Legal claims defining the scope of protection. Each claim is shown in both the original legal language and a plain English translation.
1. A method for performing digital polymerase chain reaction (dPCR) in a dPCR biological analysis system including a thermal cycler, a processor, a detector, and a display, the method comprising: partitioning a biological sample volume including a plurality of target nucleic acids into a plurality of partitions, wherein at least one partition includes at least one target nucleic acid; amplifying, with the thermal cycler, the target nucleic acids in the plurality of partitions; generating, by the processor, a model for volume variation of the plurality of partitions based on a normal distribution of effective load volumes of the biological sample volume in the plurality of partitions; detecting, by the detector, the amplified target nucleic acids to determine a number of partitions including at least one target nucleic acid; calculating, by the processor, a concentration of target nucleic acids in the biological sample based on the model for volume variation and the number of partitions including at least one target nucleic acid; and displaying, on the display, the concentration of target nucleic acids in the biological sample.
This invention relates to digital polymerase chain reaction (dPCR) for biological analysis and addresses the problem of accurately determining nucleic acid concentrations in a sample. The method involves partitioning a biological sample containing target nucleic acids into numerous small compartments. Each compartment may or may not contain target nucleic acids. A thermal cycler then amplifies any target nucleic acids present within these compartments. A processor generates a model that accounts for variations in the effective volume of each compartment, assuming these variations follow a normal distribution. A detector identifies which compartments contain amplified target nucleic acids. Based on the number of compartments with amplified nucleic acids and the volume variation model, the processor calculates the concentration of target nucleic acids in the original biological sample. Finally, a display presents this calculated concentration.
2. The method of claim 1 , wherein the concentration of target nucleic acids in the biological sample is determined by using the equation: C = v 0 - v 0 2 + 2 σ 2 ln P ( neg ) σ 2 .
This invention relates to a method for quantifying target nucleic acids in a biological sample, addressing challenges in accurate nucleic acid detection and quantification. The method involves determining the concentration of target nucleic acids using a specific mathematical equation: C = v0 - (v0^2 + 2σ^2 * ln(P(neg)) / σ^2). Here, C represents the concentration of target nucleic acids, v0 is an initial volume or value, σ is a standard deviation, and P(neg) is the probability of a negative result. The equation accounts for variability in measurements, improving precision in nucleic acid quantification. The method likely builds on a broader process (described in claim 1) that involves sample preparation, amplification, or detection steps to isolate or detect the target nucleic acids before applying this equation. The invention aims to enhance the reliability of nucleic acid quantification, which is critical in applications like diagnostics, genetic testing, and research. The mathematical model corrects for noise or uncertainty in measurements, ensuring more accurate and reproducible results. This approach is particularly useful in scenarios where low concentrations of nucleic acids need to be detected with high confidence.
3. The method of claim 1 , wherein the concentration of target nucleic acids in the biological sample is determined by using the equation: P ( neg ) = erfc [ - 1 2 ( v 0 σ - C σ ) ] erfc [ - 1 2 ( v 0 σ ) ] e - Cv 0 + 1 2 σ 2 C 2 .
This invention relates to a method for quantifying target nucleic acids in a biological sample using statistical analysis. The method addresses the challenge of accurately determining nucleic acid concentrations in samples where detection is subject to variability, such as in low-abundance or noisy environments. The core technique involves applying an error function-based equation to calculate the probability of a negative detection event, which is then used to infer the concentration of target nucleic acids. The equation incorporates parameters including the observed signal (v0), the standard deviation of the signal (σ), and a concentration-dependent term (C). By solving this equation, the method provides a probabilistic estimate of nucleic acid concentration, accounting for measurement uncertainty. The approach is particularly useful in applications like molecular diagnostics, where precise quantification is critical but detection noise or sample variability may otherwise lead to inaccurate results. The method may be implemented in systems that perform nucleic acid amplification or sequencing, where signal variability is a common issue. The invention improves upon prior methods by incorporating a statistical framework that explicitly models detection errors, leading to more reliable concentration estimates.
4. The method of claim 1 , further comprising: amplifying the target nucleic acids to determine the number of partitions including at least one target nucleic acid.
This invention relates to nucleic acid analysis, specifically a method for quantifying target nucleic acids in a sample by partitioning the sample into multiple compartments and detecting the presence of target nucleic acids in each compartment. The method involves partitioning a sample containing target nucleic acids into a plurality of partitions, where each partition contains a known volume of the sample. The partitions are then analyzed to determine which partitions contain at least one target nucleic acid. To enhance detection sensitivity, the target nucleic acids in the partitions are amplified, allowing for the determination of the number of partitions that include at least one target nucleic acid. This amplification step improves the accuracy of quantifying the target nucleic acids by ensuring that even low-abundance targets are detectable. The method leverages statistical analysis of the partition data to infer the concentration of target nucleic acids in the original sample. This approach is particularly useful in applications requiring precise nucleic acid quantification, such as digital PCR or single-molecule analysis, where traditional bulk measurement techniques may lack sensitivity. The amplification step ensures that the detection of target nucleic acids is robust, even at low concentrations, providing a more reliable quantification of nucleic acid abundance in the sample.
5. The method of claim 1 , wherein the model for volume variation is: P ( neg ) = erfc [ - 1 2 ( v 0 σ - C σ ) ] erfc [ - 1 2 ( v 0 σ ) ] e - Cv 0 + 1 2 σ 2 C 2 .
This invention relates to a method for modeling volume variation in a system, addressing the challenge of accurately predicting changes in volume under varying conditions. The method employs a probabilistic model to estimate the likelihood of negative volume variation, incorporating key parameters such as an initial volume (v0), a standard deviation (σ), and a scaling factor (C). The model uses the complementary error function (erfc) to compute the probability of negative volume variation, accounting for statistical fluctuations and systematic biases. The formula integrates these parameters to provide a refined prediction, improving accuracy over traditional methods that may overlook dynamic interactions between variables. The approach is particularly useful in fields requiring precise volume control, such as fluid dynamics, material science, or manufacturing processes, where small deviations can significantly impact performance. By leveraging statistical functions and scaling factors, the method offers a robust framework for assessing volume stability and optimizing system design. The invention enhances predictive capabilities, enabling better decision-making in applications where volume consistency is critical.
7. The method of claim 1 , wherein the plurality of partitions is a plurality of reaction sites.
This invention relates to a method for performing chemical reactions in a partitioned system, addressing challenges in reaction control, efficiency, and scalability. The method involves dividing a reaction environment into multiple partitions, where each partition functions as an isolated reaction site. These reaction sites enable parallel or sequential reactions to occur independently, improving reaction specificity, reducing cross-contamination, and enhancing throughput. The partitions can be physical compartments, such as wells, chambers, or microchannels, or they can be virtual divisions within a continuous medium, such as droplets in a microfluidic system. The method allows for precise control over reaction conditions, such as temperature, pH, or reagent concentration, within each partition. This approach is particularly useful in high-throughput screening, combinatorial chemistry, and biochemical assays, where multiple reactions must be conducted simultaneously or in a controlled sequence. The partitions can be dynamically adjusted or reconfigured to accommodate different reaction requirements, further enhancing flexibility. The method ensures efficient use of reagents and minimizes waste, making it suitable for both laboratory and industrial applications.
8. The method of claim 1 , wherein the plurality of partitions is a plurality of throughholes.
A system and method for partitioning a material involves creating a plurality of throughholes in the material to form partitions. These throughholes are arranged to define a network of interconnected channels that facilitate fluid flow or structural reinforcement. The throughholes may be cylindrical, conical, or other shapes and can be distributed uniformly or in a patterned arrangement to optimize performance. The method includes selecting a material, determining the desired throughhole geometry and distribution, and then forming the throughholes using techniques such as drilling, laser cutting, or additive manufacturing. The resulting structure can be used in applications requiring controlled fluid flow, such as filters, heat exchangers, or lightweight structural components. The throughholes may also be filled with a secondary material to enhance properties like thermal conductivity or mechanical strength. The method ensures precise control over the partition geometry and spacing, enabling tailored performance for specific applications.
9. The method of claim 1 , wherein the plurality of partitions is a plurality of droplets.
The invention relates to a method for processing or analyzing samples, particularly in a microfluidic or lab-on-a-chip system. The problem addressed is the efficient and precise manipulation of small sample volumes, such as in biological or chemical assays, where traditional methods may lack accuracy or scalability. The method involves dividing a sample into multiple partitions, which are then individually processed or analyzed. These partitions are specifically implemented as droplets, allowing for precise control over sample volume and isolation. Each droplet can contain a distinct portion of the sample, enabling parallel processing or high-throughput analysis. The use of droplets ensures minimal cross-contamination and allows for precise manipulation of small volumes, which is critical in applications like single-cell analysis, DNA sequencing, or drug screening. The droplets may be generated using microfluidic channels, where the sample is segmented into discrete droplets by an immiscible fluid, such as oil. The droplets can then be transported, merged, or split as needed for the specific application. The method may also include detecting or measuring properties of the droplets, such as their contents or physical characteristics, to extract meaningful data. This approach improves upon prior methods by providing a scalable, high-precision way to handle small sample volumes, reducing errors and increasing throughput in analytical processes. The use of droplets allows for flexible and automated workflows, making it suitable for a wide range of scientific and industrial applications.
10. A system for performing digital polymerase chain reaction (dPCR), the system comprising: a device configured to partition a biological sample volume including a plurality of target nucleic acids into a plurality of partitions, wherein at least one partition includes at least one target nucleic acid; a thermal cycler to amplify the plurality of target nucleic acids; a detector for detecting the number of partitions including at least one target nucleic acid; a memory; and a processor configured to: generate a concentration of target nucleic acids in the biological sample based on a model for volume variation and the number of partitions including at least one target nucleic acid, wherein the model is based on a normal distribution of effective load volume of each of the biological sample volume in the plurality of partitions; and a display to display the concentration of target nucleic acids in the biological sample.
The system performs digital polymerase chain reaction (dPCR) to quantify target nucleic acids in a biological sample. The technology addresses challenges in accurately measuring nucleic acid concentrations due to variability in partition volumes during sample division. The system partitions the sample into multiple compartments, ensuring at least one target nucleic acid is present in some partitions. A thermal cycler amplifies the nucleic acids, and a detector identifies which partitions contain amplified targets. A processor then calculates the concentration of target nucleic acids using a statistical model that accounts for volume variations across partitions, assuming a normal distribution of effective load volumes. The results are displayed for analysis. This approach improves accuracy by compensating for inherent inconsistencies in partition sizes, providing precise quantification of nucleic acids in the sample. The system integrates partitioning, amplification, detection, and computational analysis to deliver reliable concentration measurements.
11. The system of claim 10 , wherein the concentration of target nucleic acids in the biological sample is determined by using the equation: C = v 0 - v 0 2 + 2 σ 2 ln P ( neg ) σ 2 .
This invention relates to a system for quantifying target nucleic acids in a biological sample, addressing challenges in accurate and efficient nucleic acid detection. The system employs a mathematical model to determine the concentration of target nucleic acids based on measured data. The concentration is calculated using the equation C = v0 - (v0^2 + 2σ^2 * ln(P(neg))) / σ^2, where v0 represents an initial measurement value, σ is the standard deviation of the measurement noise, and P(neg) is the probability of a negative result. The system likely includes components for sample processing, nucleic acid detection, and data analysis to derive these parameters. The mathematical model accounts for variability in measurements and noise, improving the accuracy of nucleic acid quantification. This approach is particularly useful in applications requiring precise nucleic acid detection, such as diagnostics, research, or clinical testing. The system may integrate with other nucleic acid analysis techniques, such as PCR or sequencing, to enhance detection sensitivity and reliability. The invention aims to provide a robust method for determining nucleic acid concentrations in diverse biological samples, overcoming limitations of traditional detection methods.
12. The system of claim 10 , wherein the concentration of target nucleic acids in the biological sample is determined by using the equation: P ( neg ) = erfc [ - 1 2 ( v 0 σ - C σ ) ] erfc [ - 1 2 ( v 0 σ ) ] e - Cv 0 + 1 2 σ 2 C 2 .
This invention relates to a system for analyzing biological samples to determine the concentration of target nucleic acids. The system addresses challenges in accurately quantifying nucleic acids in complex biological samples, where background noise and variability can interfere with precise measurement. The system employs statistical methods to enhance detection accuracy by accounting for signal variability and background interference. The system includes a detection mechanism that measures the presence of target nucleic acids in a sample, generating a signal output. The signal output is processed using a statistical model that incorporates the signal variance and a calibration factor to improve measurement precision. The concentration of target nucleic acids is then calculated using a specific equation derived from the error function (erfc), which accounts for the signal distribution and background noise. The equation integrates parameters such as the mean signal (v0), signal standard deviation (σ), and a calibration constant (C) to compute the probability of a negative result (P(neg)), which is inversely related to the target nucleic acid concentration. By applying this equation, the system provides a more reliable quantification of nucleic acid concentration, reducing errors caused by background noise and signal variability. The method is particularly useful in applications requiring high sensitivity and accuracy, such as diagnostic testing and molecular biology research.
13. The system of claim 10 , further comprising: an amplification apparatus configured to amplify the target nucleic acids to determine the number of partitions including at least one target nucleic acid.
This invention relates to a system for analyzing nucleic acids, specifically for quantifying target nucleic acids in a sample by partitioning the sample into multiple compartments and detecting the presence of target nucleic acids in each compartment. The system includes a partitioning apparatus that divides the sample into discrete partitions, such as droplets or chambers, and a detection apparatus that identifies which partitions contain at least one target nucleic acid. The system further includes an amplification apparatus that amplifies the target nucleic acids within the partitions to enhance detection sensitivity and accuracy. By amplifying the target nucleic acids, the system can determine the number of partitions containing at least one target nucleic acid, enabling precise quantification of the target nucleic acids in the original sample. This approach improves the accuracy of nucleic acid detection and quantification by reducing false negatives and increasing the dynamic range of detection. The system is particularly useful in applications such as digital PCR, single-cell analysis, and rare nucleic acid detection.
14. The system of claim 10 , wherein the model for volume variation is: P ( neg ) = erfc [ - 1 2 ( v 0 σ - C σ ) ] erfc [ - 1 2 ( v 0 σ ) ] e - Cv 0 + 1 2 σ 2 C 2 .
This invention relates to a system for modeling volume variation in a physical or financial system, addressing the challenge of accurately predicting changes in volume over time. The system uses a probabilistic model to estimate the likelihood of negative volume variations, incorporating parameters such as initial volume (v0), standard deviation (σ), and a scaling factor (C). The model employs the complementary error function (erfc) to compute the probability of negative volume changes, accounting for both stochastic fluctuations and deterministic trends. The system integrates this model into a broader framework that may include data collection, parameter estimation, and real-time monitoring. The model's mathematical formulation allows for precise quantification of volume variations, enabling applications in risk assessment, resource allocation, or financial forecasting. The invention improves upon prior methods by providing a more accurate and flexible probabilistic framework for volume variation analysis.
16. The system of claim 10 , wherein the plurality of partitions is a plurality of reaction sites.
The invention relates to a system for chemical or biological reactions, specifically addressing the challenge of efficiently managing multiple reaction sites within a single apparatus. The system includes a plurality of partitions, each serving as a distinct reaction site, where individual reactions can occur independently. These partitions are designed to isolate reaction conditions, preventing cross-contamination or interference between different reactions. The system may also incorporate mechanisms for controlling environmental parameters such as temperature, pressure, or reagent delivery to each partition, ensuring precise reaction conditions. Additionally, the partitions may be modular, allowing for easy reconfiguration or scaling of the system to accommodate varying experimental needs. The invention aims to improve reaction efficiency, reproducibility, and throughput by providing a structured, isolated environment for multiple simultaneous reactions. This is particularly useful in fields like drug discovery, synthetic biology, or high-throughput screening, where parallel processing of multiple reactions is essential. The system may also include sensors or monitoring devices to track reaction progress in real-time, further enhancing experimental control and data collection.
17. The system of claim 10 , wherein the plurality of partitions is a plurality of throughholes.
A system for managing fluid flow in a device includes a housing with multiple partitions that divide the interior into separate chambers. These partitions are designed to control the movement of fluid between the chambers, ensuring efficient distribution or separation of the fluid. The partitions are specifically configured as throughholes, which are openings that allow fluid to pass through while maintaining structural integrity. The throughholes can be arranged in a pattern to optimize flow dynamics, such as reducing turbulence or enhancing mixing. The system may also include sensors to monitor fluid properties and actuators to adjust the partitions dynamically, ensuring consistent performance under varying conditions. This design is particularly useful in applications requiring precise fluid control, such as chemical processing, medical devices, or industrial filtration systems. The throughholes provide a balance between fluid permeability and structural support, allowing for customizable flow characteristics based on application needs. The system may further integrate with external controllers to automate adjustments, improving efficiency and reducing manual intervention.
18. The system of claim 10 , wherein the plurality of partitions is a plurality of droplets.
The invention relates to a system for manipulating and analyzing fluid samples, specifically using a plurality of droplets as partitions. The system is designed to address challenges in precise fluid handling, such as minimizing cross-contamination, improving reaction efficiency, and enabling high-throughput analysis. The droplets serve as isolated reaction chambers, allowing for controlled mixing, separation, and detection of substances within each droplet. The system may include mechanisms for generating, transporting, and merging droplets, as well as sensors for monitoring their contents. The use of droplets enhances sensitivity and reduces sample consumption, making the system suitable for applications in biochemistry, pharmaceuticals, and environmental monitoring. The invention may also incorporate techniques for droplet sorting, splitting, or combining based on detected properties, enabling complex workflows in a compact, automated format. The system's modular design allows for customization depending on the specific analytical or processing needs, such as DNA sequencing, protein analysis, or chemical synthesis. The invention improves upon traditional fluid handling methods by providing a scalable, high-precision approach to droplet-based microfluidics.
Unknown
August 20, 2019
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