GB2388659A

GB2388659A - Method of preparing a working solution

Info

Publication number: GB2388659A
Application number: GB0319575A
Authority: GB
Inventors: Stephen John Haswell; Gillian Mary Greenway; Thomas Mccreedy
Original assignee: Micro Chemical Systems Ltd
Current assignee: Micro Chemical Systems Ltd
Priority date: 1999-06-21
Filing date: 1999-06-21
Publication date: 2003-11-19
Anticipated expiration: 2019-06-21
Also published as: GB0319575D0; GB0319576D0; GB2387655B; GB2388659B; GB2387655A

Abstract

A method of preparing a working solution of a substance at a desired concentration in a chemical device comprises providing a substance in a soluble form in a chemical device and contacting the substance with a solvent for the substance in the device. Contact between the substance and the solvent is controlled so as to produce a working solution of the substance in the solvent at a concentration dependent on said control. The substance is a porous solid.

Description

F.THOn OF PREPARING A WOWING SQLUTTON The invention relates to a method of

preparing a working solution of a substance at a desired concentration in a chemical device.

The term "chemical devices" is used in this specification to include devices used for

performing chemical reactions (including biochemical reactions) and/or for performing analysis and separation of chemical (including biochemical) substances.

Such analysis and separation of chemical substances may or may not include I O performing chemical reactions.

A known type of chemical device is a chip-type chemical device. A chiptype chemical device is formed from a first member (usually a plate of glass, metal, polymer, silicon or quartz) that has a surface portion and at least one groove (more 15 usually a plurality of interconnected grooves) located at the surface portion, and a second member (usually a block formed of glass, metal, polymer, silicon or quartz) having a cooperating surface portion. The surface portions are connected together such that the groove (or the plurality of interconnected grooves) is closed to form a channel (or a plurality of interconnected channels). Reagents and other chemical 20 substances may be passed through the channel (or the plurality of interconnected

channels) in a controlled manner so as to perform chemical reactions, or analysis or separation of chemical substances.

For most purposes, the current preferred method of connecting the surface portions 5 of glass members is by heating the members to a temperature close to their upper annealing temperature while the surface portions are contacting one another. This results in direct thermal connection (also called thermal bonding or annealing) of the surface portions - that is to say direct thermally induced bonding together of the surface portions without any intervening link or extraneous adhesive.

In accordance with a first aspect of the invention, there is provided a method of preparing a working solution of a substance at a desired concentration in a chemical device comprising, providing a substance in a soluble form in a chemical device, contacting the substance with a solvent for the substance in the device, and controlling 15 said contact between the substance and the solvent so as to produce a working solution of the substance in the solvent at a concentration dependent on said control, and wherein the substance is a porous solid.

The ability to prepare working solutions of a desired concentration in this way may 20 be useful when it is not practicable to introduce externally prepared working solutions into the chemical device. This may be of utility in applications such as environmental

monitoring, where chemical devices are required to perform monitoring operations repeatedly over some length of time without external maintenance.

The following is a more detailed description of embodiments of the invention, by way

5 of example, reference being made to the appended schematic drawings in which: Figure 1 shows a first stage in the manufacture of a chip-type chemical device (which is not specifically the subject of this invention); 10 Figure 2 shows a second stage in the manufacture of the device; Figure 3 is a cross-sectional view (not to scale) of the completed device; and Figure 4 is a cross-sectional view of a second chip-type chemical device (which is also 15 not specifically the subject of this invention).

The current invention relates to Method 3 set out below. Methods 1 and 2 are not specifically the subject of the current invention but these methods describe the manufacture of chemical devices of a type in which the current invention may be 20 performed.

( Methn2erLnEmanllfachring a cbip-type chemical device Referring to Figure 1, the chip-type chemical device is formed from a plate 10 of borosilicate glass having a smooth, upper, planar surface 12 and a block 14 of borosilicate glass having a smooth, lower, planar surface 16.

First and second grooves 18,20 are formed in the planar surface 12 of the plate 10.

The grooves 18,20 are formed by coating the planar surface 12 with chromium and photoresist, and then using photolithography and wet etching. The process is described in the journal Analyst, January 1997, 1 22(1R1OR).

The first groove 18 has first and second ends 22,24. The first end 22 of the first groove 18 meets the second groove 20 at a junction 26 that lies intermediate first and second ends 28,30 of the second groove 20 so that the first and second grooves together form the shape of a T. Each groove 18,20 is approximately 300 Am wide and 15 115 Elm deep.

After the fonnation of the grooves 18,20 the remaining chromium and photoresist are removed. This is done by, firstly, exposing the plate 10 to strong ultraviolet light for one to two hours before dipping the plate 10 in photoresist remover for two to three 20 hours. The plate 10 is then rinsed with water and any remaining photoresist and chromium are removed using Micro-posit Chrome Etch 1B (trade mark).

portion of the planar surface 12 of the plate 10 is then provided with a coating 34 of chromium. The coating 34 (and also the portion) extends, as a relatively narrow strip, around the T shape formed by the two grooves 18,20, as shown in Figure 2.

Hence, the coating 34 does not cover the whole of the surface 12. The coating 34 is 5 formed by first covering the whole planar surface 12, and also the inner surfaces of the grooves 18,20, with a layer of chromium. The chromium is then coated with photoresist and the photoresist and the chromium are then removed from the internal surfaces of the grooves 18,20 and the regions of the planar surface 12 where chromium is not required using standard photolithography and removal methods.

10 Finally, the remaining photoresist is removed to leave the desired chromium coating 34. As an alternative to forming the chromium coating 34 as described above, an identical chromium coating may be fonned from the chromium used during the formation of 15 the grooves 13,20. The chromium remaining after the formation of the grooves 18,20 (which covers the whole surface 12 of the plate 10 but not the surfaces of the grooves) is, instead of being totally removed as described above, removed selectively so as to leave chromium covering the portion (as described above with reference to Figure 2) of the surface 12 of the plate 10.

A micro-porous silica structure 36 is then produced so as to fill a region of the first groove 18 that extends from the first end 22 of the first groove 18 to a point near the second end 24 of the first groove 18 (see Figure 2). The silica structure 36 fills the whole volume of the groove 18 in the region and also extends slightly above the 5 groove 18 so as to fill the space lying between the portions of the coating 34 disposed at either side of the region.

The silica structure 36 is produced as follows. A solution of formamide (10% v/v), and potassium silicate (who SiO2, 9oK2O, Prolabo) is prepared at room temperature.

10 The solution is mixed for 30 seconds using a glass rod and allowed to stand for an additional two minutes. Blu-Tac (trade mark) plugs are pressed into the grooves 18,20 at either side of the region that is to receive the silica structure 36. The solution, having stood for the two minutes, is then mixed with silica bonded catalyst and introduced into the region of the first groove 18 between the Blu-Tac (trade mark) 15 plugs. The solution is added until it reaches the top of the coating 34.

The plate 10 is then heated to 100 C for one hour during which the solution solidifies to form the micro-porous silica structure 36 containing the silica supported catalyst.

The micro-porous silica structure 36 is then washed with a 2x10-2mol dm3 solution 20 of disodium tetraborate buffer in order to remove unreacted reagent.

The block 14 is then prepared by drilling first, second and third cylindrical holes 40,42,44 through the planar surface 16 and through the block 14, as shown in Figure 1. The axes of the holes 40,42,44 have the same relative spacing as the first and second ends 28,30 of the second groove 20 and the second end 24 of the first groove 5 18. The planar surface 12 of the plate 10 is then linked to the planar surface 16 of the block 14. To do this, the block 14 is placed over the plate 10 such that the planar surfaces 12,16 face one another and are separated by the chromium coating 34. The 10 axis of the first hole 40 passes through the first end 28 of the second groove 20, the axis of the second hole 42 passes through the second end 30 of the second groove 20, and the axis of third hole 44 passes through the second end 24 of the first groove 18.

The plate 10 and the block 14 are then positioned, in the orientation described above, 15 in the heating cavity of a microwave furnace (CEM Microwave Ashing System 300 [trade mark]), which is subsequently operated. The microwave furnace heats by microwave irradiation and by convective and conductive heating. However, the microwave irradiation causes the chromium coating 34 to heat more quickly than the borosilicate glass of the plate 10 and the block 14. This is because the chromium has 20 a higher tan o ratio than the borosilicate glass for the microwave frequency used (the tan o ratio = E"/E'. Where e" is dielectric loss - a measure of the efficiency with

( which absorbed microwave radiation is converted into heat, and E' iS dielectric constraint - a measure of the ability of a substance to be polarised in the electrical field

of a microwave).

5 Heating is continued until the chromium coating 34 reaches a temperature at which the chromium coating 34 bonds to the overlying portion of the planar surface 16 of the block 14. This will occur when the chromium coating 34 is near the upper annealing temperature of the borosilicate glass of the block 14. The portion of the planar surface 12 on which the coating 34 is provided and the overlying portion of the 10 planar surface 16 of the block are heated by the chromium coating 34. However, elsewhere, the plate 10 and the block 14 are at significantly lower temperatures.

Once the chromium coating 34 has bonded to the overlying portion of the planar surface 16 of the block 14 the plate 10 and the block 14 are allowed to cool slowly so 15 as to avoid cracking.

Hence, in this method, the chromium coating 34 links portions of the planar surfaces 12,16.

20 The completed chip-type chemical device is shown in Figure 3 (in which the depth of the coating 34 is exaggerated for clarity). The linking of the portions of the planar

( surfaces 12,16 by the chromium coating 34 results in the first and second grooves 18,20 being closed to form, respectively, first and second interconnecting channels (the first channel shown at 46, the second channel not shown). Each channel 46 is defined by the corresponding groove 18,20, together with adjacent regions of the S chromium coating 34 and the planar surface 16 of the block 14. Hence, the two channels 46 interconnect at the junction 26 and the second channel (corresponding to the second groove 20) has a first portion (not shown) that extends from the junction 26 to the first end 28 of the second groove 20 and a second portion (not shown) that extends from the junction 26 to the second end 30 of the second groove 20.

It will be appreciated that the silica structure 36 fills the volume of the first channel 46 at the region where it is situated.

The first, second and third holes 40,42,44 form respective reservoirs that (with the 15 exception of communicating with the channels 46) are closed at the planar surface 16 of the block 16 by the chromium coating 34. Hence, the reservoir formed by the first hole 40 communicates with the first portion of the second channel at the first end 28 of the second groove 20. The reservoir formed by the second hole 42 corrununicates with the second portion of the second channel at the second end 30 of the second 20 groove 20. The reservoir fanned by the third hole 44 communicates with the first channel 46 at the second end 24 of the first groove 18.

r Linking of the plate 10 and the block 14 as described above is advantageous over connection by conventional thermal connection. Firstly, as the linking is effected while the plate 10 and the block 14 are, for the main part, at significantly lower temperatures than those required for conventional thermal connection, the time 5 required for linking and cooling may be significantly less than that required for conventional thermal connection and cooling. Secondly, conventional thermal connection has a high failure rate - it is common for connection to be incomplete, especially in the region of the grooves 18,20. This problem may be ameliorated by linking using the chromium coating 34.

Shod 2 - method of manufacturing a chip-ty chemical device The second method is used to manufacture a second chip-type chemical device (shown in Figure 4). Components used in the second method that are common to the first and second methods are not described in detail below and, to the extent that they 15 are shown in Figure 4, are given the same reference numerals as those used above in respect of the first method.

The second chip-type chemical device is formed from a plate 10 and a block 14 identical to the plate 10 and the block 14 of the first method. First and second 20 grooves 18 (second groove not shown) are formed in the planar surface 12 of the plate

( 10, as described for the first method. The first and second grooves 18 have the same configuration as the first and second grooves 18,20 of the first method.

After the grooves 18 have been formed and the chromium and photoresist remaining 5 from their formation have been removed, as described above, a micro-porous silica structure 53 containing a silica bound catalyst is formed in a region of the first groove 18 that extends from the first end (not shown) of the first groove 18 to a point near the second end (not shown) of the first groove 18. The silica structure 53 completely fills the volume of the first groove in this region, but, unlike the silica structure of the first 10 method, does not extend above the top of the groove 18 (as there is no chromium coating 34). The silica structure 53 is formed in the same way as silica structure 36 of the first method except that the solution is added to the region of the first groove 18 up to the top of the first groove 18 (not up to the top of the chromium coating 34).

15 A portion of the planar surface 12 of the plate 10 is then provided with a coating of an organic material (not shown). The coating (and also the portion) extends, as a relatively narrow strip, around the T-shape formed by the two grooves 18 in the same manner as the chromium coating 34 of the first method. The coating is applied in a conventional manner using masks to prevent coating of the internal surfaces of the 20 grooves 18, of the microporous silica structure 53 and of the regions of the planar surface 12 where coating is not required.

The organic material of the coating is chosen so that the coating will be heated more ! quickly than the plate 10 and the block 14 by the microwave radiation used in the microwave furnace it will have a higher tan ratio than the borosilicate glass for the microwave frequency used. Additionally, the organic material should be such that S the coating vaporizes at a temperature either in the same region or slightly lower than the temperature required for conventional thermal bonding of the plate 10 and the block plate 14. Photoresist may be used to form the coating.

The block 14 is prepared as described above in the first method. The block 14 is then 10 placed over the plate 10, as described above in the first method, so that the planar surfaces 12,14 face one another and are slightly separated by the organic coating. The plate 10 and the block 14 are then placed, in this orientation, in the microwave furnace. 15 The microwave furnace is then operated. The microwave irradiation causes the organic coating to heat more quickly than the borosilicate glass of the plate 10 and the block 14. In turn, the organic coating heats the portion of the planar surface 12 on which the coating is provided and the overlying portion of the planar surface 16 of the l block 14. When these portions of the surfaces 12,16 have been heated to a 20 temperature suitable for thermal bonding of the portions, the organic coating vaporizes and the vapour escapes from between the surfaces 12,16. The vaporization

( of the organic coating brings the portions of the surfaces 12,16 into intimate contact and direct thermal connection of the portions occurs. For the most part, other than immediately adjacent the organic coating, the plate 10 and the block 14 remain at significantly lower temperatures than that required for thermal bonding.

The plate 10 and the block 14 are then cooled slowly to avoid cracking.

The chip-type chemical device formed by method 2 is shown in Figure 4. The connection of the portions of the planar surfaces 12,16 closes the first and second 10 grooves 18 so as to form, respectively, two interconnecting channels 54, (channel corresponding to second groove not shown). As indicated in Figure 4, each channel 54 is defined by the corresponding groove 18 and a region of the planar surface 16 of the block 14. The first, second and third holes 40,42,44 form reservoirs in a similar manner to that described above for the first method, but the reservoirs are closed (with 15 the exception of communicating with the channels 54) by the planar surface 12 of the plate 10.

It will be appreciated that various modifications may be made to the first and second methods. For example, whereas it is advantageous to provide the chromium coating 20 34 or the organic coating only on the portion of the planar surface 12 immediately surrounding the grooves 18, 20 as this reduces the bulk temperatures of the plate 10

and the block 14 during connection, it is not essential to do this. Alternatively, the chromium coating 34 or the orgaruc coating could be provided over the whole area of the planar surface 12 of the plate 10.

5 It is not necessary to use a coating at all. Other microwave treatable means may be used. For example, metal elements could be incorporated into the plate 10 so as to lie just below the portions of the planar surface 12 that surround the grooves 18,20.

Alternatively, metal elements could be incorporated in a similar manner into the block 14. During microwave irradiation, the metal elements would heat appropriate 10 portions of the planar surface 12 or the planar surface 16 so as to assist or effect thermal connection of the plate 10 and the block 14.

Alternatively, instead of the coatings, a microwave treatable membrane having an appropriate shape could be placed between the planar surfaces 12,16.

The microwave treatable means could also be a layer or layers of grease and dust, such as might be deposited by handling, on one or both of the planar surfaces 12,16.

Instead of being formed on the plate 10, the grooves 18,20 could be formed on the 20 surface 16 of the block 14.

The plate 10 and the block 14 need not be formed of glass, they can be made of any suitable material (e.g. metal, plastic, silicon, quartz).

Iviethor1 - method of preparing a woQ oLasubstae at Desired 5 concentration in a chemicaLdice The third method allows a solution of a substance to be prepared at a desired concentration in a chemical device. The method may be used with a chip-type chemical devices of the types manufactured using the first and second methods.

Normally, the third method will be used with chip-type chemical devices having more 10 complex arrangements of interconnecting channels than those described in the first and second methods.

porous solid substance, from which it is desired to make the working solution, is provided in a channel of a chip-type chemical device having a plurality of channels.

15 This may be done either by passing the substance through a hole in one of the members from which the device is formed or by positioning the solid substance in a groove before the members are connected together such that the connection closes the groove to form the channel containing the substance. The channel having the substance is narrow (generally having a width of SOOpm or less).

When it is desired to prepare the working solution, a solvent for the substance is passed through the channel such that the solvent passes through the porous substance.

As solvent passes through the substance, the solvent will dissolve the substance to form a working solution. The rate at which the solvent is passed through the 5 substance determines the concentration of the substance in solution in the solvent that has passed through the porous solid substance. Hence, the rate of solvent flow is controlled to achieve a working solution of desired concentration.

The channel in which the substance is provided is sufficiently narrow so that 10 dissolution of the substance is diffusion limited.

The working solution may be used as a reactant or as a calibration standard.

When the desired volume of the working solution has been prepared, the solvent can 15 be drained from the channel holding the solid substance. If required, the process can be repeated. As dissolution is diffusion limited, subsequent working solutions of the same concentration can be produced by reproducing the rate of flow of the solvent.

It will be appreciated that the third method may be varied. For example, instead of 20 using a porous solid, the substance used to make the working solution may be immobilized in a slow release gel. (The use of a slow release gel is not in accordance

( with the current invention.) The working solution could be prepared by bringing a predetermined volume of a solvent into contact with the slow release gel and leaving the solvent in contact with the slow-release gel for a predetermined duration during which the substrate dissolves to form the working solution. The solvent is then 5 removed from contact with the gel. By controlling the duration of the contact between the solvent and the slow-release gel, working solutions of different concentrations may be prepared.

It will be appreciated that the three methods described above need not be used 10 together. In particular, the third method may be used with chemical devices that are not manufactured by either the first or second methods.

Further aspects of the invention are set out in the following clauses.

a) A method of preparing a working solution of a substance at a desired concentration in a chemical device comprising, providing a substance in a soluble 5 form in a chemical device, contacting the substance with a solvent for the substance in the device, and controlling said contact between the substance and the solvent so as to produce a working solution of the substance in the solvent at a concentration dependent on said control.

10 b) A method according to clause a), wherein said contacting comprises moving the solvent past the substance so as to contact the substance, said controlling of the contact comprising controlling the rate of movement of the solvent.

c) A method according to clause a), wherein said contacting comprises 15 contacting a volume of the solvent with the substance and leaving the solvent and the substance in contact for a controlled duration before separating the substance and the solvent. d) A method according to any one of clauses a) to c), in which after said 20 contacting, the solvent and the substance are separated, the substance then being contacted with a further solvent for the substance, said contact between the substance

and the further solvent being controlled so as to produce a working solution of the substance in the further solvent at a concentration dependent on said control of the contact between the substance and the further solvent.

5 e) A method according to clause d), wherein the further solvent has the same composition as the first mentioned solvent.

fl A method according to any one of clauses a) to e), wherein the substance is a porous solid.

g) A method according to clause f), when dependent on clause b), wherein the solvent is passed through the substance.

h) A method according to any one of clauses a) to e), wherein the substance 15 is a gel or immobilized in a gel.

i) A method according to any one of clauses a) to h), wherein the working solution of the substance in the solvent is then used in the chemical device for calibration.

- - j) A method according to any one of clauses a) to h), wherein the working solution of the substance is then reacted in the chemical device.

k) A method according to any one of clauses a) to j), wherein the chemical 5 device is a chip-type chemical device.

Claims

(.T.AIMS

1. A method of preparing a working solution of a substance at a desired concentration in a chemical device comprising, providing a substance in a soluble form in a chemical device, contacting the substance with a solvent for the substance 5 in the device, and controlling said contact between the substance and the solvent so as to produce a working solution of the substance in the solvent at a concentration dependent on said control, and wherein the substance is a porous solid.

2. A method according to claim 1, wherein said contacting comprises moving 10 the solvent past the substance so as to contact the substance, said controlling of the contact comprising controlling the rate of movement of the solvent.

3. A method according to claim 1, wherein said contacting comprises contacting a volume of the solvent with the substance and leaving the solvent and the 15 substance in contact for a controlled duration before separating the substance and the solvent.

4. A method according to any one of claims 1 to 3, in which after said contacting, the solvent and the substance are separated, the substance then being 20 contacted with a further solvent for the substance, said contact between the substance and the further solvent being controlled so as to produce a working solution of the

substance in the further solvent at a concentration dependent on said control of the contact between the substance and the further solvent.

5. A method according to claim 4, wherein the further solvent has the same 5 composition as the first mentioned solvent.

6. A method according to claim 2, wherein the solvent is passed through the substance. 10

7. A method according to any one of claims 1 to 6, wherein the working solution of the substance in the solvent is then used in the chemical device for calibration.

8. A method according to any one of claims 1 to 6, wherein the working 15 solution of the substance is then reacted in the chemical device.

9. A method according to any one of claims 1 to 8, wherein the chemical device is a chip-type chemical device.