Patent Application
20240309436
The present invention relates to a method and apparatus for processing a biological sample to detect the presence of a plurality of biomolecules, or a plurality of sequences within a biomolecule or biomolecules. The processing comprises pre-amplification and/or amplification steps on the sample within a cartridge.
Compact sequencing devices allow biomolecules to be detected outside of a lab environment. These devices enable real time detection of DNA,RNA or proteins using a streamlined workflow without the need for additional, specialized equipment or technicians.
One example of such a system is disclosed in WO2018055407. The system is suitable for the detection of DNA (or RNA) in a sample of biological material. The system comprises a test cartridge and a base unit for controlling the operation of the test cartridge. The test cartridge contains reagents in chambers for preparing a sample for amplification. Once a sample is inserted in the test cartridge, the reagents are mixed with the sample by transferring the reagents between the chambers. All of the sample preparation steps, including lysing, washing and elution, take place within the cartridge itself. Following this, the sample is transferred to an amplification unit within the test cartridge to detect DNA in real time by e.g. PCR (polymerase chain reaction).
PCR reactions work by amplifying a target strand of DNA in a sample over a series a cycles. The amplified strands of DNA contain fluorescent reporter dyes so that the presence of the target strand can be confirmed. PCR reactions must be performed using alternating temperature steps. Other DNA amplification techniques are available such as LAMP (loop-mediated isothermal amplification), which carries out amplification over a constant temperature. Since LAMP amplifies a target strand with high specificity and without the need for expensive reagents or instruments, it is especially useful for diagnostic testing.
The coronavirus pandemic has highlighted the need for rapid diagnostic testing in both the home and clinical settings. In order to detect viral RNA, RT-PCR (reverse transcriptase-PCR) or RT-LAMP (reverse transcriptase-LAMP) amplification must be used. These techniques are similar to PCR and LAMP except that they first begin by performing reverse transcription of the RNA in order to obtain DNA. The procedure then continues by amplifying the DNA using the PCR or LAMP method.
While RT-PCR testing is considered to be the most sensitive type of test for COVID, the results of consumer tests are usually received days after the sample is taken. Due to the obvious need to reduce the spread of infection, it is preferable that results are received as soon as possible. It would also be desirable to rapidly diagnose the presence of other pathogens that can rapidly outbreak in a population, such as Strep-A.
As well as diagnostic testing to confirm to presence of a pathogen, it is also desirable that the results of genotyping are received as quickly as possible. Genotyping is the determination of variants in the genetic make-up of a subject. SNP genotyping is the measurement of genetic variations of single nucleotide polymorphisms (SNPs), which are mutations at a specific base pair mutation at a specific point of the genome. SNP genotyping can provide insights into predispositions an individual might have for certain diseases. Due to the life-changing impact that the results of such tests can have for an individual, it is desirable that results of such tests are received quickly.
According to a first aspect there is provided a method of analysing a sample containing biological cells to detect the presence of a plurality of biomolecules, or a plurality of sequences within a biomolecule or biomolecules, the method comprising: lysing the sample to obtain a lysed sample; introducing the lysed sample into a sample chamber of a disposable cartridge; mixing the lysed sample with a dilution buffer in the sample chamber to obtain a first mixture; displacing at least a part of the first mixture from the sample chamber to an analysis unit comprising first and second pluralities of wells, wherein the first mixture fills the first plurality of wells; causing the analysis unit to perform isothermal or thermo-cycled pre-amplification on the first mixture in the first plurality of wells to generate a second mixture; displacing at least a part of the second mixture from the first plurality of wells to the second plurality of wells; and causing the analysis unit to perform an isothermal or thermo-cycled amplification stage on the second mixture within the second plurality of wells and identifying the presence of said plurality of biomolecules or sequences, or of a plurality of second biomolecules or sequences derived from the first mentioned plurality of biomolecules or sequences.
Optionally, the pre-amplification is an isothermal pre-amplification, for example LAMP amplification, and the amplification is a thermo-cycled amplification, for example PCR amplification.
Optionally, the second plurality of wells are configured to perform a plurality of spatially multiplexed assays for different biomolecules or sequences within biomolecules.
Optionally, the first pluralities of wells contain a pre-amplification mastermix and the second plurality of wells contain an amplification mastermix.
Optionally, said step of displacing includes diluting the second mixture with a dilution buffer.
Optionally, the sample is lysed by: introducing said sample into a discrete container that is prefilled with a lysis buffer; agitating the container to assist with lysing to release biomolecules; extracting lysed sample from the container.
Optionally, the steps are performed in sequence and without any intervening elution and/or washing steps.
According to a second aspect there is provided a method of analysing a sample containing biological cells to detect the presence of a plurality of biomolecules, or a plurality of sequences within a biomolecule or biomolecules, the method comprising: lysing the sample to obtain a lysed sample; introducing the lysed sample into a sample chamber of a disposable cartridge; mixing the lysed sample with a dilution buffer in the sample chamber to obtain a first mixture; displacing at least a part of the first mixture from the sample chamber to an analysis unit comprising a pluralities of wells, wherein the first mixture fills the plurality of wells; causing the analysis unit to perform one of isothermal or thermo-cycled pre-amplification on the first mixture in the plurality of wells to generate a second mixture; and causing the analysis unit to perform the other of isothermal or thermo-cycled amplification stage on the second mixture within the plurality of wells and identifying the presence of said plurality of biomolecules or sequences, or of a plurality of second biomolecules or sequences derived from the first mentioned plurality of biomolecules or sequences.
Optionally, the pre-amplification is an isothermal pre-amplification, for example LAMP amplification, and the amplification is a thermo-cycled amplification, for example PCR amplification.
According to a third aspect there is provided a method of analysing a sample containing biological cells to detect the presence of a plurality of biomolecules, or a plurality sequences within a biomolecule or biomolecules, the method comprising: lysing the sample to obtain a lysed sample; introducing the lysed sample into a sample chamber of a disposable cartridge; mixing the lysed sample with a dilution buffer in the sample chamber to obtain a first mixture; displacing at least a part of the first mixture to a first mastermix chamber containing a pre-amplification mastermix; causing an isothermal or thermo-cycled pre-amplification of the first mixture within the first mastermix chamber to generate a second mixture; optionally, displacing at least a part of the second mixture to a second mastermix chamber containing an amplification mastermix to generate a third mixture; displacing at least a part of the third mixture from the second mastermix chamber, or the second mixture from the first mastermix chamber, to an analysis unit comprising a plurality of wells; and causing the analysis unit to perform an isothermal or thermo-cycled amplification stage on the second or third mixture and identifying the presence of said plurality of biomolecules or sequences, or of a second plurality of biomolecules or sequences derived from the first mentioned plurality of biomolecules or sequences.
Optionally, the pre-amplification is an isothermal pre-amplification, for example LAMP amplification, and the amplification is a thermo-cycled amplification, for example PCR amplification.
Optionally, the first mastermix chamber is caused to heat the first mixture during pre-amplification.
According to a fourth aspect there is provided a method of analysing a sample containing biological cells to detect the presence of a plurality of biomolecules, or a plurality sequences within a biomolecule or biomolecules, the method comprising: introducing said sample into a discrete container that is prefilled with a lysis buffer; agitating the container to assist with lysing to release biomolecules; extracting lysed sample from the container and introducing the lysed sample into a sample chamber of a disposable cartridge; mixing the lysed sample with a dilution buffer in the sample chamber to obtain a first mixture of lysed sample and dilution buffer; fluidly connecting the sample chamber to a mixing chamber of the disposable cartridge; displacing the first mixture from the sample chamber to the mixing chamber and performing a mixing on the first mixture; fluidly connecting the mixing chamber to a mastermix chamber of the disposable cartridge containing a mastermix; displacing the first mixture from the mixing chamber to the mastermix chamber to obtain a second mixture; displacing the second mixture from the mastermix chamber to an analysis unit comprising a plurality of wells; and causing the analysis unit to identify the presence of said plurality of biomolecules or sequences, or of a second plurality of biomolecules or sequences derived from the first mentioned plurality of biomolecules or sequences.
Optionally, said biomolecules are nucleic acids or proteins.
Optionally the method further comprises pre-amplifying parts of the biological molecules using PCR or LAMP.
Optionally, the sample is lysed in lysis buffer with a pH greater than 10.
Optionally, said step displacing the second mixture from the mastermix chamber to the analysis unit comprises: displacing the second mixture from the mastermix chamber back into the mixing chamber; fluidly connecting the mixing chamber to the analysis unit; and displacing the second mixture from the mixing chamber to the analysis unit.
Optionally, said sample chamber and said mastermix chamber are provided within an outer housing of a disposable cartridge, and said mixing chamber is provided within an inner housing of the disposable cartridge, the inner and outer housings being rotatable relative to one another about a central axis in order to facilitate said steps of fluidly connecting.
Optionally, displacement of mixtures between the various chambers is achieved by applying a positive or negative air pressure to the mixing chamber.
Optionally, the steps being performed in sequence and without any intervening elution and/or washing steps.
Optionally, said step of agitating the container comprises manually agitating the container.
Optionally, the analysis unit is releasable connected to the disposable cartridge.
According to a fifth aspect there is provided a method of analysing a sample containing biological cells to detect the presence of a plurality of biomolecules, or a plurality of sequences within a biomolecule or biomolecules, the method comprising: lysing the sample to obtain a lysed sample; introducing the lysed sample into a sample chamber of a disposable cartridge; mixing the lysed sample with a dilution buffer in the sample chamber to obtain a first mixture; incorporating a mastermix into the first mixture to produce a third mixture; performing amplification on the third mixture within a plurality of wells of an analysis unit; and identifying the presence of said plurality of biomolecules or sequences, or of a plurality of second biomolecules or sequences derived from the first mentioned plurality of biomolecules or sequences using assays relying on fluorescent dyes, wherein assays for different ones of the plurality of biomolecules or sequences are spatially multiplexed across the plurality of wells and multiplexed within given wells using different fluorescent dyes.
According to a sixth aspect there is provided a method of analysing a sample containing biological cells to detect the presence of a plurality of biomolecules, or a plurality of sequences within a biomolecule or biomolecules, the method comprising: preparing the sample for amplification; on a disposable cartridge including an analysis unit, causing heating of the prepared sample in order to perform a sequence of isothermal and thermo-cycled amplification steps; and identifying within the amplified sample, the presence of said plurality of biomolecules or sequences, or of a plurality of second biomolecules or sequences derived from the first mentioned plurality of biomolecules or sequences.
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
A system and method for processing a biological sample to perform detection of biomolecules contained in biological cells of a sample and, optionally, genetic testing or diagnostic testing will now be described. The system processes and analyses the sample in a relatively short time frame. Due to the speed with which the biological sample is processed and analysed, the system and method are particularly suitable for use in a non-medical environment such as the home or a retail premise, although medical uses are envisaged. The method and system aim to offer a relatively small physical footprint, be available at a relatively low cost, and be operable by a non-technical person such as a consumer or shop assistant.
The tube 1 is flexible and can be made of a plastic such as polypropylene. The tube 1 further comprises a cap 5 for closing an open end of the tube 1. The cap 5 has an opening for expelling droplets from the tube 1. The cap 5 may be suitable for, but not limited to, expelling droplets with a size of 25 ul+/−5 ul.
The tube 1 is pre-filled with a high pH buffer solution for lysing cells. Preferably, the buffer solution has a pH greater than 10, and more preferably between 12 and 14. In one example, the buffer solution is NaOH 37.48 mM and EDTA 0.2 mM. The tube 1 may further comprise an aluminium oxide membrane covering the opening of the cap 5. Droplets expelled through the opening of the cap 5 will be filtered through the membrane and the purity of the genetic material in the droplets can thereby be increased.
The test cartridge 70 comprises a multi-chamber unit 75 comprising a plurality of chambers 95a-i divided by radially extending walls. Each of the chambers is suitable for containing a sample and or reagents. In the example shown, chamber 95a receives a biological sample, chamber 95b contains a dilution buffer and chamber 95c comprises mastermix. An analysis unit 71 is installed in the analysis chamber 95d. In the present example, the analysis chamber 95b provides a vacant slot for receiving the analysis unit 71. The chambers are described in further detail below.
A spring 78 urges the frustoconical surface of the rotating chamber 74 against the opposed inner surface of the multi-chamber unit 75. A main opening 79 is provided in the frustoconical surface of the rotating chamber 48, and communicates with the flow through chamber thereof. A number of apertures 96 are formed around the inner surface of the multi-chamber unit, aligned with respective chambers. Each of these apertures is provided with an elastomeric O-ring 80 which provides sealing against the frustoconical surface of the rotating chamber. The apertures are configured such that the opening 79 in the frustoconical surface can be selectively aligned with apertures in the multi-chamber unit, whilst the O-ring seals prevent leakage from the unaligned apertures of the multi-chamber unit. In the illustrated test cartridge 70, the analysis chamber is not present. Rather, the analysis chamber is plugged into the vacant slot immediately prior to use.
Fluid can be moved between the rotating chamber 75 and chambers of the multi-chamber unit 74 using a syringe (pump) in the base unit to pneumatically move the liquids. This is illustrated in
Air is drawn by the syringe in the base unit through a path indicated by the series of arrows. This path comprises a rotatable coupling between the base unit and the flow through chamber within the cylindrical member 82. This negative pressure causes liquid to be drawn from the chamber of the multi-chamber unit, through the aligned apertures, into the flow through chamber within the cylindrical member 82.
When the rotating chamber 74 is filled with liquid, there may be a risk of liquid splashing upwards and then dropping down into the air flow paths connecting to the base unit. The rotating chamber may be provided with a two-way valve, sitting towards the upper end of the cylindrical member 82. This valve allows air to pass under pressure in both directions, i.e. into and out of the chamber, but prevents splashes from moving to the top of the chamber. The valve may be, for example, a “duck-bill umbrella” valve.
Referring again to the plan view of the test cartridge shown in
Chamber 1/Sample chamber (95a): The input chamber which receives the sample, e.g. by squeezing a drop of the sample from tube 1 through an inlet port (this is described in further detail below).
Chamber 2/Dilution buffer chamber (95b): Contains a dilution buffer to dilute the mixture of lysis buffer and sample in order to lower the pH of the mixture. NB. In the event of a reuse of a cartridge of the type described in WO2018055407, the buffer may be an elution buffer, merely for convenience.
Chamber 3/Mastermix chamber (95c): Contains mastermix beads or solution for preparing the sample for DNA or RNA amplification. The chamber 5c may also comprise desiccant beads.
In some embodiments, the sample undergoes pre-amplification and amplification stages. In these embodiments, two mastermix chambers may be provided in the cartridge, (e.g. chambers 95c an 95f), each respective mastermix chamber comprising the mastermix beads or solution for preparing the sample for pre-amplification or amplification respectively. As an alternative to providing two mastermix chambers, the mastermix for preparing the sample for pre-amplification may be provided in mastermix chamber 95c, and the mastermix for preparing the sample for amplification may be provided in a plurality of wells of the analysis unit.
Alternatively, in some embodiments, the mastermix for pre-amplification and amplification is provided in the plurality of wells of the analysis unit rather than in mastermix chambers of the cartridge.
In further embodiments, the mastermix chamber may be configured to perform isothermal pre-amplification on a sample contained in the mastermix chamber. In these embodiments, the mastermix chamber comprises a heating device to provide isothermal heating of the contents of the mastermix chamber.
Chamber 4/Analysis chamber (95d): This chamber contains a chip module which is configured to perform amplification in order to determine the presence of a genetic sequence.
Chamber 5/Waste-Vent chamber (95e): This chamber is empty prior to use, and is in liquid communication with a waste sump.
As shown in
The dilution buffer contained in chamber 95b can be any type of dilution buffer suitable for removing DNA and RNA from the solid phase such as de-ionised water or 10 mM Tris pH 8.5.
The mastermix comprises all of the reagents necessary for performing the chosen method of pre-amplification or amplification, apart from the primers and, in the case of PCR, a template. These additional components are provided within the amplification unit 71. When the amplification method is PCR, the mastermix can comprise, for example, Taq DNA Polymerase, dNTPs. MgCl2 a reaction buffer optimised for PCR and a fluorescent compound. A mastermix for LAMP can comprise a DNA polymerase, enzymes and a dye. When the amplification method is RT-PCR or RT-LAMP, the mastermix will also comprise a reverse transcriptase.
The above arrangement of chambers is only one possible arrangement that is suitable for analysing a sample comprising genetic material. In the present example, some of the chambers of the test cartridge 70 are redundant. Of course, other arrangements are envisaged in which more, or fewer, of the chambers are used in the workflow, and wherein different reagents are stored in any combination of the chambers partaking in the workflow.
The movement of fluid between the chambers of the test cartridge 70 is controlled by base unit 65, illustrated schematically in
The analysis unit 71 installed in the analysis chamber 95b comprises a chassis containing a plate having a plurality of wells comprising spotting reagents for performing amplification and detection of biomolecules such as DNA or RNA. The analysis unit may be configured to perform an isothermal or thermo-cycled pre-amplification stage and an isothermal or thermo-cycled amplification stage. Alternatively, an isothermal pre-amplification stage may be performed in the mixing chamber of the disposable cartridge and the analysis unit may be configured to perform an isothermal or thermo-cycled amplification stage only. The isothermal amplification may be LAMP and the thermo-cycled amplification stage may be PCR. In addition, or alternatively, the analysis unit may be configured to perform a multiplexed thermo-cycled or isothermal amplification using multi-dye detection. Visible results are produced from the amplification step to confirm the presence of specific sequences of DNA or RNA. It is also envisaged that in other embodiments, the analysis unit may be configured to detect biomolecules such as proteins.
The plurality of wells 84 may be divided into subsets such that each of the respective subsets comprise a respective set of primers specific for a respective target sequence. For example, a first subset of the array of wells may be spotted with a first set of primers specific for a first target genetic sequence, a second subset of the array of wells may be spotted with a second set of primers specific for a second target genetic sequence, and so on. In this way, the presence of a plurality of respective biomolecules or sequences can be detected. The specific primers spotted in a well may depend on whether the well is to be used for pre-amplification or amplification. A different set of primers for the pre-amplification and amplification steps may be required because the pre-amplification step may target a longer section of the genome than the section of genome targeted by the amplification step. Alternatively, the same primers may be used for pre-amplification and amplification.
In some embodiments, the plurality of wells 84 may also comprise a mastermix for preparing the sample for pre-amplification and/or a mastermix for preparing the sample for amplification. In embodiments where the pre-amplification and amplification occur in the same well, the mastermix for preparing the sample for pre-amplification and the mastermix for preparing the sample for amplification are contained in the same well. In other embodiments where the pre-amplification occurs in a first plurality wells and the amplification occurs in a second plurality of wells, the mastermix for preparing the sample for pre-amplification is contained in the first plurality of wells and the mastermix for preparing the sample for amplification is contained in the second plurality of wells. In other embodiments, the mastermix for preparing the sample for pre-amplification may be contained in a mastermix chamber of the cartridge and the mastermix for preparing the sample for amplification may be contained in the plurality of wells.
In order to fill the wills with liquid, a pressure needs to be applied in order to squeeze liquid into the wells. To achieve this, the base 85 of the wells is formed by a material that allows air to pass through but which is impermeable to liquid. Once the test cartridge 70 has been installed into the base unit, the optics 66 slid into place, and liquid transported in the analysis unit 71 so as to cover the array of wells, a linear actuator 86 is engaged with the Peltier module 72 in order to bias the bottom of the analysis chamber upwards, pressing the top of the analysis chamber against the bottom of the optics. This exerts a pressure on the liquid above the wells, forcing it into the wells in order to achieve satisfactory fill levels. This clamping pressure also ensures good thermal contact between the base of the analysis unit 71 and the Peltier module 72.
This mechanism for applying pressure above the wells to fill the wells is further illustrated in
In some cases it may be necessary to provide air flow channels into each of the chambers of the multi-chamber unit in order to allow liquid to flow in and out of the chambers. However, it is preferable that such channels are formed only at the time of use to avoid contamination.
The multi chamber unit 75 and intermediate component 87 are constructed of a suitable polymer such as Polypropylene, PTFE or COC. Advantageously, the intermediate component 87 may be made of a transparent polymer to allow a user to view certain steps in the analysis process. A barcode may be located on the outer surface of the top cover so the test cartridge 70 can be identified.
In one embodiment, illustrated in
Turning to
At 1100, the biological sample is lysed and introduced into the sample chamber of cartridge, which may be performed according to steps 100-300 of
At 1200, the lysed sample is mixed with a dilution buffer in the sample chamber to obtain a first mixture, which may be performed according to step 400 of
After step 1200, the following steps may be performed when at least part of the sample is mixed in the first mastermix chamber of the cartridge:
At 1250, the first mixture is displaced from the sample chamber to the mastermix chamber comprising a first mastermix for preparing the sample for pre-amplification,
At 1300, a pre-amplification stage is performed on first mixture in the first mastermix chamber to generate a second mixture.
At 1400, the second mixture is displaced from the first mastermix chamber to a second mastermix chamber comprising a second mastermix for preparing the sample for amplification.
At 1500, the second mixture is displaced to the analysis unit. The second mixture fills a second plurality of wells of the analysis unit and an amplification stage is performed on the second mixture.
Alternatively, after 1250, the method proceeds to 1350 where the first mixture is displaced from the mastermix chamber to the analysis unit. The first mixture fills a first plurality of wells of the analysis unit and a pre-amplification stage is performed on the first mixture to generate a second mixture. The method then proceeds to steps 1400 and 1500.
As a further alternative, after 1300, the method bypasses step 1400 and proceeds straight to step 1500. In this embodiment, the mastermix for preparing the sample for amplification is provided in the second plurality of wells of the analysis unit.
Alternatively, after step 1200, the following steps may be performed when the sample is not mixed in any mastermix chambers of the cartridge:
At 1350, first mixture is displaced from the sample chamber to the first plurality of wells of the analysis unit. The first plurality of wells contain a first mastermix for preparing the sample for pre-amplification. A pre-amplification stage is performed on first mixture in the first plurality of wells to generate a second mixture.
The method then proceeds directly to step 1500, where the second mixture is displaced from the first plurality of wells of the analysis unit to the second plurality of wells of the analysis unit. The second plurality of wells contain a second mastermix for preparing the sample for amplification. An amplification stage is performed on the second mixture in the second plurality of wells.
At 1600, the plurality of biomolecules or sequences, or of a plurality of second biomolecules or sequences derived from the first mentioned plurality of biomolecules or sequences, are identified.
It will be understood that any of the above described “displacing steps” involve the displacement of liquid from one chamber of the cartridge to one or more other chambers of the cartridge via the mixing chamber. The displacing steps are performed without any washing steps and there is no use of a frit.
Advantageously, by lysing the biological sample in a high pH buffer, cell lysis can take place in a matter of seconds. Further, by performing the lysis step outside of the test cartridge 70, fewer processing steps have to be conducted using the cartridge itself, which makes the cartridge workflow less time consuming. Since the lysis step can be easily performed by a consumer or subject, this step can be performed first and then presented to an operator of the test cartridge. It is noted that the lysis buffer is relatively non-toxic as far as the required reactions are concerned and therefore a washing step is unnecessary. In particular, the use of the toxic buffer guanidine hydrochloride is avoided.
In addition and surprisingly, as compared to the procedure described in WO2018055407, it has been found that the use of a frit to extract DNA from the lysed sample and hold it for washing is unnecessary. Rather, the lysed sample can be mixed first with the dilution buffer in the sample chamber, and the resulting combined sample transferred directly to a chamber containing the mastermix, before introducing the resulting mixture to the analysis chamber. The number of liquid transfer stages is significantly reduced. As each transfer stage can involve multiple operations of the syringe in the base unit to force air into and out of the mixing chamber, this represents a significant time saving. This in turn allows for more rapid genotyping and diagnostic testing and reduces the cross-infection risks. Indeed, as compared to the procedure described in WO2018055407, the sample preparation time, i.e. the time to provide the prepared sample to the AU once the lysed sample is introduced to the sample chamber, may be reduced from around 15 minutes to round 1.5 minutes.
Advantageously, by performing a pre-amplification stage followed by an amplification stage, it has been found that the total time to analyse the sample can be reduced without compromising sensitivity. For example, a pre-amplification stage of 10 minutes may be followed by an amplification stage of 5 minutes, or pre-amplification stage of 5 minutes may be followed by an amplification stage of 10 minutes, reducing the analysis time to only 15 minutes.
Although the processing steps before amplification could be considered a “crude” way to extract genetic material, the amounts of genetic material extracted by this method are sufficient to perform the amplification of the strands of DNA or RNA necessary for performing limited identification of a nucleic acid sequence or parts of such a sequence and, optionally, any SNP genotyping or diagnostic testing. The methods employed herein are thus sufficient for genotyping of specific SNPs, or for identifying genetic fragments specific for confirming the presence of certain pathogens in the biological sample.
Although the cartridge described herein comprises a central rotating chamber 75 surrounded by multiple chamber 95a-i, other designs are envisaged in which fewer chambers are used to prepare the sample for analysis.
This application is a continuation-in-part of U.S. patent application Ser. No. 18/184,615, filed Mar. 15, 2023. The entire contents of which is hereby incorporated by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 18184615 | Mar 2023 | US |
| Child | 18677287 | US |
