WO2000000630A1 - Droplet reaction chamber - Google Patents
Droplet reaction chamber Download PDFInfo
- Publication number
- WO2000000630A1 WO2000000630A1 PCT/US1998/012808 US9812808W WO0000630A1 WO 2000000630 A1 WO2000000630 A1 WO 2000000630A1 US 9812808 W US9812808 W US 9812808W WO 0000630 A1 WO0000630 A1 WO 0000630A1
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- WO
- WIPO (PCT)
- Prior art keywords
- chamber
- droplet
- reaction
- reactant
- reaction chamber
- Prior art date
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/686—Polymerase chain reaction [PCR]
Definitions
- the present invention relates in general to chambers for chemical reactions, and in particular to the construction of such chambers by application of a fluoropolymer (polymer containing fluoro group) , such as Polytetrafluoroethylene (PTFE) to aqueous solutions.
- a fluoropolymer polymer containing fluoro group
- PTFE Polytetrafluoroethylene
- the invention described and claimed herein comprises a novel chemical reaction chamber for carrying out reactions in aqueous solutions, characterized by an outer coating of a fluoropolymer such as PTFE.
- a solid insoluble material like active charcoal, metal powder, silica powder or a small piece of membrane or any other material is inserted inside or on the surface of the droplet reaction chamber, it will remain inside or on the surface .
- liquid By using a micrc-pipette, liquid can be easily transferred from one droplet reaction chamber to another.
- the sizes of the droplets can be increased or decreased using a micropipette and eventually either by adding or removing the solution to/from the droplet reaction chamber.
- droplet reaction chambers can be used for different applications in chemical and biochemical reactions. In research laboratories, there are very often situation, when the container of the fluid can create problems while working with small volumes (in microliter range) .
- the droplet reaction chambers can be prepared in larger sizes by simply shaking the aqueous solution with the PTFE powder.
- a chemical reaction comprising an aqueous solution coated with a fluoropolymer, such as PTFE powder.
- a fluoropolymer such as PTFE powder.
- Figures la and lb are a plan view of a droplet reaction chamber, contrasting an untreated droplet ( Figure la) with a treated to form a droplet reaction chamber ( Figure lb) .
- Figure 2 illustrates a droplet reaction chamber with a membrane .
- Figure 3 illustrates a droplet reaction chamber with solid particles .
- Figures 4a and 4b illustrate the fusion of two droplet reaction chambers (Figure 4a) into a single droplet reaction chamber ( Figure 4b) .
- the invention is a novel chemical reaction chamber for carrying out reactions in aqueous solutions, characterized by an outer coating of a fluoropolymer, shown in overview in Figure 1.
- a fluoropolymer shown in overview in Figure 1.
- the operation of the invention is described with reference to a commonly available, inexpensive fluoropolymer, the perfluorocarbon PTFE, available from DuPont under the tradename TEFLONTM. It has been found that a preferred particle size is less than 500 microns. This is by way of illustration only, and the invention could be implemented using any suitable fluoropolymer .
- an aqueous solution (1) normally spreads on the support surface (2) .
- aqueous solution containing reactants of interest (3) is coated with a coating layer (4) of PTFE, such as DuPont TEFLONTM, it forms a droplet reaction chamber (5) .
- the coating (4) causes the aqueous solution (3) to remain stably in a defined volume without the need for any external solid wall (except for a support ⁇ 2 ⁇ ).
- molecules which increase the surface tension of aqueous solution can enhance the formation of hydrogen binding between fluorine atoms of PTFE and OH-group of water.
- solutes such as ionic salts increases the surface tension of aqueous solutions as compared to the surface tension of pure water.
- this increase of surface tension by addition of ionic salts is significantly smaller as compared to the decrease in surface tension by addition of detergents or alcohol. Therefore, materials which do not contain OH- or other groups that negatively influence the surface tension of aqueous solutions, will be suitable as supports for droplet reaction chambers.
- PTFE is an ideal substance for the described uses, since it is non-toxic, chemically inert, and able to withstand extremes of heat and cold.
- the reactants may be combined, then coated, or one reactant may be coated, and additional reactants introduced through the PTFE layer (4).
- One method of doing so is by insertion using a pipette (6) .
- a sample of the reaction product may be withdrawn through the PTFE layer (4), using for example a pipette.
- the droplet reaction chamber (5) may contain solid particles, such as activated charcoal, a solid matrix for affinity purification, enzyme bound beads for biochemical reactions, cells or tissue, either within (7) the droplet reaction chamber (5) or on its surface (8. Further processing of the droplet reaction chamber is possible. Examples including electrophoration, electroelution and electrochemical reactions, which may be accomplished by simply placing the droplet reaction, chamber between electrodes. Addition of metallic powder to the droplet reaction chamber increases the current flow through the chamber.
- the results of the chemical reaction may likewise be further processed, for example as follows.
- the droplet reaction chamber may be destroyed either by the addition of a detergent, an organic solvent or any other substance that reduces surface tension.
- the PTFE coating may then be removed from aqueous component by centrifugation, leaving the reaction product .
- the droplet reaction chamber may be dried and subsequently reformed by the addition of water.
- Example 1 Use as a chemical or biochemical reaction chamber.
- a droplet reaction chamber By pipetting an aqueous solution, buffer or reaction mixture on PTFE powder, a droplet reaction chamber is formed.
- the droplet reaction chamber can be broken in different aliquots without the loss of materials.
- the reactions inside the droplet reaction chamber can be started or blocked by pipetting appropriate chemicals, such as biochemicals, enzymes or inhibitors, into the droplet reaction chamber.
- the droplet reaction chamber can be centrifuged in a container containing a filter having pores smaller than the particle size of the PTFE.
- Example 2 Application in Equilibrium Dialysis
- a membrane (9) is placed on a droplet reaction chamber (5) , it floats along with the droplet reaction chamber (5) .
- the lower surface of the membrane will be in contact with the liquid inside the droplet reaction chamber.
- a Liquid (10) may then be placed on the upper side of the membrane for the dialysis.
- a sample may be taken from either side of the membrane using fcr example a micropipette.
- the droplet reaction chamber may be used as a disposable dialyser for small sample.
- two or more reactants may be combined as follows. Each reactant is coated with PTFE as described above. The resulting droplet reaction chambers may then be combined by forcing them together, resulting in rapid mixing of their contents.
- two reactants are coated to form droplet reaction chamber 11 and 12, then combined to form droplet reaction chamber 13, in which a reaction between the contents of droplet reaction chamber 11 and 12 will occur, as shown in Figure 4b.
- Example 5 Application in Tissue Culture Experiments Many natural cells and cell lines have a tendency to stick to the surface of containers. By using gently shaking a mixture of an aqueous solution containing such cells with PTFE powder, the tendency to stick is reduced. Cells may be grown inside the PTFE coated aqueous phase suspension. In some cases, cell growth may be improved because of the three dimensional nature of the aqueous phase. A gentle shaking of the tissue culture container can evenly distribute the cells inside the chamber.
Abstract
A reaction chamber is constructed of a reactant-containing aqueous solution (1), which may be in droplet form, coated with a fluoropolymer powder such as Polytetrafluoroethylene (PTFE). Using micropipette, size of the droplet chamber (5) is increased or decreased by removing or adding liquid. A droplet chamber (5) containing a first reactant such as an enzyme-bound bead is combined with a second droplet chamber containing a second reactant to react the first and second reactants. A dialysis chamber contains a filtration membrane in contact with the droplet chamber (5). Placing the droplet chamber (5) between two electrodes and producing current flow between the electrodes provides an electrochemical reaction. A temperature-sensitive reaction such as Polymerase Chain Reaction (PCR) can be performed by heating or cooling the droplet chamber (5). In tissue culture, coating (4) a solution containing tissue cells with the fluoropolymer powder reduces sticking of the cells to the surfaces of a container.
Description
TITLE: DROPLET REACTION CHAMBER
FIELD AND BACKGROUND of THE INVENTION
FIELD OF THE INVENTION
The present invention relates in general to chambers for chemical reactions, and in particular to the construction of such chambers by application of a fluoropolymer (polymer containing fluoro group) , such as Polytetrafluoroethylene (PTFE) to aqueous solutions.
The invention described and claimed herein comprises a novel chemical reaction chamber for carrying out reactions in aqueous solutions, characterized by an outer coating of a fluoropolymer such as PTFE.
BACKGROUND INFORMATION
Chemical (including biochemical) reactions are frequently carried out within a chamber or other container. In chemical and biochemical experiments, especially those involving small volumes (microvolumes) of a sample, there is always a significant loss of the sample as it disperses on the container walls.
Additionally, in reactions which are temperature sensitive, as for example the Polymerase Chain Reaction (PCR), there is also a loss of energy and time resulting from the need to heat (or cool) the reaction chamber itself.
However, when water or an aqueous solution contacts PTFE powder, it forms droplets coated with the powder. These droplets form a reaction chamber which does not involve significant loss of sample or significant energy or time loss from the heating or cooling of a reaction chamber.
If a solid insoluble material like active charcoal, metal powder, silica powder or a small piece of membrane or any other material is inserted inside or on the surface of the droplet reaction chamber, it will remain inside or on the surface .
By using a micrc-pipette, liquid can be easily transferred from one droplet reaction chamber to another. The sizes of the droplets can be increased or decreased using a micropipette and eventually either by adding or removing the solution to/from the droplet reaction chamber.
These droplet reaction chambers can be used for different applications in chemical and biochemical reactions. In research laboratories, there are very often situation, when the container of the fluid can create problems while working with small volumes (in microliter range) . The droplet reaction chambers can be prepared in larger sizes by simply shaking the aqueous solution with the PTFE powder.
OBJECTS
The foregoing problem is overcome, and other advantages are provided by a chemical reaction comprising an aqueous solution coated with a fluoropolymer, such as PTFE powder.
Among the objects of the present invention are to provide a new and useful chemical reaction chamber which does not rely on conventional walls to contain the chemical reaction and thereby to provide a new and useful chemical reaction which reduces loss of reactants and reduces the energy and time required to heat or cool the reaction.
These and other objects which will be apparent from the discussion which follows are achieved, in accordance with the invention, by providing a novel chemical reaction chamber for carrying out reactions in aqueous solutions, characterized by an outer coating of a fluoropolymer, such as PTFE.
The various features of novelty which characterize the invention are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its advantages and objects, reference is made to the accompanying drawings and descriptive matter in which a preferred embodiment of the invention is illustrated.
BRIEF DESCRIPTION OF THE DRAWING
The foregoing and still other objects of this invention will become apparent, along with various advantages and features of novelty residing in the present embodiments, from study of the following drawings, in which:
Figures la and lb are a plan view of a droplet reaction chamber, contrasting an untreated droplet (Figure la) with a treated to form a droplet reaction chamber (Figure lb) .
Figure 2 illustrates a droplet reaction chamber with a membrane .
Figure 3 illustrates a droplet reaction chamber with solid particles .
Figures 4a and 4b illustrate the fusion of two droplet reaction chambers (Figure 4a) into a single droplet reaction chamber (Figure 4b) .
DESCRIPTION OF THE PREFERED EMBODIMENT
Referring to the drawings, the invention is a novel chemical reaction chamber for carrying out reactions in aqueous solutions, characterized by an outer coating of a fluoropolymer, shown in overview in Figure 1. The operation of the invention is described with reference to a commonly available, inexpensive fluoropolymer, the perfluorocarbon PTFE, available from DuPont under the tradename TEFLON™. It has been found that a preferred particle size is less than 500 microns. This is by way of illustration only, and the invention could be implemented using any suitable fluoropolymer . As shown in Figure la, an aqueous solution (1) normally spreads on the support surface (2) . However, when an aqueous solution containing reactants of interest (3) is coated with a coating layer (4) of PTFE, such as DuPont TEFLON™, it forms a droplet reaction chamber (5) .
The coating (4) causes the aqueous solution (3) to remain stably in a defined volume without the need for any external solid wall (except for a support {2}).
The explanation of the operation of the invention is believed to be as follows. Due to their high affinity to form hydrogen binding, the terminal fluorine atoms in a fluoropolymer, such as PTFE, form hydrogen bonds with H-atom of water thus increasing the surface tension of the aqueous phase and enabling the formation of spherical droplets. This explanation is reinforced by the observation that the addition of alcohol or detergents tc the aqueous phase destroys the droplet reaction chamber. It is believed that the addition of alcohol decreases the hydrogen-binding of H-atoms of water with fluorine atoms of PTFE, thus lowering the surface tension of the aqueous phase and resulting in disappearance of the droplet reaction chamber. Furthermore, it has been observed that the formation of droplet reaction chambers does not take place on the surfaces that contain OH-, or similar groups on the surface and thus would disturb the hydrogen-bonding of PTFE and water., for example, glass. Similarly, detergents lower the surface tension of aqueous phase and have a tendency to accumulate preferentially at the surface thus reducing the formation of hydrogen-bonds between fluorine atoms of PTFE And hydrogen atoms of water. Therefore, addition of any substance which reduces the surface tension will reduce or completely hinder the formation of droplets.
On the other hand, molecules which increase the surface tension of aqueous solution can enhance the formation of hydrogen binding between fluorine atoms of PTFE and OH-group of water. For example, solutes such as ionic salts increases
the surface tension of aqueous solutions as compared to the surface tension of pure water. However, this increase of surface tension by addition of ionic salts is significantly smaller as compared to the decrease in surface tension by addition of detergents or alcohol. Therefore, materials which do not contain OH- or other groups that negatively influence the surface tension of aqueous solutions, will be suitable as supports for droplet reaction chambers.
PTFE is an ideal substance for the described uses, since it is non-toxic, chemically inert, and able to withstand extremes of heat and cold.
The reactants may be combined, then coated, or one reactant may be coated, and additional reactants introduced through the PTFE layer (4). One method of doing so is by insertion using a pipette (6) .
Similarly, a sample of the reaction product may be withdrawn through the PTFE layer (4), using for example a pipette.
Referring to Figure 3, in addition to reactants, the droplet reaction chamber (5) may contain solid particles, such as activated charcoal, a solid matrix for affinity purification, enzyme bound beads for biochemical reactions, cells or tissue, either within (7) the droplet reaction chamber (5) or on its surface (8. Further processing of the droplet reaction chamber is possible. Examples including electrophoration, electroelution and electrochemical reactions, which may be accomplished by simply placing the droplet reaction, chamber between electrodes. Addition of metallic powder to the droplet
reaction chamber increases the current flow through the chamber.
The results of the chemical reaction may likewise be further processed, for example as follows. The droplet reaction chamber may be destroyed either by the addition of a detergent, an organic solvent or any other substance that reduces surface tension. The PTFE coating may then be removed from aqueous component by centrifugation, leaving the reaction product .
Alternatively, the droplet reaction chamber may be dried and subsequently reformed by the addition of water.
Specific applications of the invention will now be illustrated.
Example 1. Use as a chemical or biochemical reaction chamber.
By pipetting an aqueous solution, buffer or reaction mixture on PTFE powder, a droplet reaction chamber is formed. The droplet reaction chamber can be broken in different aliquots without the loss of materials. The reactions inside the droplet reaction chamber can be started or blocked by pipetting appropriate chemicals, such as biochemicals, enzymes or inhibitors, into the droplet reaction chamber. Once the reaction is completed, the droplet reaction chamber can be centrifuged in a container containing a filter having pores smaller than the particle size of the PTFE.
Example 2 . Application in Equilibrium Dialysis
Referring to Figure 2, if a membrane (9) is placed on a droplet reaction chamber (5) , it floats along with the droplet reaction chamber (5) . The lower surface of the membrane will be in contact with the liquid inside the droplet reaction chamber. A Liquid (10) may then be placed on the upper side of the membrane for the dialysis. Once equilibrium has been reached, a sample may be taken from either side of the membrane using fcr example a micropipette. Thus, the droplet reaction chamber may be used as a disposable dialyser for small sample.
Example 3. Combining Multiple Reaction Chambers
Referring to Figure 4, two or more reactants may be combined as follows. Each reactant is coated with PTFE as described above. The resulting droplet reaction chambers may then be combined by forcing them together, resulting in rapid mixing of their contents. In Figure 4a, two reactants are coated to form droplet reaction chamber 11 and 12, then combined to form droplet reaction chamber 13, in which a reaction between the contents of droplet reaction chamber 11 and 12 will occur, as shown in Figure 4b.
Example 4. Rapid Temperature Change.
In some reactions, notably PCR, it is necessary to rapidly vary the temperature of the reactants. Using a droplet reaction chamber, the heat and time otherwise expended on changing the temperature of a solid container is necessary.
Example 5. Application in Tissue Culture Experiments
Many natural cells and cell lines have a tendency to stick to the surface of containers. By using gently shaking a mixture of an aqueous solution containing such cells with PTFE powder, the tendency to stick is reduced. Cells may be grown inside the PTFE coated aqueous phase suspension. In some cases, cell growth may be improved because of the three dimensional nature of the aqueous phase. A gentle shaking of the tissue culture container can evenly distribute the cells inside the chamber.
As can be seen from the above description and examples, it is possible to carry out a wide variety of chemical and biochemical reactions using the invention, simply providing appropriately sized droplets of an aqueous solution containing the desired reactants and by coating the droplets with PTFE.
Thus, there has been described a novel chemical reaction chamber for carrying out reactions in aqueous solutions, characterized by an outer coating of PTFE, that has a number of novel features, and a manner of making and using the invention.
While a specific embodiment of the invention has been shown and described in detail to illustrate the application of the principles of the invention, it will be understood that the invention may be embodied otherwise without departing from such principles and various modifications, alternate constructions, and equivalents will occur to those skilled in the art given the benefit of this disclosure. Thus, the invention is not limited to the specific embodiment described herein, but is defined by the appended claims.
Claims
1. A chamber for carrying out chemical reactions in aqueous solution, comprising a droplet reaction chamber, said droplet reaction chamber comprising: an aqueous solution containing at least one reactant in droplet form; and a coating of a fluoropolymer powder on the said droplet, which maintains said aqueous solution in droplet form.
2. A chamber as in claim 1, further comprising a support for supporting said droplet reaction chamber.
3. A chamber as in claim 1 wherein said fluoropolymer powder is Polytetrafluoroethylene (PTFE) .
4. A chamber as in claim 1 wherein said fluoropolymer has a particle size of less than 500 micrometer.
5. A dialysis chamber comprising a droplet reaction chamber as in claim 1 and further comprising a filtration membrane in contact with said droplet reaction chamber
6. A method for carrying out chemical reaction, comprising the steps of: providing a first chamber as in claim 1 wherein said chamber contains a first reactant; providing a second chamber as in claim 1 wherein said chamber contains a second reactant; and combining the chambers .
7. A method as in claim 6 wherein said first reactant comprises an enzyme-bound bead.
8. A kit for carrying out chemical reactions comprising a fluoropolymer powder, a container and reagents.
9. A method for tissue culture comprising the steps of: providing an aqueous solution containing biological cells in a container and coating said solution with a fluoropolymer powder whereby sticking of the cells is reduced to the container surface in contact with said solution.
10.A method for carrying out a temperature-sensitive chemical reaction, comprising the step of: providing a chamber containing a reactant as in claim 1 and heating or cooling said chamber to carry out said chemical reaction.
11.A method as in claim 10 wherein said temperature-sensitive chemical reaction is Polymerase Chain Reaction (PCR) .
12.A method for chemical processing the steps of: providing a chamber containing a reactant as in claim 1; reacting said reactant to carry a chemical process within said chamber; destroying said chamber by adding a chamber- destroying substance; and removing the fluoropolymer powder by filtration and centrifugation.
13.A method as in claim 12 wherein said chamber- destroying substance is a detergent.
14.A method as in claim 12 wherein said chamber-destroying substance is an organic solvent.
15.A method for carrying out an electrochemical process comprising the step of: providing a droplet reaction chamber as in claiml; placing said droplet chamber between electrodes; and providing a current flow between the two electrodes to produce an electrochemical reaction.
16. A method as in claim 15 wherein said electrochemical process comprises electrophoration.
17. A method as in claim 15 wherein said electrochemical process comprises electroelution.
18. A method as in claim 15 further comprising the step of placing metal particles within or on the surface of said droplet reaction chamber.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1998/012808 WO2000000630A1 (en) | 1998-06-26 | 1998-06-26 | Droplet reaction chamber |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1998/012808 WO2000000630A1 (en) | 1998-06-26 | 1998-06-26 | Droplet reaction chamber |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2000000630A1 true WO2000000630A1 (en) | 2000-01-06 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1998/012808 WO2000000630A1 (en) | 1998-06-26 | 1998-06-26 | Droplet reaction chamber |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2000000630A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6977145B2 (en) | 1999-07-28 | 2005-12-20 | Serono Genetics Institute S.A. | Method for carrying out a biochemical protocol in continuous flow in a microreactor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5374397A (en) * | 1992-11-02 | 1994-12-20 | Termin; Andreas P. | Device for measurement of no contents |
| US5401634A (en) * | 1986-08-07 | 1995-03-28 | Minnesota Mining And Manufacturing Company | Stable biologically active fluorochemical emulsions |
| US5466570A (en) * | 1995-02-21 | 1995-11-14 | Eastman Kodak Company | Sonic micro reaction zones in silver halide emulsion precipitation process |
-
1998
- 1998-06-26 WO PCT/US1998/012808 patent/WO2000000630A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5401634A (en) * | 1986-08-07 | 1995-03-28 | Minnesota Mining And Manufacturing Company | Stable biologically active fluorochemical emulsions |
| US5374397A (en) * | 1992-11-02 | 1994-12-20 | Termin; Andreas P. | Device for measurement of no contents |
| US5466570A (en) * | 1995-02-21 | 1995-11-14 | Eastman Kodak Company | Sonic micro reaction zones in silver halide emulsion precipitation process |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6977145B2 (en) | 1999-07-28 | 2005-12-20 | Serono Genetics Institute S.A. | Method for carrying out a biochemical protocol in continuous flow in a microreactor |
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