate, a channel etched in the substrate to separate chemical aralytes in a gas mixture, means for sealing the channel, and at least one thermoelectric cooler disposed on at least one surface of the substrate to heat the column from sub-ambient temperatures during the separation. The temperature programmable microfabricated gas chromatography column can further comprise a temperature sensor and a control board for electrical control of the thermoelectric cooler and fluidic control of, the column.
The present invention further comprises a method for separating a plurality of chemical analytes in a gas mixture, comprising cooling a temperature programmable microfabricated gas chromatography column to a sub-ambient temperature with a thermoelectric cooler, and injecting the gas mixture into the temperature programmable microfabricated gas chromatography column to separate the plurality of chemical analytes in the gas mixture. The method further comprises heating the column from a sub-ambient temperature to a higher temperature after injecting the gas mixture.
REFERENCES:
patent: 3149941 (1964-09-01), Barnitz et al.
patent: 3630006 (1971-12-01), Sandoval
patent: 4350586 (1982-09-01), Conlon et al.
patent: 4534941 (1985-08-01), Stephens et al.
patent: 5151110 (1992-09-01), Bein et al.
patent: 5165292 (1992-11-01), Prohaska
pat
Anderson Lawrence F.
Robinson Alex L.
Bieg Kevin W.
Sandia Corporation
Spitzer Robert H.
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