WO2000023795A1

WO2000023795A1 - Environmentally controllable sample holder for x-ray diffractometer (xrd)

Info

Publication number: WO2000023795A1
Application number: PCT/US1999/024678
Authority: WO
Inventors: Charles Amick Buckner, Iii; William Christopher Kidd, Iii; Peter Gregory Varlashkin
Original assignee: Glaxo Group Ltd
Current assignee: Glaxo Group Ltd
Priority date: 1998-10-21
Filing date: 1999-10-21
Publication date: 2000-04-27
Anticipated expiration: 2001-04-21
Also published as: AU1129500A; WO2000023795A9

Abstract

An environmentally controllable sample holder for use with the sample changer (SC) of an X-ray diffractometer includes a sample holder (10) comprising a sample plate (24), a base (12) that can be removably attached to the sample changer, a heating element (14) positioned between the base and the sample plate, and a temperature sensor (TS) adapted to provide a feedback signal for use to control the temperature of the heating element. A housing (40) is provided for sealing enclosing the sample holder wherein the housing has an aperture (A) in the bottom thereof for sealing receiving the sample holder therein, and air inlet (42A) and air exit (42B) nozzles for introducing and exhausting gasses from the housing. A thermocouple (44) is provided in the housing, and the top portion (46) of the housing is formed from an X-ray transparent material.

Description

ENVIRONMENTALLY CONTROLLABLE

SAMPLE HOLDER FOR X-RAY DIFFRACTOMETER (XRD)

Technical Field

The present invention relates to the analysis of substances using electromagnetic radiation, and more particularly to an improved

environmentally controllable sample holder for use with an X-ray diffractometer (XRD).

Related Art As is well known to those skilled in the art, X-ray diffractometry is a

technique for performing physical and chemical analysis of crystalline

substances. In X-ray diffraction, the crystallites of the crystalline substance act in relation to X-rays in an equivalent manner as a diffraction grating acts in relation to visible light. Each unit cell of which a crystalline structure is composed acts as a diffraction center. The radiation intensity at a point

removed from the crystalline structure is determined by the phase difference and intensity of radiation diffracted from each diffraction center to the point in question. A diffracted X-ray beam is essentially a collection of a large number of scattered X-ray waves that satisfy the conditions of constructive interference. During X-ray diffractometry analysis, the sample is irradiated with an X- ray beam produced by an X-ray source and incident at an angle. The X-rays diffracted by the powder sample held in the sample holder are detected by a detector positioned at a diffracted angle equal to the incident angle. The

incident angle and hence the diffracted angle are incrementally varied as both the X-ray source and the detector move along a semi-circle above the sample and sample holder. The movements are synchronized so that the incident angle and the diffraction angle are always equal. The X-ray diffractometer

records a diffractogram, which is the intensity of the diffracted X-ray as a

function of angle. The powder sample can be identified based on its diffractogram.

There are several disadvantages or shortcomings suffered by most

commercially available sample holders for use with an X-ray diffractometer

(XRD). First of all, the sample is exposed to air. A typical X-ray diffraction

analysis may require from a few minutes to a few hours. To improve the signal-

to-noise ratio of the detected signal, a large number of scans may be co-added to create an average diffraction pattern. In addition, signal-to-noise may be

improved by obtaining the diffraction pattern at a slower scan rate. Air or

moisture sensitive samples may be destroyed (chemically altered) during the analysis. One manner in which to protect the sample is to cover the sample with a metal or plastic film thin enough to allow the X-ray beam to pass through.

The problem with this approach is that the film is also in the sampling point of

the diffractometer. That is, X-rays diffracted by the sample cover will be detected by the X-ray detector. As a result, the background signal arising from the cover film cannot be distinguished from the signal of the sample. Another disadvantage is that most commonly available sample holders

are fixed volume. Different sample holders must be used for samples of

different size in order to achieve the best signal-to-noise ratio. To handle small samples, a sample holder with a small depression or flat plate with the sample applied in a thin surface coating is necessary. To minimize background signal,

the sample holder should be made of a low background material such as single crystal quartz or silicon.

Particularly pertinent to applicants' invention, conventional environmentally controllable sample holders for diffraction analysis are inconvenient to use when multiple users in both routine (ambient environment)

and non-routine (non-ambient temperatures and relative humidities) modes are using an X-ray diffractometer (XRD). However, environmentally controllable

sample holders must be utilized from time to time in order to subject powder

drug samples to X-ray diffraction at ambient and non-ambient conditions so as

to aid a pharmaceutical company or the like to develop proper data regarding the physical behavior of drugs. As is well known to those skilled in the art,

conventional X-ray diffractometer (XRD) devices provide complex environmentally controlled sample stages or holders for obtaining X-ray diffractograms under non-ambient conditions (e.g., elevated and sub-ambient

temperatures). The use of these environmentally controlled sample stages or holders requires removal of the XRD sample changer, followed by installation and alignment of the environmentally controlled sample stage. To return to a routine operation mode of the XRD, it is then required to remove the environmentally controlled sample stage and re-install and re-align the sample changer of the XRD. These instrumental manipulations do not provide any- significant problems for dedicated expert users, but are extremely time consuming and beyond the skill level of many routine users of an XRD. Accordingly, what is needed is an improved, environmentally controlled sample holder for an X-ray diffractometer (XRD) that fits directly onto the XRD sample changer and that does not require any instrument re-alignment so that

users skilled in routine operation of the XRD but not skilled in sample stage alignment procedures can quickly set up the novel environmentally controlled

sample holder for non-ambient analysis (e.g., a scan at elevated temperatures) and then quickly return the instrument to a routine mode for subsequent users.

Applicants have discovered such an improved environmentally controlled sample holder for use with the conventional sample changer of an X-ray diffractometer.

Disclosure of the Invention

The present invention provides an environmentally controllable sample holder for use in combination with the sample changer of an X-ray diffractometer (XRD). The sample holder comprises a sample holder including a sample plate, a base adapted for removable attachment to the sample changer, a heating element positioned between the sample plate and the sample holder base, and a temperature sensor adapted to provide a feedback

signal for use in controlling the temperature of the heating element. A detachable housing is provided for sealingly enclosing the sample holder

wherein the housing includes an aperture in the bottom for sealingly receiving the sample holder therein and air inlet and air exit nozzles for introducing and exhausting gases from the housing. A temperature sensor is mounted in the 5 housing in order to measure the temperature therein, and the housing includes an X-ray transparent top portion or window therein.

It is therefore an object of the present invention to provide an improved

environmentally controllable sample holder for an X-ray diffractometer (XRD).

It is another object of the present invention to provide an

o environmentally controllable sample holder for convenient operation with an X- ray diffractometer (XRD) by multiple users in both routine (ambient

environment) and non-routine (non-ambient temperature and relative humidity)

modes.

It is still another object of the present invention to provide an 5 environmentally controlled sample holder that can be used with an existing

sample changer of an X-ray diffractometer (XRD) and that does not require any instrument re-alignment so that users skilled in routine operation of an X-ray

diffractometer but not skilled in alignment procedures can promptly set up the instrument for a non-ambient test and then quickly return the X-ray o diffractometer (XRD) to a routine mode for subsequent users.

It is still another object of the present invention to provide an environmentally controllable sample holder for use with an X-ray diffractometer (XRD) that provides an X-ray transparent top portion formed of polyetheretherketone (PEEK) that possesses excellent transparency to X-rays

and good resistance to heat.

Some of the objects of the invention having been stated, other objects will become evident as the description proceeds, when taken in connection with

5 the drawings described below.

Brief Description of the Drawings Figure 1 is an exploded view of the sample holder element of the

o environmentally controllable sample holder of the present invention;

Figure 2 is an exploded perspective view of the housing for the sample

holder element of the environmentally controllable sample holder of the present

invention;

Figure 3 is a perspective view of the environmentally controllable

5 sample holder of the present invention mounted on a six-position X-ray

diffractometer (XRD) sample changer; and

Figure 4 is graph of the test results from X-ray powder diffraction analysis of ACYCLOVIR™ obtained during conversion using the

environmentally controllable sample holder of the present invention with a

o SCINTAG Model No. XDS2000 X-ray diffractometer.

Best Mode for Carrying Out the Invention X-ray diffraction at ambient and non-ambient conditions is a key tool in

5 elucidating the physical behavior of drugs. Different crystal forms or "polymorphs" of a drug substance may vary in their chemical and physical stability. Issues such as which crystal form is the most stable at a given temperature and humidity, conversion routes from one form to another with

changing environmental conditions, or loss or gain of moisture with varying

temperature and relative humidity, must be resolved before a pharmaceutical company can submit a drug application (e.g., NDA) to regulatory authorities.

Applicants have developed a device to improve the overall speed with which

one can elucidate the crystalline properties of drug substances, both in their

pure form and in a drug product matrix, at non-ambient laboratory conditions.

As is well known to those skilled in the art, commercial environmental sample holders of X-ray diffractometers such as the SCINTAG Model No. XDS2000 normally require removal of the sample changer and installation and

alignment of the environmental sample holder. This procedure requires

considerable time and effort from a highly skilled user of an X-ray diffractometer

(XRD), particularly installation and alignment of the environmentally controlled sample holder. Applicants have developed an improved environmentally controlled sample holder that fits directly onto the sample changer of an X-ray diffractometer without any re-alignment requirement. Applicants' novel

environmentally controlled sample holder provides a significant advancement in convenient operation of an X-ray diffractometer with multiple users in both routine (ambient environment) and non-routine (non-ambient temperature and relative humidity) modes and thus requires less skilled X-ray diffractometer technicians to effect placement and removal of the novel sample holder from the sample changer of an XRD. Simply stated, applicants' novel environmentally controlled sample holder can be used by technicians not skilled in X-ray diffractometer instrument

alignment and thereby allows for quick conversion between normal and environmentally controlled X-ray diffractometer analysis runs. Applicants' environmentally controlled sample holder is not intended to replace

conventional commercial environmentally controlled sample holders presently

available for use with XRD devices, such as the SCINTAG Model No. XDS2000

described herein. However, applicants' sample holder does provide for

convenience and ease of use in applications such as pharmaceutical development laboratories and the like by multiple X-ray diffractometer users of varying skill levels.

Although the preferred embodiment of applicants' environmentally controllable sample holder described herein was designed for use with the

SCINTAG Model No. XDS2000 powder diffractometer, applicants believe that

the invention is readily adaptable to other SCINTAG diffractometers and may

also be used with other brands and models of X-ray diffractometers with minor modifications thereto. Thus, applicants believe that their invention is not limited to use only with the SCINTAG Model No. XDS2000 X-ray diffractometer, but that it may be used with a variety of different brands and models of X-ray diffractometers.

Referring now to Figure 1-3, applicants' environmentally controllable sample holder element is generally designated 10. Sample holder element 10 comprises base 12, preferably formed of ceramic, and consisting of a stem and flat disk mounted thereon. A heating element 14, most suitably a mica heater

Catalog No. HM6807R2.0L12T1 available from Menko Products, Inc., is used

to heat a powder test sample. Heating element 14 comprises a mica disk having resistive wires (not shown) mounted thereto. Insulation disk 16,

preferably formed of ceramic material, is positioned beneath heating element

14 and heat sink disk 18 positioned on heating element 14. Heat sink disk 18

is most suitably formed of steel and includes a temperature sensor TS embedded therein to provide a feedback signal for use in controlling heating

element 14. An O-ring 20 is provided and sized so as to seat around the circumference of heat sink disk 18. O-ring 20 serves to provide a sealing

engagement when sample holder element 10 is inserted into aperture A in the

bottom of housing 40 (see Figure 2) to be described hereinafter that is removably placed over sample holder element 10 once sample holder element

10 is installed on the sample changer (see Figure 3) of X-ray diffractometer

XRD. A screw 22 serves to secure together ceramic base 12, insulation disk

16, heating element 14 and steel heat sink disk 18 (having the embedded temperature sensor TS therein). A sample plate disk 24, preferably formed from a single crystal (511) or (510) silicon wafer, serves as a platform for a powder sample (not shown) to be analyzed.

Housing 40, preferably formed of steel, is shown in Figure 2 and is adapted to cover and seal sample holder element 10 once the sample holder element is attached to the sample changer of X-ray diffractometer XRD. Housing 40 is provided with air inlet nozzle 42A and air exhaust nozzle 42B to provide for the introduction of gases (either inert-nitrogen-atmosphere or varying relative humidity gases) into housing 40 to provide a predetermined

environmentally controlled analysis of a powder sample. A thermocouple 44 is provided in the housing and extends into the internal space in order to

measure the temperature of the air in housing 40. The temperature measured

by thermocouple 44 may, optionally, also be used in addition to the signal from temperature sensor TS to control heating element 14. Finally, housing 40 is provided with an arcuate top cover 46 formed from polyetheretherketone

(PEEK) in order to provide high X-ray transparency (about 75%) and resistance to heat.

As shown in Figures 1-3, ceramic base 12, insulation disk 16, heating element 14, heat sink disk 18 (including temperature sensor TS embedded

therein) and surrounding O-ring 20 would normally be pre-assembled. Base

12 sits flush with the X-ray diffractometer sample changer and is easily

attachable and removable therefrom. A selected powder sample is loaded onto sample plate disk 24. The silicon does not produce any significant interference for radiation.

Once the powder sample is loaded onto sample plate disk 24, sample holder element 10 is then covered with steel housing 40 shown in Figure 2. Air

inlet nozzle 42A and air exhaust nozzle 42B allow for the introduction of gases into housing 40, either inert-nitrogen-atmosphere or varying relative humidity (0 to 100%). Thermocouple 44 is inserted into housing 40 in order to measure the temperature of the air in housing 40 surrounding the powder sample on sample plate disk 24. Temperature sensor TS embedded in heat sink disk 18

will provide feedback to control heating element 14. The assembled, loaded

environmentally controllable sample holder consisting of sample holder element 10 and housing 40 may then be installed on sample changer SC of X-ray diffractometer XRD (see Figure 3) and sample data acquired.

Referring again to Figure 3, applicants' environmentally controllable

sample holder consisting of sample holder element 10 shown in Figure 1 and

housing 40 shown in Figure 2 positioned thereover is shown mounted to sample changer SC of X-ray diffractometer XRD. A conventional sample holder SH is shown in the next adjacent position of the six-position sample

changer SC of X-ray diffractometer XRD.

The vertical position of the powder sample with respect to the incident

X-ray beam is critical to assure accurate diffraction data. Due to the thickness of ceramic insulating disk 16, the powder sample positioned within environmental sample changer SC of X-ray diffractometer XRD is 22.5 mm above the rotary platform. This height is in excess of the sample position of 9.6

mm in the standard front packed stainless steel sample holders used with the

SCINTAG Model No. XDS2000 diffractometer described herein. In order to prevent the necessity of re-alignment between uses of applicants' environmentally controllable sample holder consisting of sample holder element

10 and housing 40, special taller stainless steel conventional sample holders

SH (see Figure 3) can be used in addition to applicants' environmentally controllable sample holder with the six-position sample changer SC of the SCINTAG XRD.

Applicants' novel environmentally controllable sample holder for use

with the sample changer of an X-ray diffractometer (e.g., the SCINTAG XDS2000 diffractometer) offers a number of advantages over conventional commercially available environmentally controlled sample holders or sample

stages. The advantages of applicants' invention include the following:

1. Applicants' environmentally controllable sample holder can be run

in the automatic mode without any system re-alignment to the X-ray diffractometer.

2. The polyetheretherketone (PEEK) top portion 46 of housing 40 allows for optimum diffracted intensity.

3. Gas inlet nozzle 42A allows for the introduction of gases of desired specific composition and moisture content.

4. O-ring 20 allows for sample holder element 10 to exclude

external air while allowing easy outer sample access and cleaning.

5. Temperature measurement of both the powder sample and the

surrounding atmosphere can be easily effected.

6. The insulated design of applicants' environmentally controllable sample holder prevents damage to sample changer SC of X-ray diffractometer XRD. 7. Applicants' environmentally controllable sample holder is

compact, easily removable, and inexpensive due to lightweight ceramic and stainless steel construction.

An experimental test using applicants' environmentally controllable sample holder is described below.

I. Experimental Testing A. Reagents

Glaxo Wellcome ACYCLOVIR™ (>99% pure) was used. Stearic acid

was obtained from Mallinckrodt, urea was obtained from Sigma, and tin was purchased from Thermal Sciences.

B. X-ray Powder Diffraction

X-ray powder diffraction analyses were completed on a SCINTAG

XDS2000 X-ray powder diffractometer (XRD) equipped with a PELTIER cooled

solid state detector. The operating conditions incorporated: CuKα radiation (45

kV/40 mA), θ/θ geometry, 1-mm divergent slit, 2-mm incident scatter slit, 0.5-

mm diffracted beam scatter slit, 0.3-mm receiving slit, and 0.03-deg two-theta computer (A/D) resolution. Soller slits were incorporated in the incident and diffracted X-ray beams. The diffractometer was operated in the 250-mm goniometer radius and continuous scanning mode at 10° 2-theta/minute for all

environmental work. C. Humidity Control

Relative humidity in the environmental chamber was controlled by a

humidity generator (RH-100 from VTI Corp. of Hialeah, Florida). Typical operating parameters for the humidity generator included a humidifier set temperature of 40°C and a gas flow rate of 400 cc/minute to the environmental

chamber.

The VTI RH-100 humidity generator is capable of producing an output

gas stream ranging from less than 5% to greater than 95% relative humidity at

25°. Typical flow rate settings of the output gas range from 400 to 1500

cc/minute. Relative humidity control at temperatures slightly above ambient

(30-40°C) may be achieved by increasing the temperature of the humidifier and

heating the gas transfer line between the VTI RH-100 and the environmental

chamber.

D. Differential Scanning Calorimetry (DSC)

DSC scans of stearic acid, urea, and tin were obtained on a THERMAL ANALYST TA4200 thermal analyzer using a DSC 2920 module. Nitrogen purge was set at 40 mL/min. Samples were sealed in aluminum pans with a pinhole punched into the lids.

II. Experimental Results A. Temperature Accuracy To evaluate applicants' environmentally controllable sample chamber for

accuracy in temperature, hotstage XRD was performed on samples of stearic acid, urea, and tin to determine the onset of melting; the XRD results are

compared to that obtained from DSC as shown below in Table 1.

TABLE 1

B. X-ray Diffraction Results for ACYCLOVIR™

X-ray diffraction analysis was performed on ACYCLOVIR™, a

compound which is known to undergo polymorphic phase transitions under different temperature and relative humidity conditions. ACYCLOVIR™ exists

in a hydrated form (Form A) and two anhydrate forms (Forms B and C). The

initial form of ACYCLOVIR™ in this study is Form A (3/5 hydrate). The sample

was loaded into the sample holder as described above. Referring to Figure 4, when Form A was heated to 120°C, this hydrated

form lost its lattice water and converted to Form B, as indicated by the appearance of peaks at 2Θ angle of 8.2° and 14.8°. Form B converted back to

Form A after subsequent exposure to 80% RH controlled with the VTI RH-100 humidity generator at 25°C. When Form B was further heated to 160°C, it converted to Form C which exhibited distinctive peaks at 2Θ angle of 8.4° and

13.9°. When Form C was exposed to 95% RH, the peaks of Form A were

observed, indicating that moisture was rapidly absorbed as Form C converted to the hydrated Form A (see Figure 4).

Summarily, most X-ray diffractometer (XRD) manufacturers (e.g.,

Scintag, Inc.) provide environmentally-controlled sample holders (sample stages) for obtaining X-ray diffractograms under non-ambient conditions (e.g.,

elevated and sub-ambient temperatures). However, the use of such devices

normally requires time consuming removal of the sample changer, followed by

installation and alignment of the environmentally controlled sample stage or sample holder. Then, in order to return to a routine operation mode, removal of the environmentally controlled stage or holder is required and re-installation

and re-alignment of the sample changer necessitated. Such instrumental

manipulation of the XRD and environmentally controlled sample stage or holder

does not provide any problem for dedicated and skilled XRD technicians, but

it does provide difficulties to multiple XRD users of varying skill level. Thus, applicants' novel environmentally controllable sample holder can be used by those not skilled in XRD instrument alignment in order to allow for quick

conversion between normal and environmentally controlled XRD analysis runs. It will be understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation-the invention being defined by the claims.

Claims

CLAIMSWhat is claimed is:

1. A controllable sample holder for use with an X-ray diffractometer

(XRD), comprising: (a) a sample holder comprising a sample plate, a base adapted for removable attachment to the XRD, a heating element positioned

between said base and said sample plate, and temperature

sensing means adapted to provide a feedback signal for use in controlling the temperature of said heating element; and (b) a housing for sealingly enclosing said sample holder comprising

air inlet and air exit nozzles for introducing and exhausting gases from said housing, and an X-ray transparent portion.

2. The apparatus of claim 1 , wherein said sample plate is a disk

made of silicon.

3. The apparatus of claim 1 , wherein said base of said sample

holder is made of ceramic and comprises a disk with a stem depending

therefrom.

4. The apparatus of claim 1 , wherein said heating element comprises a mica disk having resistive wires mounted thereto and further comprises an insulation disk beneath said mica disk and a heat sink disk with an O-ring fitted therearound above said mica disk.

5. The apparatus of claim 4, wherein said temperature sensing means are embedded in said heat sink disk.

6. The apparatus of claim 1 , wherein said housing has an aperture

in the bottom thereof for sealingly receiving said sample holder therein.

7. The apparatus of claim 1 , wherein said housing has a temperature sensing means mounted therein so as to measure the temperature

therein.

8. The apparatus of claim 1 , wherein the X-ray transparent portion

of said housing is made of polyetheretherketone (PEEK).

9. The apparatus of claim 8, wherein the base of said housing is made of steel.

10. The apparatus of claim 1 , wherein said XRD includes a sample

changer and said sample holder is adapted for use with the sample changer of

the X-ray diffractometer (XRD).

11. An environmentally controllable sample holder for use with the

sample changer of an X-ray diffractometer (XRD), comprising: (a) a sample holder comprising a silicon sample plate, a ceramic

base adapted for removable attachment to the XRD sample

changer, a heating element positioned between said base and said sample plate, and a temperature sensor adapted to provide

a feedback signal for use in controlling the temperature of said heating element; and

(b) a housing for sealingly enclosing said sample holder, said housing having an aperture in the bottom thereof for sealingly receiving said sample holder therein, air inlet and air exit nozzles for introducing and exhausting gases from said housing, a

thermocouple mounted in said housing so as to measure the

temperature therein, and an X-ray transparent polyetheretherketone (PEEK) top portion.

12. The apparatus of claim 11 , wherein said base of said sample

holder comprises a disk with a stem depending therefrom.

13. The apparatus of claim 11 , wherein said heating element is a

mica disk having resistive wires mounted thereto and further comprises an

insulation disk beneath said mica disk and a heat sink disk with an O-ring fitted therearound above said mica disk.

14. The apparatus of claim 13, wherein said temperature sensor is embedded in said heat sink disk.

15. The apparatus of claim 11 , wherein the base of said housing is

made of steel.

16. In combination (1) an X-ray diffractometer (XRD); and (2) an environmentally controllable sample holder for use with said XRD, said sample holder comprising:

(a) a sample holder comprising a sample plate, a base adapted for removable attachment to the XRD, a heating element positioned o between said base and said sample plate, and a first temperature sensor adapted to provide a feedback signal for use in controlling the temperature of said heating element; and (b) a housing for sealingly enclosing said sample holder, said

housing having an aperture in the bottom thereof for sealingly receiving said sample holder therein, air inlet and air exit nozzles

for introducing and exhausting gases from said housing, a

second temperature sensor mounted in said housing so as to measure the temperature therein, and an X-ray transparent top portion.

17. The combination of claim 16, wherein said XRD includes a

sample changer and said sample holder is adapted for use with the sample changer of the XRD.

18. The combination of claim 17, wherein said XRD has a six-position sample changer.

19. The combination of claim 17, wherein said XRD has a twelve- position sample changer.

20. The combination of claim 16, wherein said sample plate is a disk made of silicon.

21. The combination of claim 16, wherein said base of said sample

holder is made of ceramic and comprises a disk with a stem depending therefrom.

22. The combination of claim 16, wherein said heating element is a mica disk having resistive wires mounted thereto and further comprises an insulation disk beneath said mica disk and a heat sink disk with an O-ring fitted therearound above said mica disk.

23. The combination of claim 22, wherein said first temperature

sensor is embedded in said heat sink disk.

24. The combination of claim 16, wherein the X-ray transparent top portion of said housing is made of polyetheretherketone (PEEK).

25. A method of analyzing a sample with a controllable sample holder for use with an X-ray diffractometer (XRD), comprising the steps of:

(a) providing a controllable sample holder for use with an X-ray

diffractometer (XRD), said controllable sample holder comprising: (i) a sample holder comprising a sample plate, a base adapted for removable attachment to the XRD, a heating

element positioned between said base and said sample

plate, and temperature sensing means adapted to provide a feedback signal for use in controlling the temperature of

said heating element; and

(ii) a housing for sealingly enclosing said sample holder comprising air inlet and air exit nozzles for introducing and

exhausting gases from said housing, and an X-ray transparent portion; and

(b) analyzing a selected sample positioned in the controllable sample o holder subsequent to placement of the controllable sample holder

onto said X-ray diffractometer (XRD).

26. A process of analyzing a sample with a controllable sample holder for use with an X-ray diffractometer (XRD), comprising the steps of: (a) utilizing in combination (1 ) an X-ray diffractometer (XRD); and (2)

an environmentally controllable sample holder for use with said XRD, said sample holder comprising:

(i) a sample holder comprising a sample plate, a base

adapted for removable attachment to the XRD, a heating

element positioned between said base and said sample

plate, and a first temperature sensor adapted to provide a feedback signal for use in controlling the temperature of

said heating element; and

(ii) a housing for sealingly enclosing said sample holder, said

housing having an aperture in the bottom thereof for sealingly receiving said sample holder therein, air inlet and air exit nozzles for introducing and exhausting gases

from said housing, a second temperature sensor mounted

in said housing so as to measure the temperature therein,

and an X-ray transparent top portion; and (b) analyzing a selected sample positioned in the environmentally

controllable sample holder subsequent to placement of the controllable sample holder onto said X-ray diffractometer (XRD).