206 results about "Liquid biopsy" patented technology

The disclosure provides technologies that permit detection and / or characterization of brain biomarkers (e.g., disease-associated biomarkers) in non-CNS samples, including by liquid biopsy (e.g., blood, serum, etc.). Among other things, the present disclosure demonstrates that ultrasound opening of the blood brain barrier can achieve detectable increases in brain-derived materials (e.g., brain-derived proteins, neuron-derived extracellular vesicles, and / or cell-free DNA) in readily-sampled systemic liquids.

The invention relates to a breast cancer plasma transporter miRNA marker and application thereof, and belongs to the technical field of biological detection. In the prior art, biomarkers for breast cancer liquid biopsy have the problems of low content, high heterogeneity, insufficient time resolution and the like, so that the detection reliability is limited. According to the invention, a specific miRNA (micro Ribonucleic Acid) marker (including one or more of let-7d-5p, miR-103a-3p and miR-22-3p) of the plasma transporter is provided. The marker can be used for preparing a breast cancer detection reagent or kit. Clinical verifications show that the miRNAs are remarkably and highly expressed in plasma migrators of breast cancer patients, the AUC value reaches 0.763-0.808, the sensitivity is 66.7%-86.7%, the specificity is 66.7%-88.3%, the miRNAs have the advantages of high signal-to-noise ratio and dynamic monitoring, and the accuracy and practicability of breast cancer detection are remarkably improved.

Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) is determined for each somatic mutation based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the test subject is determined based on the set of VAFs for the one or more somatic mutations.

Systems and methods for determining a blood tumor mutational burden (bTMB) for a test subject are provided in which there is obtained, from a panel-enriched sequencing reaction, a plurality of nucleic acid sequences. The plurality of nucleic acid sequences comprises a corresponding sequence for each cell-free DNA fragment in a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the test subject. Each respective cell-free DNA fragment in the plurality of cell-free DNA fragments corresponds to a respective probe sequence in a plurality of probe sequences used to enrich cell-free DNA fragments in the liquid biopsy sample in the panel-enriched sequencing reaction. There is determined, using the panel-enriched sequencing reaction, that a circulating tumor fraction (ctFE) is above a threshold ctFE value. Responsive to this determination, the bTMB is calculated for the test subject from the panel-enriched sequencing reaction and reported.

The invention provides a non-small cell lung cancer auxiliary diagnosis composition and application and a kit thereof, and relates to the technical field of biological detection.The non-small cell lung cancer auxiliary diagnosis composition comprises a circular RNA ALG8 primer and a circular RNA CAMTA1 primer, circALG8 and circCAMTA1 can be used as markers of early non-small cell lung cancer liquid biopsy, and the non-small cell lung cancer auxiliary diagnosis composition can be applied to diagnosis of non-small cell lung cancer. According to the present invention, with the application of the circALG8 primer and the circCAMTA1 primer, the plasma circALG8 and circCAMTA1 combined diagnosis model can be successfully constructed, the NSCLC patient and the healthy control can be effectively distinguished, the area under the curve is up to 0.8987 when the circALG8 primer and the circCAMTA1 primer are combined to identify the efficiency of the early NSCLC, the identification result has extremely high accuracy, the diagnosis accuracy is significantly improved, the sensitivity reaches 91.78%, and the specificity reaches 75.53%.

The invention discloses a preparation method and application of a photo-thermal biosensor for tumor cell quantification and vitality dual-index liquid biopsy. Phosphatidylserine (PS) is exposed by enriching and cracking tumor cells, is identified and combined by an aptamer Apt2, and is driven to be separated from Apt2-Cu2-xTe NSs; after magnetic separation, separated supernatant is subjected to photo-thermal detection; the photo-thermal signal intensity is positively correlated with the number of cells, so that quantitative detection is realized; during cell apoptosis, PS is turned out of the membrane, Apt2-Cu2-xTe NSs is combined with the surface of the membrane, separated supernatant is subjected to photo-thermal detection after magnetic separation, and the photo-thermal signal enhancement amplitude is in negative correlation with cell activity. The platform has the advantages of POCT characteristics, low cost and portability, and a new tool is provided for precise tumor diagnosis and treatment.

The invention discloses an esophageal adenocarcinoma plasma circulation microbial marker combination, a reagent, a kit, a risk prediction model and application thereof, and belongs to the cross technical field of liquid biopsy and microbiomics. The esophageal adenocarcinoma plasma circulating microbial marker combination disclosed by the invention comprises enterobacteriaceae, cilia, prevotella, ackermania, lactobacillus fermentum and streptococcus. When the esophageal adenocarcinoma plasma circulating microbial marker combination is used for verifying esophageal adenocarcinoma patients and healthy controls, the AUC is 0.952, the sensitivity is 100%, the specificity is 80.00%, the accuracy is 91.43%, the positive predictive value is 86.96%, and the negative predictive value is 100%; the esophageal adenocarcinoma plasma circulating microbial marker combination can effectively distinguish esophageal adenocarcinoma patients from healthy people, is suitable for early screening of esophageal adenocarcinoma, and has remarkable clinical screening application value.

The invention discloses a single cell activity evaluation method based on cell nucleus geometric parameters and a Bayesian framework, which comprises the following steps: establishing a HeLa cell activity gradient model through adriamycin induction, carrying out cell nucleus segmentation by adopting Cell pose 3.0 and extracting 26 geometric features, screening a high-confidence sample in combination with a Bayesian deep learning framework, and evaluating the activity of a single cell according to the high-confidence sample. And constructing a multi-modal feature fusion model to integrate geometric features and deep semantic features, and finally realizing unmarked and high-precision single cell activity evaluation. The method overcomes the limitation that a traditional technology depends on biochemical markers, has the advantages of being easy and convenient to operate, high in flux and high in interpretability, and provides an innovative technical means for tumor liquid biopsy and precise medical treatment.

The application discloses an exosome small non-coding RNA molecule marker and application thereof, and belongs to the field of tumor liquid biopsy and molecular diagnosis. The exosome small non-coding RNA molecule marker is at least one of tRNA-GlyGCC-5 and sRESE; the nucleotide sequence of the tRNA-GlyGCC-5 is shown as SEQ ID NO:1; and the nucleotide sequence of the sRESE is shown as SEQ ID NO:2. The sRESE in the application is a brand new small non-coding RNA sequence, and is first discovered by the inventor, which is important for the marker of esophageal cancer and the research on disease progression mechanism. The tumor diagnosis kit provided by the application, which comprises the exosome small non-coding RNA molecule marker, is a liquid diagnosis monitoring kit with non-invasiveness, high sensitivity, high specificity and applicability to general survey or screening.

A method of identifying a variant as a somatic variant derived from cell free DNA (cfDNA) identifies the variant at a locus based on differences between the nucleic acid sequence for a cfDNA fragment in a plurality of cfDNA fragments and a nucleic acid sequence for the locus in a reference sequence, where the cfDNA fragments are from a liquid biopsy sample from a subject. A set of cfDNA fragments comprising the variant, in the plurality of cfDNA fragments, determines fragment length metrics. A variant allele fraction (VAF) is determined based on comparison of the number of cfDNA fragments having the variant and the total number of cfDNA fragments mapping to the locus. Clonal hematopoiesis prevalence metrics for the variant are obtained. The fragment length metrics, VAF, and hematopoiesis metrics are inputted into a model thereby obtaining, as model output, whether the variant is a somatic variant derived from cfDNA.

Disclosed herein are methods, compositions, and devices for use in diagnosis and treatment of cancer. The methods include sequencing a panel of regions in cell-free nucleic acid molecules and detecting one or more biomarkers that are indicative of a cancer and capability for cancer subtyping.

Among the various aspects of the present disclosure is the provision of a noninvasive and localized brain liquid biopsy using focused ultrasound. Briefly, therefore, the present disclosure is directed to methods and systems to identify brain lesion or tumor characteristics without the need for a solid brain biopsy.

The invention discloses an early-stage lung cancer prediction method based on a multi-modal eccDNA marker, and relates to the technical field of liquid biopsy, and the method comprises the following steps: collecting a peripheral blood sample, carrying out differential centrifugal separation on plasma, constructing a cfDNA library, and carrying out double-end sequencing to obtain original sequencing data; extracting structural features through an eccDNA model, and inputting the structural features into a first machine learning model to generate a circular DNA score; extracting variation features through an SNV model, and inputting the variation features into a second machine learning model to generate a spectrum feature score; extracting copy number features through a CNV model, and inputting the copy number features into a third machine learning model to generate copy number scores; carrying out probability distribution calibration on the circular DNA score, the spectrum feature score and the copy number score; inputting the three types of molecular features into a deep neural network to generate a first fusion score; inputting the calibrated score into a logistic regression model to generate a second fusion score; and generating a final lung cancer risk probability according to the first fusion score and the second fusion score.

Described here are methods to utilize genomic and epigenomic detection platforms to provide quantitative metrics, including those representative of molecular phenotypes, in a variety of iimmuno-oncology applications, including those related to the characterization of patient responsiveness, treatment efficacy, adverse events among otheres. In various embodiments, described herein is an example of generating prognostic and t outcomes of a cfDNA-derived promoter methylation score in predicting ICI benefit.

The invention discloses a postoperative recurrence monitoring system and method for bile liquid biopsy, and relates to the technical field of medical detection, and the method comprises the following steps: obtaining medication data, bile liquid data and gene data of a target object; preprocessing the medication data and the bile liquid data to generate a sampling interference index sequence, and further performing weighted fusion on the gene data by the sampling interference index sequence to obtain a mutation load index of each gene detection time point; and within the time sequence range of the gene data, performing sliding window analysis on the sampling interference index sequence to generate an abnormal chain marker sequence. According to the method, the time sequence mismatch degree is accurately quantified by constructing a time difference matrix, and a weight distribution mechanism is dynamically adjusted in combination with medication volatility, so that the generation process of the sampling interference index can adaptively reflect the influence of medication mode change on the sampling quality; the problem of interference evaluation deviation caused by mismatching of medication data and bile sampling time is effectively solved.

The invention belongs to the technical field of biological medicine, and particularly relates to application of actinomycin D in preparation of a ctDNA detection sensitizer. The invention provides a ctDNA release method based on actinomycin D as an enhancer, which can significantly improve the release level of ctDNA in early small-volume tumors and tiny residual lesions, thereby improving the sensitivity and positive detection rate of liquid biopsy in MRD detection. Under an extremely low dosage, the ActD can generally promote a plurality of human tumor cells to release ctDNA under the condition of not causing obvious cell death, and has good biological safety and adaptability. The method is especially suitable for tiny, biological inert or anatomical position hidden focuses which are difficult to identify by iconography, namely blind area patient groups in disease monitoring, and has a wide clinical application prospect.

The utility model discloses a multifunctional portable liquid biopsy sample collection box which comprises a box body, a lifting handle, an inner cover, a middle cover and an outer cover, the inner cover, the middle cover and the outer cover are all provided with groove structures, fixing devices are arranged in the groove structures, the rear end of the outer cover is hinged to the box body through hinges, and the front end of the outer cover is connected with the box body through groove buckles. Movable rods are connected to the two sides of the middle cover and hinged to the inner wall of the box body, a first temperature control chamber and a second temperature control chamber which are independent are arranged in the box body, the first temperature control chamber is provided with a first inner frame and a first outer frame, and the second temperature control chamber is provided with a second inner frame, a middle frame and a second outer frame; the first inner cover is in mortise and tenon connection with the first inner frame, the second inner cover is in mortise and tenon connection with the middle frame, each corner of the first inner frame and the bottom of the first outer frame corresponding to each corner of the first inner frame are connected with a group of magnetic shockproof devices, and each corner of the middle frame and the bottom of the second outer frame corresponding to each corner of the middle frame are connected with a group of magnetic shockproof devices.

The invention specifically discloses application of VGF as a diagnostic biomarker for prostatic cancer, and relates to the technical field of biological medicines. The secretory protein VGF is identified to be remarkably up-regulated in prostatic fluid of a prostatic cancer patient before puncture for the first time, high expression of the secretory protein VGF is proved to be independently related to shorter progression-free lifetime and total lifetime through a public database, and a brand-new liquid biopsy marker is provided for PCa non-invasive early screening and prognosis evaluation.

The application provides a kind of nanoparticle, preparation method and its early screening related application of cancer, wherein, nanoparticle includes superparamagnetic nanometer core, cationic polymer modified on the surface of superparamagnetic nanometer core and targeted polypeptide grafted on cationic polymer, the targeted polypeptide can specifically recognize tumor specific antigen protein, and has the modular structure of rigid helix and charge repulsion sequence.The plasma low-abundance protein enrichment nanoparticle provided by the application can be used for the detection of early screening of tumor through liquid biopsy, can significantly improve the detection rate of early tumor, and has important clinical significance.

A method and system for diagnosing a subject with respect to a nasopharyngeal carcinoma (NPC) disease state. Peptide structure data corresponding to a biological sample obtained from the subject is received. The peptide structure data is analyzed using a supervised machine learning model to generate a disease indicator that indicates whether biological sample evidences the NPC disease state based on at least 3 peptide structures selected from a group of peptide structures identified in Table 1A and / or 1B. The group of peptide structures in Table 1A and / or 1B comprises a group of peptide structures associated with the NPC disease state. The group of peptide structures is listed in Table 1A and / or 1B with respect to relative significance to the disease indicator. A diagnosis output is generated based on the disease indicator.

The invention provides an EGFR-TKI drug-resistant biomarker detection method based on a non-immobilized GO-SELEX screening aptamer and a kit. In the preparation process of the kit, a nucleic acid aptamer Osi-1 capable of being specifically combined with characteristic protein (Calnexin) in EGFR-TKI drug-resistant cell supernatant is obtained through a GO-SELEX technology. Furthermore, an unmarked optical sensing platform is constructed in combination with gold nanoparticles, so that rapid and sensitive detection of Calnexin is realized. The kit is suitable for early recognition of EGFR-TKI drug resistance, and can be used for clinical liquid biopsy and precise treatment monitoring.

The invention relates to a composition and a kit for detecting tumor-derived tEVs and application of the composition and the kit, and belongs to the technical field of biology. In order to solve the problems of insufficient sensitivity, poor specificity and complex operation of the existing tumor-derived extracellular vesicles (tEVs) detection technology, the invention provides a composition which is composed of double aptamers for specifically recognizing PD-L1 and EpCAM proteins on the surface of the tEVs, a connecting sequence, an annular template, a branch primer, crRNA and a fluorescent probe and is combined with T4DNA ligase, Phi29 polymerase and a CRISPR / Cas12a system. The method is applied to rapid detection of tEVs. Good application prospects are shown in liquid biopsy and dynamic monitoring. Therefore, high-sensitivity and high-specificity tumor tEVs detection is realized, and a reliable tool is provided for early diagnosis of cancers.

The application discloses a free DNA methylation and fragmentomics combined analysis method based on targeted CpG bisulfite sequencing, and belongs to the technical field of liquid biopsy and epigenetic detection. The application extracts cfDNA from blood plasma, carries out high-throughput sequencing after library construction by a methylation adapter, bisulfite conversion, and biotin probe targeted capture of a CpG enrichment region, and simultaneously realizes single-base resolution methylation accurate quantification and FRAGMA fragmentomics analysis by using the same sequencing data, so that the accuracy of methylation quantification results is inferred, and the optimal detection region is iteratively selected; multi-dimensional characteristics such as a methylation ratio, an 11nt cutting map, a CGN / NCG motif ratio and a fragment length distribution are fused to construct a machine learning / deep learning model to output a unified disease risk score. The application realizes the bimodal integration of methylation chemical signals and fragmentomics structural signals in a targeted sequencing system for the first time, and has the advantages of low cost, high sensitivity and strong clinical adaptability.

An imaging structure identification system includes an optical imaging system configured to illuminate a liquid biopsy sample for a subject. The liquid biopsy sample has one or more biological structures that are labeled with one or more fluorophores associated with a fluorescence assay for a disease state allowing detection of emitted electromagnetic radiation from the liquid biopsy sample as image data. The system also includes a processing system configured to identifying the subject as being at reduced risk for having the disease state if the subject profile is similar to the first predetermined profile for subjects not being in the disease state. However, if the subject profile is not similar to the first predetermined profile for subjects not being in the disease state it is not determinative if the subject is in the disease state.

The invention describes a novel nanoparticle coated with a Hypericum perforatum extract and a novel diagnostic kit in which such nanoparticle is used and isolates cancer cells, achieving the effective, accurate and efficient diagnosis and prognosis of different types of cancer, by use of samples from liquid biopsies.

The alimentary canal liquid biopsy sampling device comprises an inner detection part and an outer equipment part, the inner detection part comprises a detection sphere and a spherical shell, the diameter of the detection sphere is smaller than that of the spherical shell, the detection sphere is arranged in an inner cavity of the spherical shell, the spherical shell is hollow, and a magnet part is arranged at one end in the detection sphere; the external equipment part comprises a main body frame, an annular moving part capable of sliding back and forth is arranged on the main body frame, and an electromagnet capable of moving along the inner side wall of the annular moving part is arranged on the inner side of the annular moving part. According to the invention, the internal detection part adopts the detection sphere with the built-in magnetic control and is sleeved with the hollow sphere shell, the detection sphere is isotropic and flexible in steering, the hollow sphere shell rolls during movement, so that the friction force is reduced, the hollow sphere shell is easy to roll in intestinal wrinkles, the rolling speed can be effectively improved, and the magnetic field driving efficiency is effectively improved.

Compositions and methods are provided for determining the presence of early-stage osteoarthritis (OA) in an individual by single cell profiling of a blood sample. Through use of machine learning, it is shown that immune cell features associated with OA are present and detectable in the early stages of OA and can be utilized for early detection of the disease.

The present invention belongs to the field of liquid biopsy, and particularly relates to a method for visualizing the recognition profile of rare single cells, comprising the following steps: specifically staining the cell membranes of circulating tumor cells; adding a fluorescence enhancement reagent, which is an organic phase solution of a surfactant or an organic alcohol; performing microscopic imaging; converting the microscopic image into a digital photograph, and amplifying the digital signal in the digital photograph to obtain a visualized cell contour map. The present invention uses a surfactant or an organic alcohol to enhance the specific fluorescence on the cell surface, thereby improving the signal-to-noise ratio of the surface fluorescence signal; by using digital signal amplification technology, the visualization of the specific recognition profile of single cells is achieved, avoiding signal loss of the imaged cells; based on the fluorescence-visualized cell contour, the accuracy of capturing CTC counting and size estimation can be realized.

To provide methods and systems for tumor informed circulating tumor fraction estimation.SOLUTION: Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) for each somatic mutation is determined based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the subject is determined based on the set of VAFs for the one or more somatic mutations.SELECTED DRAWING: Figure 1A

A method for analysing chromosome interactions relating to canine cancer wherein the chromosome interactions relate to either a class of cancer or a specific cancer. The invention allows use of a liquid biopsy method.