Ammonia and polyamine detection method using ion mobility spectrometry

Abstract

The present invention relates to methods of analyte detection, ion mobility spectrometers (IMS) (10) suitable for point-of-use, including novel heater assemblies (600), and consumables (100; 400) including reagents (130) and a vial (410) and stopper (420) assembly. The reagent is an alkali metal bicarbonate solution which, when heated, changes pH such that it can react with a sample (120) to generate amines and polyamines which are driven off as a gas (126) and ionized (127) such that they can be detected.

Description

[0001] This invention relates to an analyte detection method and an ion mobility spectrometer (IMS) suitable for point-of-use, comprising a novel heater assembly and consumables including reagents and vials and stopper assemblies. Background Technology

[0002] Ion mobility spectrometry (IMS) has a history of over 100 years. It is an analytical method based on the separation of gaseous molecules from their induced charges by mass and charge (Verbeck et al., 2002; Creaser et al., 2004; Kanu et al., 2008; Westhoff et al., 2009; Dodds and Baker, 2019). It is a highly sensitive analyte detection method (ng / L to pg / L) that does not require pre-concentration or labeling of the analyte before analysis (Westhoff et al., 2009).

[0003] It has the advantages of being fast and having extremely low limits of detection and quantitation.

[0004] IMS has been used as an in vitro diagnostic device to detect bacterial infections and viruses (Blankenstein). wait , 2015; DeMuri and Wald, 2014; Slots and Slots, 2011; Corstjens, Paul LAM wait (2016) and cancer (Westhoff) wait , 2009; Gugliucci, 2004; Miller-Fleming wait (2015).

[0005] Saliva has been used as a specimen for testing patients with HIV, HPV, and hepatitis C (Corstjens, Paul L.A.M.) wait (2016).

[0006] However, a key problem with using IMS as an on-the-fly device to detect amines and polyamines is the extreme corrosivity of the reagent (3.75M potassium hydroxide) used to raise the pH above the maximum pKa of polyamines (European Parliament and Council of the European Union, 2008b, 2008a).

[0007] This problem is overcome by using reagents that are not extremely corrosive during treatment but can achieve pH values ​​above the maximum pKa of polyamines (with pH values ​​below 11.5) when subsequently heated in a modified IMS (for immediate use), making them non-ionizable and unaffected by hydrogen bonding in polar solvents. This means they have lower volatilization energy requirements and volatilize at appropriate temperatures above their pKa.

[0008] CN106198702 teaches the use of IMS to detect controlled drugs such as heroin, ketamine, and cocaine in saliva samples. It does not study polyamines and uses sodium carbonate or sodium bicarbonate to adjust the pH to between 8.5 and 9.5, while using "solvents"—methanol, ethanol, or acetonitrile—to improve sensitivity.

[0009] The problem with using sodium carbonate or sodium bicarbonate is that the pH value is lower than the pKa of many amines / polyamines that the applicant seeks to detect when identifying, for example, a specific virus, bacteria, or cancer in a sample, where a pH value higher than 9.5 is desired, and more preferably higher than 10, because many amines to be detected have pKa values ​​above pH 9.5, as illustrated in Tables 1 and 2 below, which illustrate the pKa of amino acids (Table 1) and the pKa of a range of primary amines, secondary amines, tertiary amines, aryl amines, and heterocyclic amines (Table 2).

[0010] Table 1

[0011]

[0012] From Lehninger's Principle of Biochemistry.

[0013] Table 2

[0014] List of pKb values ​​of different amines

[0015]

[0016] Table 2 is from - https: / / i.pinimg.com / 736x / d0 / 9a / 34 / d09a34ad182940bbdc878f1fc973da91.jpg Summary of the Invention

[0017] According to a first aspect of the present invention, an immediate method for analyte detection using ion mobility spectrometry is provided, the method comprising the following steps:

[0018] i) Obtaining samples from patients;

[0019] ii) Place the sample and reagents together in an ion mobility spectrometer.

[0020] Its features

[0021] iii) The reagent is a solution having a pH value below 11.5 at room temperature, which dissociates upon heating to up to 110°C to raise the pH value above the pKa value of one or more target amines and polyamines present in the sample, and

[0022] iv) Heating the reagents and sample, and vaporizing and ionizing the one or more target amines and / or polyamines to form gaseous analytes, which pass through the drift region of the IMS to reach the Faraday plate, where they are detected.

[0023] The characteristic feature is that the reagent is one of potassium bicarbonate solution, rubidium bicarbonate solution or cesium bicarbonate solution.

[0024] In one implementation, the instantaneous analyte detection method further includes the following steps:

[0025] v) Compare the characteristic spectrum detected at the Faraday plate with the known characteristic spectrum indicating the disease, and make a diagnosis based on the comparison.

[0026] Preferably, the reagent is a bicarbonate solution.

[0027] Preferably, the bicarbonate exists in the form of an alkali metal salt.

[0028] Preferably, the alkali metal salt is a cesium salt, potassium salt, rubidium salt, or sodium salt, with cesium bicarbonate being the most preferred.

[0029] Preferably, the sample and reagent are heated to between 80-110°C.

[0030] According to a second aspect of the invention, a consumable or a component kit containing a consumable is provided for use with an instantaneous ion mobility spectrometer (IMS) analyte detection device, the consumable comprising a reagent, the reagent being a bicarbonate solution selected from potassium bicarbonate solution, cesium bicarbonate solution or rubidium bicarbonate solution.

[0031] Preferably, the concentration of the reagent is greater than 2.5M.

[0032] In one embodiment, the reagent is contained in a container that includes a dropper for applying the reagent to a sample.

[0033] The container can be a squeeze bottle with a dropper or a bottle with a separate pipette dropper.

[0034] According to a third aspect of the invention, a consumable comprising a vial and a stopper, or a component kit comprising a consumable, is provided, wherein the vial has an open end away from the closed end of the vial and includes at least two slots or through holes through which gaseous analytes generated by the reagent acting on the sample escape when the vial, sample, and reagent are heated in situ in an IMS using the stopper.

[0035] In one embodiment, the notch creates an expandable, resilient wall such that when inserted into the open end, the stopper locks onto the vial.

[0036] Preferably, the vial further includes a shoulder located directly below the at least two slots for positioning the vial within the heating chamber of the heater assembly of the IMS.

[0037] Preferably, the stopper includes a shoulder to limit the extent to which the stopper is inserted into the open end, such that the lower region of the notch remains open, thereby allowing the vaporized analyte to enter the ionization zone therein when heated in the IMS.

[0038] In one embodiment, the stopper has a rod extending from a lower end, with a swab provided at the end of the rod away from the end attached to the stopper.

[0039] This arrangement is very useful for things like saliva swabs.

[0040] Of course, if the sample is collected as a liquid sample (such as urine, sputum, or blood) or a tissue sample (from, for example, a biopsy), the sample can be placed in a vial without a swab.

[0041] According to a fourth aspect of the present invention, an instantaneous ion mobility spectrometry (IMS) analyte detection apparatus is provided for use with the method of the first aspect or the consumables of the second or third aspect, comprising:

[0042] i) Ionization region; and

[0043] ii) Drift zone;

[0044] The ionization region includes

[0045] a) A heating assembly, the heating assembly including a sample receiving cavity;

[0046] b) Gas outlet; and

[0047] c) Ionization source

[0048] The drift region includes

[0049] d) Ion shutter;

[0050] e) Drift ring;

[0051] f) Aperture grid; and

[0052] g) Faraday board;

[0053] Its features

[0054] iii) The sample receiving cavity is shaped to retain a vial containing the sample and reagents, the vial being sealed with a stopper and containing a through-hole that allows gas to be released into the ionization region;

[0055] iv) The heater is shaped to provide a cavity for heating vials containing samples and reagents; and

[0056] v) A management system for controlling the heater.

[0057] The management system ensures that the heater heats to the required temperature and duration, causing the amines and / or polyamines in the sample to be expelled as gases and ionized in the ionization region to form charged analytes, which travel through the drift region of the IMS to the Faraday plate, where they are detected. Attached Figure Description

[0058] Embodiments of the invention are further described below with reference to the accompanying drawings, wherein:

[0059] Figure 1 This is a schematic diagram showing the main components and principles of ion mobility spectrometry (IMS);

[0060] Figures 2a and 2b are schematic diagrams illustrating an embodiment of the first consumable (reagent) of the present invention;

[0061] Figures 3a, 3b and 3c are schematic diagrams illustrating the second consumable of the present invention (bottle and stopper - optionally with a swab connected via a rod);

[0062] Figure 4a is an exploded view of the heating assembly of the present invention for use as an IMS as a point-of-care analyte detection device;

[0063] Figure 4b is a cross-sectional view of the heating assembly of Figure 4a together with the vial and stopper shown in Figures 3a and 3b (as in one embodiment, the rod and swab are attached to the stopper), wherein the vial and stopper are located in the assembly;

[0064] Figure 5 It is a graph showing the temperature increase versus time;

[0065] Figure 6 It is a curve of pH versus temperature for the control and potassium hydroxide solution;

[0066] Figure 7 It is a graph of pH versus temperature for sodium carbonate (outside the scope of this invention);

[0067] Figure 8 It is a graph of pH versus temperature for potassium carbonate (outside the scope of this invention);

[0068] Figure 9 It is a graph of pH versus temperature for rubidium carbonate (outside the scope of this invention);

[0069] Figure 10 It is a graph of pH versus temperature for cesium carbonate (outside the scope of this invention);

[0070] Figure 11It is a graph of pH versus temperature for 1.06M sodium bicarbonate (outside the scope of this invention);

[0071] Figure 12 It is a curve of pH versus temperature for 2M potassium bicarbonate;

[0072] Figure 13 This is a pH versus temperature curve for 2M potassium bicarbonate (pH adjusted);

[0073] Figure 14 It is a curve of pH versus temperature for cesium bicarbonate;

[0074] Figure 15 It is a graph of pH versus temperature for 3.75M cesium bicarbonate;

[0075] Figure 16 This is a graph showing pH versus temperature for 4.33M rubidium bicarbonate; and

[0076] Figure 17 This is a bar graph showing the results of the different compounds tested. Detailed Implementation

[0077] Reference Figure 1 IMS (10) contains two regions - ionization region (20) and drift region (30).

[0078] The ionization region includes a sample receiving cavity (not shown), an ionization source (22), and a gas outlet (24) through which unionized molecules (26) exit.

[0079] The drift region includes an ion shutter (32), a drift ring (34), a aperture grid (36), and a Faraday plate (38).

[0080] The IMS of the present invention is adapted for point-of-care analyte detection by including a heater assembly (600) (which includes a ring heater (640)) (see Figures 4a and 4b and Figures 2a, 2b, 3a, 3b and 3c), the assembly being shaped to hold a vial (410) containing a sample (120) and a reagent (130), which is sealed with a stopper (420) and includes one or more through holes (A), preferably formed by a notch (460), allowing the release of gaseous analytes (126) generated when the sample (120) and the reagent (130) are heated, the reagents causing amines / polyamines present in the sample to volatilize (126), so that they enter the ionization zone (20) and are ionized (127) into charged analytes (128).

[0081] In use, the ion shutter (32) blocks non-ionized molecules (26) from entering the drift region (30), while the drift gas (31) carries these molecules away through the gas outlet (24).

[0082] The ionized analyte (128) flows in the opposite direction to the electric field (40) and opposes the drift gas (31), which acts as a barrier to the migration of the charged analyte (128) in the electric field and reduces the length of the drift region required to achieve molecular separation. The drift ring (34) maintains the electric field on the column.

[0083] As charged analytes (128) move along the electric field-resistant drift gas (31) flow, they reach a pore gate (36), which acts as a gated barrier for all ions to ensure accurate drift calculations toward the Faraday plate. When the analyte contacts its surface, the Faraday plate (38) detects the charge of the analyte, and this time from introduction to detection is recorded.

[0084] Once the charged analyte (128) comes into contact with the Faraday plate (38), its charge dissipates and it is registered on the detector. Since it can only attract ionized molecules, the molecules are no longer affected by the attraction of the electric field. It remains a gas due to the temperature of the drift region.

[0085] The reagent (130) for volatilizing amines according to the present invention was determined by the following experiments, which identified the preferred bicarbonate:

[0086] Materials and methods

[0087] Note that heating a bicarbonate solution will displace carbon dioxide and form carbonate anions, as shown in Table 3.

[0088] Table 3

[0089]

[0090] When the temperature reaches 100°C, the change in pKa of the bicarbonate-to-carbonate buffer system is calculated to be a decrease of -0.72 for a temperature change of 80°C (Benyon and Easterby, 1996). This means that the pH will be expected to buffer at around pH 9.61.

[0091] The alkali metal carbonates and bicarbonates used in this study are listed in Table 4.

[0092] Table 4

[0093] Table 4. Molecular weight, CAS number, supplier, catalog number and batch number of alkali metal bicarbonates and carbonates.

[0094]

[0095] Materials were weighed using a Bonvoisin #5002 S / N HZ5003B three-digit balance. pH was measured using a Hanna Instruments Edge HI 2020 S / N C1021024 software v1.18. The electrode was a Hanna Instruments HI 11310 S / N 533505, firmware 1.06. This electrode has an integrated temperature sensor. pH was measured at 30-second intervals using the recording function on the Edge.

[0096] The solution was weighed into a universal glass vial containing a magnetic stir bar. The sample was then placed on a preheated magnetic stirring hot plate SH-2, stirred at the lowest setting, and heated at the highest setting. As the temperature increased, the pH was measured as a measure of the displaced carbon dioxide.

[0097] The data was downloaded from Edge to a USB drive as a .CSV file and opened in MS Excel, where a graph was generated.

[0098] result

[0099] Figure 5 The display shows the rate of temperature change of 10g volume of water set on an SH-2 hot plate agitator at the maximum heating rate. The initial hysteresis phase represents the time required for the hot plate agitator to heat up.

[0100] a) 3.75M (15%) potassium hydroxide

[0101] Figure 6 (Control) The results show that 3.75M potassium hydroxide is above the pH threshold of 11.5 for corrosive alkaline solutions (European Parliament and Council of the European Union, 2008a). Heating lowered the measured pH value to just slightly below the corrosion limit.

[0102] b) 3.5M sodium carbonate

[0103] Figure 7 The 3.5M solution is shown. 3.5M sodium carbonate has a pH value above the corrosion limit of pH 11.5 (European Parliament and Council of the European Union, 2008a). Similar to 3.75M potassium hydroxide, the pH value decreases with increasing temperature, and only drops below pH 11.5 when the temperature reaches approximately 50°C.

[0104] c) Potassium carbonate

[0105] Figure 8The results showed that the pH of 3.75M potassium carbonate was also above the corrosion limit of pH 11.5 (European Parliament and Council of the European Union, 2008a). Similar to 3.75M potassium hydroxide, the pH decreased with increasing temperature, and did not drop below pH 11.5 until the temperature reached 60°C.

[0106] d) 2M rubidium carbonate

[0107] Figure 9 The effect of heat on the pH of a 2M rubidium carbonate solution was shown.

[0108] Due to the limited availability of materials, rubidium carbonate was prepared as a 2M solution. The pH of 2M rubidium carbonate is above the corrosion limit of pH 11.5 (European Parliament and Council of the European Union, 2008a). Similar to 3.75M potassium hydroxide, the pH decreases with increasing temperature, and only drops below pH 11.5 at a temperature of 65°C.

[0109] e) 4M cesium carbonate

[0110] Figure 10 The corrosion limit of 4M cesium carbonate at pH values ​​above 11.5 was shown (European Parliament and Council of the European Union, 2008a). Even when heated above 100°C, the pH value remained above 11.5.

[0111] Cesium has the largest ionic radius among stable metals and is the most basic. Because the high salt concentration in the solution leads to an increased boiling point, the solution will not boil at 105°C.

[0112] f) 1.06M sodium bicarbonate

[0113] The concentration of sodium bicarbonate solution is close to its solubility limit. This is why its concentration is lower than that of potassium hydroxide and potassium carbonate solutions.

[0114] Figure 11 The pH value of 1.06 M sodium bicarbonate starts at about 8.0 and increases by about 1.2 pH units at about 100 °C upon heating. The change in pH value is limited by the solubility of sodium bicarbonate.

[0115] g) 2M potassium bicarbonate

[0116] The concentration of potassium bicarbonate solution is close to its solubility limit. This is why its concentration is lower than that of potassium hydroxide and potassium carbonate solutions.

[0117] Figure 12 The pH values ​​for 2M potassium bicarbonate are shown to start at approximately pH 8, similar to a 1.06M sodium bicarbonate solution. Due to the higher concentration, the pH value is approximately 0.5 pH units higher than that of a 1.06M sodium bicarbonate solution.

[0118] h) 2M potassium bicarbonate - pH adjustment

[0119] The pH of a 2M potassium bicarbonate solution is increased by adding 2M equivalents of potassium hydroxide. The behavior is the same as that of the potassium carbonate solution in c).

[0120] Figure 13 The preparation of a buffer system located on the pKa is shown by heating a pH-adjusted solution. Upon heating, it drifts to a pH close to 9.61, which is the pKa of a bicarbonate-carbonate buffer at 100 °C.

[0121] i) Cesium bicarbonate

[0122] Figure 14 The results show that cesium bicarbonate is freely soluble in water and readily soluble in 10 ml of water. This is not a volumetric determination, therefore the concentration is unknown because the dissolved salt increases the total volume in the vial.

[0123] j) 3.75M cesium bicarbonate

[0124] A quantitative solution of cesium bicarbonate was prepared at a concentration of 3.75 M.

[0125] Figure 15 The results show that a higher concentration of cesium bicarbonate in a quantitative solution produces a higher final pH value than that of a 72% w / v solution.

[0126] k)4.33M rubidium bicarbonate

[0127] A quantitative solution of rubidium bicarbonate was prepared at a concentration of 4.33 M.

[0128] Figure 16 The results showed that increasing the pH of a 4.33M rubidium bicarbonate solution was similar to that of a cesium bicarbonate solution.

[0129] l) Initial and final pH of the solution

[0130] Table 5 below shows the starting and ending pH values ​​of the reagents tested.

[0131] Table 5

[0132]

[0133] The data in Table 5 are presented graphically. Figure 17 middle.

[0134] in conclusion

[0135] A key problem with using IMS as a point-of-care device for detecting polyamines is the extreme corrosivity of the reagents used to raise the pH above the maximum acid dissociation constant pKa of the polyamine (European Parliament and Council of the European Union, 2008b, 2008a).

[0136] The relatively low solubility of sodium and, to a lesser extent, potassium salts of bicarbonate anions limits their concentration in the reagent and makes them less preferred as alternatives to 3.75 M potassium hydroxide (European Parliament and Council of the European Union, 2008b) than cesium (and rubidium) salts, which are capable of raising the pH of the sample to above the highest pKa of polyamines and amines.

[0137] The solubility limits of rubidium bicarbonate and cesium bicarbonate salts are significantly higher than those of sodium bicarbonate and potassium bicarbonate, making them preferred reagents.

[0138] Data shows that when heated to 100°C, cesium bicarbonate can reach a pH > 10.5. This is close to the pH of potassium carbonate, sodium carbonate, and potassium hydroxide when heated to 100°C. Cesium is the most basic ion among any stable element in the periodic table (Sharpe, 1986).

[0139] Cesium chloride exhibits similar toxicity to its sodium and potassium chloride salts (Melnikov and Zaoni, 2010; Johnson et al., 1975). The low toxicity, high solubility, and ability to displace carbon dioxide when heated to 100°C of cesium and rubidium bicarbonate anions make these compounds ideal for the immediate detection of amines and polyamines via IMS.

[0140] Having identified certain reagents that can overcome the problems of using highly corrosive reagents to volatilize amines and polyamines for point-of-care detection using IMS, the applicant modified the IMS device and developed a novel representation of consumables for use with the methods of the present invention.

[0141] Referring to Figures 2a and 2b, the first consumable (100) (reagent (130)) of the present invention is shown, which is one of the following solutions: sodium bicarbonate ( Figure 11 ), potassium bicarbonate ( Figure 12 and 13 ) and cesium bicarbonate ( Figure 14 and 15 ).

[0142] The reagent (130) is provided in a bottle (300) with a dropper (310) and a cap (320) (Fig. 2a) or in a separate dropper (310) comprising a pipette (312), a cap (320) and a nipple (314).

[0143] The dropper simplifies the method of the present invention because the reagent can be easily and safely added to the sample (120) in the vial (410).

[0144] Referring to Figures 3a, 3b and 3c, the second consumable (400) of the present invention (bottle (410) and stopper (420)) is shown.

[0145] The vial (410) is specifically adapted for use in another aspect of the IMS (10) of the present invention and includes an opening (440) for receiving a sample (120) and a reagent (130), which is located away from the closed end (450). At least one pair of notches (460) extend from the opening (440) and extend to the shoulder (470) to form a slightly expandable elastic wall (430). When the stopper (420) is inserted into the opening (440), a through hole (A) is formed, wherein the lower region (462) of the notch (460) is in contact with the shoulder (470), and the through hole is aligned with a through hole (A') in the intermediate housing (650) component of the heating assembly (600) of the IMS (10).

[0146] In a preferred embodiment of the second consumable (400), the sample is collected on a swab (510), which forms part of the consumable, which is connected to the lower end (422) of the stopper (420) by a suitably sized rod (500), and the swab is attached to the end (502) of the rod connected to the stopper. Of course, as shown in FIG3c, which shows the stopper (420) inserted into the vial (410), the rod and swab are not necessary.

[0147] The stopper (420) also includes a shoulder (424) located above a stepped or sloping area (426) which helps to essentially close the vial (the stopper remains in the vial opening (440)) and, most importantly, ensures that the gas (126) generated during heating can exit the vial through the through hole (A) and also exit the heating assembly.

[0148] Figures 4a and 4b (with) Figure 1 (Combined) A novel heating assembly (600) for instantaneous IMS is shown.

[0149] Figure 4a is an exploded view of the heating module assembly (600) used for the second consumable (400) as described above.

[0150] The heating module assembly (600) includes an annular cavity (642) in which vials (410) containing samples (120) and reagents (130) are uniformly heated, controlled by a management system - not shown.

[0151] The heater (640) is located in the base housing member (610) and is securely held in place by a washer (620) and a screw (630). The intermediate housing member (650) includes through holes (A') that are positioned to align with the opening (A) in the vial (410).

[0152] The cap (660) and the spring-loaded plunger (670) (with a compression spring (672)) are held in place by the plunger retainer (680) and the screw (682).

[0153] In use, the second consumable (400) is located within the through hole (690) through the lower (612) assembly and is held in place by the upper (614) assembly, which serves as a cover.

[0154] Figure 4b shows the assembly (600), in which the heater (640) and gas outlet (E) are arranged in the device together with the in-place vial (410), stopper (420), rod (500) and swab (510).

[0155] References

[0156] Benyon, RJ and Easterby, JS (1996), Properties of Commonly Used Buffers - Carbonic Acid: Buffer Solutions - Base foundation Oxford University Press, Oxford

[0157] Blankenstein, T., Lytton, S.D., Leidl, B., Atweh, ​​E., Friese, K., and Mylonas, I. (2015), “Using VGTest” TM Ion mobility spectrometry (IMS) is used for point-of-care (POC) diagnosis of bacterial vaginosis (BV) in routine outpatient gynecology clinics. Obstetrics and Gynecology Archives Volume 292, Issue 2, pp. 355-362.

[0158] Corstjens, Paul LAM, Abrams, WR, and Malaud, D. (2016), “Salivary Resin and Viral Infections” Periodontology 2000 Volume 70, Issue 1, pp. 93-110.

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[0162] Firpo, MR and Mounce, BC (2020), “Multiple functions of polyamines in viral infection” biology Molecules, Vol. 10, No. 4, p. 628. NB 2022-01 133 Gugliucci, A. (2004), “Polyamines as Clinical Laboratory Tools”, Clinical Chemistry Volume 344, Issues 1-2, pp. 23-35.

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Claims

1. A real-time method for analyte detection using ion mobility spectrometry, comprising the following steps: i) Obtain samples (120) from patients; ii) Place the sample and reagent (130) together in the ion mobility spectrometer (10), Its features iii) The reagent is a solution having a pH value below 11.5 at room temperature, which dissociates upon heating to up to 110°C to raise the pH value above the pKa value of one or more target amines and polyamines present in the sample. iv) The reagents and sample are heated, and the one or more target amines and / or polyamines are vaporized (126) and ionized (127) to form gaseous analytes (128), which pass through the drift region (30) of the IMS to reach the Faraday plate (38), where they are detected. The characteristic feature is that the reagent is one of potassium bicarbonate solution, rubidium bicarbonate solution or cesium bicarbonate solution.

2. The immediate method for analyte detection according to claim 1 further includes the following steps: v) The characteristic spectrum detected at the Faraday plate is compared with the known characteristic spectrum of the disease indication, and a diagnosis is made based on the comparison.

3. The immediate method for detecting an analyte according to claim 1 or 2, wherein the reagent is a cesium bicarbonate solution.

4. The immediate method for detecting an analyte according to claim 1 or 2, wherein the reagent is a potassium bicarbonate solution.

5. The immediate method for detecting an analyte according to claim 1 or 2, wherein the reagent is a rubidium bicarbonate solution.

6. An immediate method for detecting an analyte according to any of the preceding claims, wherein the sample and reagent are heated to 80-110°C.

7. Consumables (100) or component kits containing consumables for use with an instantaneous ion mobility spectrometer (IMS) analyte detection device (10), the consumables containing reagents, the reagents being a bicarbonate solution selected from potassium bicarbonate solution, cesium bicarbonate solution or rubidium bicarbonate solution.

8. The consumable (100) containing a reagent or the component kit containing a consumable according to claim 7, wherein the reagent is a cesium bicarbonate solution.

9. The consumable (100) containing the reagent or the component kit containing the consumable according to claim 8, wherein the reagent has a concentration of at least 2.5 M.

10. The consumable (100) containing a reagent or the component kit containing a consumable according to claim 8 or 9, wherein the reagent is contained in a container (300) comprising a dropper (310) for applying the reagent (130) to a sample (120).

11. A consumable (400) comprising a vial (410) and a stopper (420) or a component kit comprising the consumable, wherein the vial has an open end (440) away from the closed end (450) of the vial and includes at least two slots or through holes (460) through which gaseous analytes (126) generated by the reagent (130) acting on the sample (120) escape when the vial, sample and reagent are heated in situ in an IMS (10) with the stopper.

12. The consumable (400) of claim 11 or a component kit containing the consumable, wherein the notch creates an expandable resilient wall (430) such that when inserted into the open end (440), the stopper locks onto the vial.

13. The consumable (400) or component kit containing the consumable according to claim 11 or 12, wherein the vial further comprises a shoulder (470) located directly below the at least two slots (460) for positioning the vial in the heating chamber (642) of the IMS.

14. The consumable (400) or component kit comprising any one of claims 11-13, wherein the stopper (420) includes a shoulder (424) to limit the extent to which the stopper is inserted into the open end (440), such that the lower region (462) of the notch (460) remains open, thereby allowing vaporized analyte (126) to enter the ionization region (20) therein when heated in the IMS (10).

15. The consumable (400) or component kit containing the consumable according to any one of claims 11-14, wherein the stopper has a rod (500) extending from a lower end (422), and a swab (510) is provided at an end (502) of the rod away from the end attached to the stopper (420).

16. An instantaneous ion mobility spectrometry (IMS) analyte detection device (10) suitable for use with the method of any one of claims 1-6 or the consumables (100; 400) of any one of claims 7-15, comprising: i) Ionization region (20); and ii) Drift zone (30); The ionization region includes a) A heating assembly (600) comprising a sample receiving cavity (690); b) Gas outlet (24); and c) Ionization source (22) The drift region includes d) Ion shutter (32); e) Drift ring (34); f) Aperture (36); and g) Faraday plate (38); Its features iii) The sample receiving cavity (690) is shaped to hold a vial (410) containing a sample (120) and a reagent (130), the vial being sealed with a stopper (420) and having a through hole (A) to allow gas (126) to be released into the ionization region (20); iv) The heater (640) is shaped to provide a cavity (642) for heating a vial (410) containing a sample (120) and a reagent (130); and A management system for controlling the heater (640).

17. The instantaneous ion mobility spectrometry (IMS) analyte detection device (10) according to claim 16, wherein the heater (640) forms an annular cavity (642).

18. The instantaneous ion mobility spectrometry (IMS) analyte detection device (10) according to claim 16 or 17, comprising a lower (612) heating assembly that holds the vial (410) and an upper (614) heating assembly that serves as a cap.

19. The instantaneous ion mobility spectrometry (IMS) analyte detection apparatus according to claim 16, wherein the management system manages the temperature of the heater (640) such that amines and / or polyamines in the sample (120) are expelled as gases (126) and ionized (127) in the ionization region (20) to form charged analytes (128), which pass through the drift region (30) of the IMS (10) to reach the Faraday plate (38), where they are detected.

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