Method and apparatus for microwave assisted chemical reactions

A method of microwave assisted chemical reaction includes providing a microwavable reaction vessel which contains at least one material in a sample. The sample is heated by microwave energy to elevate the temperature of the reagent and at least partially volatilize the sample to establish a gas phase within the vessel followed by positive cooling of the gas phase to reduce the temperature and responsively reduce the pressure of the gas phase without effecting substantial cooling of the liquid phase. The method may involve employing cooling exteriorly of and adjacent to the gas phase containing portion of the vessel or cooling by means of a coolant flowing within coils disposed in the interior of the vessel or both. The process is preferably a continuous process. The apparatus may be a vessel transparent to microwave energy for receiving the sample. The vessel has space overlying the liquid phase containing portion for a gas phase. Structures for cooling means for positively cooling the gas phase to reduce the pressure of the gas phase without effecting substantial cooling of the reagent are provided. These structures for cooling may be contained within the vessel, exteriorly of the vessel or modification of the vessel configuration to facilitate gas phase cooling or combinations thereof.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to a method of microwave assisted chemical 
reactions, such as sample preparation, synthesis, derivatization or 
extraction which involves reduced pressure within the vessel and 
associated apparatus for accomplishing this objective. 
2. Description of the Prior Art 
The use of microwave energy in analytical chemistry to provide heat to 
assist chemical reactions has been known for approximately 15 years. See, 
generally, Mingos et al., Applications of Microwave Dielectric Heating 
Effects to Synthetic Problems in Chemistry, Chem. Soc. Rev. 1991, 20, pp. 
1-47. 
It has been known to employ such microwave heating in sample preparation. 
See, Kingston et al., Comparison of Microwave Versus Conventional 
Dissolution of Environmental Applications, Spectroscopy 7 (9) 
November/December 1992, pp. 20-27. One approach involves an open-vessel 
approach in which the result is achieved with the assist of microwave 
heating. An alternate approach is the so called "closed-vessel" microwave 
sample preparation. 
It has been know to use microwave energy for various types of environmental 
processes. For example, microwave energy, such as that produced by a 
nominal or high intensity microwave oven, has been employed to extract 
pesticides from sediment samples. See, Onuska et al., Extraction of 
Pesticides from Sediments Using a Microwave Technique, Chromatographia, 
Vol. 36, pp. 191-194 (1993). Microwave heating has also been employed in 
effecting hydrolysis of proteins. See, Margolis et al., The Hydrolysis of 
Proteins by Microwave Energy, Journal of Automatic Chemistry, Vol. 13, No. 
3, pp. 93-95 (May/June 1991). 
It has also been known to employ microwave energy in a closed vessel 
digestion system wherein a closed Teflon PFA vessel has an organic sample, 
an inorganic sample or a combination subjected to acid decomposition under 
the influence of microwave energy. See, Kingston et al., Microwave Energy 
for Acid Decomposition at Elevated Temperatures and Pressures Using 
Biological and Botanical Samples, Anal. Chem., 58, pp. 2534-2541, 
(October, 1986). 
In such closed vessel microwave sample preparation techniques, typically, 
one or more materials which will become the sample are mixed or dissolved 
in a suitable liquid reagent. The liquid reagent occupies a portion of the 
volume of the relatively small vessel and is subjected to chemical 
alteration under the influence of the microwave heating, thereby creating 
a gas phase in addition to the liquid phase within the vessel. The 
microwave heating results in increased temperatures and pressures within 
the vessel which can present a potential safety hazard through vessel 
failure. The increased temperature is required for advancement of the 
reaction rate, but the pressure is a property of the heat flow 
characteristics of the vessel and microwave interaction. 
It has been known to control heat loss from the vessel by providing a 
jacket of thermal insulation around the vessel which also acts to 
strengthen the vessel. See, generally, Mingos et al., Applications of 
Microwave Dielectric Heating Effects to Synthetic Problems in Chemistry, 
Chem. Soc. Rev., 1991, 20, pp. 1-47 and Chapter 6, Introduction to 
Microwave Sample Preparation Theory and Practice by Kingston et al., 
American Chemical Society, 1988, pp. 93-154. 
U.S. Pat. No. 5,215,715 discloses a method of digesting materials which are 
dispersed in an acid digesting medium, which dispersion is subjected to 
microwave heating in a first chamber and then both the gas and liquid 
phases of the dispersion are cooled in another chamber. There is no 
segregated cooling of the gas phase while heating the liquid phase. There 
is also no recognition of the pressure relationship between the gas phase 
and liquid phase during microwave radiation. 
In prior art practices, pressure within the vessel has been permitted to 
form at whatever natural level occurred due to the specific reagents, 
temperature, reaction products, microwave interaction and heat flow of the 
vessel. 
There remains, therefore, a very real and substantial need for a more 
efficient and safe means of microwave sample preparation in a closed 
vessel. 
SUMMARY OF THE INVENTION 
The present invention has solved the above-described problems by providing 
a method and apparatus wherein a microwavable reaction vessel is provided 
with a liquid reagent mixture and/or sample. For convenience of reference 
herein, both of these categories and any similar materials to be processed 
will be referred to as a "sample." The sample is heated so as to elevate 
the temperature thereof to establish at least partial volatization of the 
sample and thereby create a gas phase overlying the liquid reagent within 
the vessel. The gas phase is positively cooled to reduce the temperature 
in the gas phase and, responsive to said temperature reduction, reducing 
the pressure without effecting substantial cooling of the liquid reagent. 
The cooling of the gas phase may be effected by providing channels for 
coolant flow exteriorly of the vessel or coolant flow within the vessel 
within coils or both. In this manner, the temperature and pressure of the 
gas phase are reduced in the preferred practice of the invention, while 
the coolant flowing in the cooling conduits, whether they are disposed 
interiorly or exteriorly of the vessel or both, does not directly cool the 
liquid reagent. 
The apparatus for practicing the method preferably includes a vessel, such 
as a vessel or vessel liner made from a suitable polymer or fluoropolymer, 
such as polytetrafluoroethylene, TFM or perfluoroalkoxy, which is 
transparent to microwave energy and receives the liquid reagent mixture 
and/or sample. The vessel may also utilize an outer casing of a different 
material, such as polyetherimide, glass filled polyetherimide, and other 
suitable materials. The vessel has additional capacity for the gas phase. 
Cooling means provide for positive cooling of the gas phase to reduce the 
temperature and pressure of the gas phase. The cooling means has 
passageways for the flow of coolant. The passageways may be disposed 
exteriorly of the vessel and adjacent to the outer walls of the vessel 
with the passageways not being disposed adjacent to the sample or liquid 
reagent containing portion of the vessel. In another embodiment, the 
passageways are coils disposed within the gas phase portion of the vessel. 
It is an object of the present invention to provide a method and apparatus 
for closed vessel microwave assisted chemical reactions which effectively 
reduces the pressure in the gas phase within the vessel. 
It is another object of the invention to provide such a system wherein the 
pressure reduction in the gas phase is effected through positive cooling 
to reduce the temperature thereof. 
It is another object of the present invention to provide such a system 
which may be employed in microwave digestion and reaction bombs. 
It is a further object of the present invention to provide such a system 
which is employed in preparing chemical samples for later analysis. 
It is a further object of the invention which permits microwave heating of 
the sample to elevate its temperature simultaneous with positive cooling 
of the gas phase. 
It is yet another object of the invention to provide such a system which is 
adapted to accomplish sample preparation in a much more rapid manner than 
those previously known. 
It is a further object of the present invention to provide such a system 
which will contribute to increased durability of the vessels. 
These and other objects of the invention will be more fully understood from 
the following description of the invention on reference to the 
illustrations appended hereto.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Microwave vessels employed in chemical reactions, such as sample 
preparation, synthesis, derivatization and extraction generally are of 
relatively moderate size and may have an interior volume of about 1 mL to 
500 mL and preferably in the range of about 1 mL to 125 mL. The vessels 
may have any desired configuration, but are frequently generally 
cylindrical in shape. They may be made of Teflon (tetrafluoroethylene, PFA 
or TFM or PTFE) or other fluorinated carbon plastics with a removable lid 
adapted to seal in place as by threaded or pressure fitted securement to 
maintain the desired amount of pressure, which for this type vessel, might 
be in the order of up to about 10 atmospheres. Another type of vessel 
would have a plastic casing for rigidness and pressure stability with a 
Teflon, plastic or quartz liner for chemical inertness and be adapted to 
withstand pressures of about 5 to 20 atmospheres. In this latter category, 
the vessel may be designed so as to withstand pressures of 40 to 100 
atmospheres. 
Closed vessel digestion will generally achieve higher temperatures because 
the boiling point of the reagent is raised by the pressure produced within 
the vessel. The higher temperature in the closed vessel will, however, 
greatly reduce the time required for reaction. The closed vessel also 
resists evaporation and there is, therefore, no need to add reagent to 
maintain the desired volume. 
The vessels are effectively transparent to microwave energy so as to permit 
them to be introduced into a microwave oven and the reagents and samples 
contained in them to be heated to the desired temperature. As the liquid 
reagent containing one or more materials is heated, a gas phase is formed 
through the vaporization of the solvent and/or the chemical materials. The 
sample or samples will generally be mixed with a liquid reagent which may, 
for example, be nitric acid employed in microwave-heated digestions. In 
order to maintain pressure levels within the desired ranges of safety and 
contribute to durability of the vessels, as well as achieving the desired 
temperature which is most beneficial for the chemical reaction 
contemplated, the present invention provides positive cooling to the gas 
phase contained within the vessel while resisting effecting meaningful 
cooling of the liquid reagent. 
For a given liquid reagent, the absorption of microwave energy can be 
calculated at a specific frequency employing Equation 1. 
##EQU1## 
wherein: P=is the apparent power absorbed by the sample in watts (W), 
(W=joules/sec); 
K=is the conversion factor for thermochemical calories/sec to W, which is 
4.184; 
C.sub.p =is the heat capacity, thermal capacity, or specific heat 
(cal./g..DELTA.C); 
m=is the mass of the sample in grams (g); 
.DELTA.T=is T.sub.f, the final temperature minus T.sub.i, the initial 
temperature (.DELTA.C); and 
t=is the time in seconds (s). 
##EQU2## 
In the event that no energy is permitted to escape from the vessel, the 
final temperature can be determined by equation 2. 
As shown in Equation 3, a lower temperature is achieved if energy is 
permitted to escape. This escape can be primarily from the gas phase as it 
has the greatest area of cool vessel wall to contact. 
In the present invention, active cooling of the gas phase serves to reduce 
the gas phase pressure. If desired, the microwave energy applied to the 
liquid phase sample may be increased to compensate for the thermal energy 
losses to the gas phase. 
Referring now more specifically to FIG. 1 wherein there is shown a closed 
microwave reaction vessel which may be adapted for use with automation or 
a robot as distinguished from individual human handling, if desired. There 
is shown a vessel consisting of a liner 2 which may be composed of a 
suitable fluorinated carbon plastic, such as tetrafluoroethylene which is 
sold under the trade designation "Teflon" or other material having 
suitable strength, microwave transparency, and chemical inertness. The 
vessel liner 2 has a threaded closure 4 intimately secured in sealing 
relationship to the liner 2. The closure 4, in the form shown, has a pair 
of upwardly projecting, threadedly secured port defining members 5, 6 to 
which apertured closures 7, 8, respectively, are secured. While these port 
closures 7, 8 may be closed off if desired, in the illustrated embodiment 
temperature probes 10, 12, respectively, extend into the vessel 2 to 
different depths. These probes 10, 12 may be of any conventional type and 
are sealingly secured to the port closures 7, 8. 
Positioned in surrounding relationship with respect to liner 2 is an outer 
wall or casement 20 which is in intimate surface-to-surface contact with 
the exterior of the vessel 2 and closure 4. The casement 20 may be 
provided in multiple pieces (not shown) assembled around the vessel by any 
desired means known to those skilled in the art. The vessel 2, closure 4, 
and outer wall 20 are preferably of generally cylindrical configuration. 
The outer wall or casing 20 has an inwardly open continuous helical groove 
22 which cooperates with exterior of the vessel liner 2 and closure 4 to 
create a continuous coolant flow passageway. The passageway is spaced 
(measured along the vessel longitudinal axis) from the sample liquid 
reagent received portion 30 of the vessel. A coolant entry channel 24 is 
defined within casement 20 and is in communication with passageway 22. 
Coolant is discharged through exit channel 26. The coolant will preferably 
be captured as it emerges from channel 26 and subjected to a heat 
exchanging temperature reduction after which it may be reintroduced into 
coolant entry channel for another cycle of operation. The coolant may be 
microwave non-absorbing, moderately absorbing, or strongly absorbing 
material that may be in a gas or a liquid phase. 
If desired, the coolant passageways may be provided in other ways. For 
example, such as by a single ring, which is inwardly open to provide an 
annular passageway in cooperation with or adjacent to the exterior of the 
vessel. Also, an axially elongated single ring or a plurality of such 
rings either interconnected or individually supplied with coolant may be 
employed. 
Referring now to FIG. 2 in greater detail there is shown a microwavable 
vessel 40 having threadedly and sealingly secured thereto a closure 42 
which has a pair of externally threaded ports 44, 46 to which are secured 
threaded sealing closures 48, 50 respectively. The liquid reagent mixture 
or sample 54 is contained within the lower portion of the vessel interior 
and the gas phase 56 appears thereabove. A coolant coil 60 is received 
within the interior vessel 40 and has an entry end 62 and a discharge end 
64. In effecting cooling of the gas phase 56 without effecting substantial 
cooling of the liquid reagent mixture 54, coolant is permitted to flow 
into entry 62, assume a heat exchanging interaction with the gas phase and 
then emerge at an elevated temperature at discharge end 64. The coolant 
coming out of end 64 is subsequently subjected to a heat exchanging 
process wherein the temperature of the coolant is reduced after which the 
coolant is reintroduced through entry 62. It will be appreciated that, in 
this manner, continuous cooling of the gas phase will be effected to 
thereby reduce the pressure within the gas phase 56. If desired, coils of 
additional length or multiple coils having separate entries may be 
employed. If desired, radiator structures may be employed in the vessel 
interior in lieu of the coil or coils. 
It will be appreciated that the embodiment shown in FIGS. 1 and 2 are not 
mutually exclusive and that the coil or coils employed in connection with 
the embodiment of FIG. 2 may be employed in addition to the passageway 
containing outer wall 24 of FIG. 1 in order to achieve the desired degree 
of temperature reduction of the gas phase and corresponding reduction of 
pressure in the vessel interior. 
The partial traditional equilibrium pressures and the partial pressures of 
the reagents and sample and reaction byproducts do not hold in this system 
as equilibrium of temperature between liquid and gas phases is never 
reached. Condensation of several components may occur reducing the partial 
pressure of one or more thus reducing the total pressure in the vessel. A 
dynamic nonequilibrium condition is established that is unique to 
microwave reagent closed vessel systems such as these and is a new 
relationship that is being employed to produce these new reaction 
conditions. 
Referring now to FIG. 3, there is shown schematically a block diagram of a 
continuous or semi-continuous flow system of the present invention. The 
gas phase portion of vessel 80 receives coolant through pipe 82 by means 
of pump 84. After the coolant absorbs heat from the gas phase contained 
within vessel 80, the elevated temperature coolant emerges through pipe 90 
and enters heat exchanger 92 wherein heat is withdrawn and the coolant is 
reduced to a temperature desired for introduction into the gas portion of 
vessel 80. The reduced temperature coolant emerges from the heat exchanger 
92 and is carried by pipe 94 to pump 84 for reintroduction into vessel 80. 
Referring to FIG. 4, there is shown a plot of temperature in degrees 
centigrade and pressure in atmospheres as related to time. It compares a 
thermally insulated vessel with a thermally uninsulated vessel, i.e., a 
Teflon vessel. The difference in pressure inside the vessels is due to the 
loss of thermal energy in the gas phase. For example, the pressure of 6* 
10 mL of concentrated nitric acid irradiated at 574 watts for 10 minutes 
at 180.degree. C. is about 40 psi in the insulated vessel and is only 
about 8 psi in the uninsulated vessel. The absorption of microwave energy 
which can be calculated from equation 1 is the same for a given liquid. 
EXAMPLE 
In order to enhance the understanding of the invention, an example will be 
provided. A closed microwave vessel having an interior volume of 120 mL is 
provided with 20 mL of nitric acid mixed with a 0.5 gram liver tissue 
(material) in a closed vessel acid digestion process. The vessel was 
exposed to 500 watts of microwave energy for a period of 10 minutes to 
establish a liquid temperature of 190.degree. C. and a liquid partial 
pressure inside the vessel of 620 psi without cooling. When a similar 
situation is constructed with cooling of the gas phase, there was 
established a pressure with the acid and digestion products of 120 psi 
inside the vessel. This demonstrates positive cooling by a method of the 
present invention employing a method of air coolant to produce after 10 
minutes a gas phase temperature of 130.degree. C. and a gas phase partial 
pressure of 120 psi without effecting a substantial reduction in the 
liquid phase temperature. A 650 watt power was applied in the second 
example to maintain the liquid temperature at 190.degree. C. As a result, 
the acid digestion was effected while reducing the vessel pressure by 500 
psi. 
The coolant may be a gas or liquid with or without entrained solids, and is 
preferably transparent to microwave energy. Among the preferred coolant, 
materials are one or more materials selected from the group consisting of 
air, CO.sub.2, freon, gaseous N.sub.2 and liquid N.sub.2. 
The system of the present invention builds upon and enhances certain 
scientific principles as applied to solve a particular problem. The unique 
nature of microwave interaction and two distinct heat transfer mechanisms 
permits the cooling of the gas phase while continuing to heat the liquid 
phase. Heating a liquid in a microwave field is commonly referred to as 
dielectric loss. The two primary mechanisms are dipole rotation and ionic 
conduction. See, generally, Kingston, H. M. and Jassle, L. B., Eds., 
"Introduction to Microwave Sample Preparation: Theory and Practice," ACS 
Professional Reference Book, American Chemical Society, Washington, D.C., 
1988, pp. 9-15. Ionic conduction is the conductive migration of dissolved 
ions in the applied electromagnetic field. Dipole rotation is the 
alignment, due to the electric field, of molecules that have permanent or 
induced dipole moments. When a molecule vaporizes and is converted to the 
gas phase, from the liquid phase, charged ions are left in the liquid 
phase, thereby eliminating this heating mechanism. In addition, rotation 
of the molecule in the gas phase does not efficiently transfer heat, as 
rotation without collision, does not add heat to the gas phase. Gas 
molecules frequently collide with the surfaces of the vessel. These 
surfaces are not heated by microwave energy and are actively cooled, 
thereby cooling the gas phase. The vessel is generally made of a material 
which is usually essentially microwave transparent. The gas phase is not 
efficiently heated by the microwave field even though the gas phase and 
liquid phase both exist in the same microwave field. These heating 
conditions are unique to the microwave environment. The present invention 
employs the ability to cool the gas phase while continuing to heat the 
liquid phase in this environment. The present invention involves 
intentionally cooling the gas phase while heating the liquid phase to 
effect the reduction of the internal vessel pressure while maintaining a 
relatively high liquid temperature in which various chemical reactions are 
conducted. 
It will be appreciated, therefore, that the present invention provides a 
method and apparatus for pressure control and reduction in 
microwave-assisted chemical reaction systems. This is accomplished through 
positive cooling of the gas phase which is in contact with the liquid 
phase in the chemical reaction vessels without effecting significant 
reduction in temperature of the liquid phase. The positive cooling of the 
gas phase facilitates corresponding pressure control of the gas phase in 
order to achieve the desired chemical or physical parameters during and 
following the reaction period. The reactions in the liquid phase can, 
therefore, be carried out without undesired interference as a result of 
the positive cooling of the gas phase. The practice of the present 
invention will generally reduce the pressure in the gas phase about 50 to 
95 percent and preferably about 60 to 90 percent. If desired, positive 
cooling action may be terminated or regulated when the desired gas phase 
pressure has been attained. 
It will be appreciated that the present invention permits efficient 
thermally activated chemical reactions to occur at the desired 
temperature, while facilitating a reduction in pressure within the vessel 
at that temperature. This facilitates improved process efficiency, safety 
and durability. Improvement of the durability of the vessel is achieved 
through maintaining the integrity by resisting overheating of the casing 
in double walled vessels. Also, in the embodiment of FIG. 1, the coolant 
may serve to carry away sample or reaction products that might become 
trapped between the outer wall 20 and the vessel liner 2. 
Also, if desired, the vessel might be formed with partially hollow 
outwardly projecting fins or ribs to facilitate radiation loss of heat 
from the gas phase. In the alternative, multi-walled vent openings may be 
provided in the outer wall to enhance cooling of the gas phase. 
A plurality of circumferentially spaced, axially oriented ribs may be 
provided within the gas phase region of the vessel, but not in the liquid 
phase portion. such a construction will be deemed positive cooling within 
the context of the present invention. 
In addition to the foregoing the turntable onto which the vessel is placed 
may be cooled. The hollow turntable top might have a recess which receives 
an upper portion of the vessel in intimate contact therewith. Coolant may 
be circulated within the hollow turntable top. 
While not the preferred practice of the invention, if desired, gas may be 
withdrawn from the gas phase of the vessel, cooled and subsequently 
returned to the gas phase of the vessel. 
The vessel may be a container that holds volumes from about 50 mL to 500 mL 
or may be an elongated tube which is closed to the atmosphere and in which 
the sample flows through the microwave field. 
An elongated tube may have the sample and gas phase moving by the microwave 
source and cooling means so as to permit both heating of the sample and 
cooling of the gas phase which would be present in the sealed tube. As 
this embodiment would involve commingling of the liquid sample and gas 
phase, it is not the preferred embodiment. 
It will be appreciated that the present invention may be employed 
advantageously with a wide variety of materials and end uses. The 
following examples will illustrate some advantageous uses. Among the 
specific end uses for which the sample preparation, method and apparatus 
of the present invention may be employed are microwave assisted 
decomposition, synthesis, derivatization and/or extraction or leaching. 
The invention may be employed to perform mineral acid decompositions while 
cooling the acid vapor to reduce the temperature and responsively the 
pressure of the decomposition system. Also, organic extraction with 
organic solvents may be performed while cooling the gas phase to reduce 
the pressure of the overall reaction. 
The invention may be employed to perform organic or inorganic synthesis 
with solvents while cooling the gas phase to reduce the pressure during 
synthesis. 
The invention may also be employed to perform hydrolysis on a protein with 
a solvent mixture including hydrochloric acid and cooling the gas phase to 
effect a reduction in pressure during hydrolysis. Another use is drying to 
condense components of the vapor phase. 
In some instances, the gas phase may be cooled to resist temperature damage 
to the material out of which the inner liner or outer casings are made, 
such as polyetherimide, for example. The invention may also be employed 
with azeatropes, as well as aqueous materials. 
Uses in environmental, biological, medical and industrial fields will be 
readily apparent to those skilled in the art. 
The invention may be employed with all types of microwave systems 
including, for example, cavity-type microwave systems, focused microwave 
systems, flow and stop flow microwave systems, and antenna transmitted 
microwave cavities. 
With respect to the liquid temperature, if desired, one may operate at a 
higher liquid temperature with no increase in vessel internal pressure or 
at similar liquid temperatures with a decrease in pressure. 
The invention further facilitates resisting undesired escape of the 
volatile elements, molecules, and compound losses when opening vessels to 
the atmosphere and condensing of these from the gas phase. 
Whereas particular embodiments of the invention have been described herein 
for purpose of illustration, it will be evident to those skilled in the 
art that numerous variations of the details may be made without departing 
from the invention as defined in the appended claims.