249 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 present disclosure includes, among other things, methods, kits, and systems for determining the status of lung cancer. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and / or DNA methylation that that are characteristic of the status of lung cancer. In some embodiments, differential modifications and / or differential accessibility are detected and quantified at one or more genomic loci of a biological sample, e.g., in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject with lung cancer. In various embodiments a determined status is useful, e.g., in selecting treatment for and / or treating a lung cancer.

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.

Described herein are gene signatures providing prognostic, diagnostic, treatment and molecular subtype classifications of cancers through genomic and epigenomic profiling, Methods and compositions for determining cancer and subtypes, including breast cancer are described and specific and sensitive detection of biomarkers of interest is provided. Such biomarkers are indicative of disease pathogenesis, which provides opportunity for selection of treatment, including treatment regimes directed at identifying candidates for responsiveness and overcoming resistance mechanisms.

The present disclosure includes, among other things, methods, kits, and systems for determining HER2 status of cancer, e.g., a breast, gastric / gastroesophageal, colorectal, or lung cancer. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and / or DNA methylation that that are characteristic of HER2 status of cancer. In some embodiments, differential modifications and / or differential accessibility are detected and quantified at one or more genomic loci of a biological sample, e.g., in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject with cancer. In various embodiments a determined HER2 status is useful, e.g., in selecting treatment for and / or treating a cancer, e.g., a breast, gastric / gastroesophageal, colorectal, or lung cancer.

The invention relates to the technical field of biology, and discloses a tumor liquid biopsy kit based on a microfluidic technology, the tumor liquid biopsy kit comprises a detection main body, the upper side of the detection main body is provided with a biopsy kit main body, the upper side of the detection main body is provided with a filtering mechanism, and the rear side of the detection main body is provided with a placing mechanism; a heating mechanism is arranged on the inner side of the detection main body, and a plurality of groups of buckling mechanisms are arranged on the right side of the detection main body; the filtering mechanism comprises a stand column, the stand column is arranged on the upper side of the detection body, a plurality of annular grooves are formed in the outer side of the stand column, and four clamping grooves are formed in the lower sides of the annular grooves at equal intervals. Blood impurities and thrombus can be removed through a multi-layer filter by filtering, sample components can be fully mixed by stirring, a reliable result is guaranteed, a reagent bottle placed in a folding manner is convenient to carry, a silica gel cylinder can be stored, and a heating mechanism consists of a controller and a heating pipe, so that the temperature requirement of detection is met, and the process and the result are guaranteed.

The invention discloses a method for detecting a tumor marker PD-L1 by using a composite structure optical fiber sensor based on gold nano sea urchin, which comprises the following steps: preparing a pSC4 solution, and soaking NS-LSPR-FOS in the pSC4 solution for 12 hours; washing to remove uncombined pSC4 molecules; immersing the end face of the sensor in a PBS solution containing 20 [mu] g / mL of PD-L1 antibody for 1 h to form a specific recognition layer; soaking the end face of the sensor in a BSA solution for 20 minutes; the end faces of the sensors are sequentially immersed into PD-L1 antigen solutions with different concentrations, each group is immersed for 45 minutes, and the concentrations are from small to large; and recording a reflection spectrum once every 15 seconds through a spectrograph, tracking resonance valley wavelength movement, and detecting the concentration of PD-L1. Compared with liquid biopsy methods such as ELISA, IFA and a micro-fluidic chip, the liquid biopsy method has the advantages of small size, no mark, real-time detection, in-vivo detection and the like, is expected to overcome two challenges of low concentration and spatial-temporal heterogeneity characterization of tumor marker PD-L1 detection, and plays an important role in cancer research and immunotherapy.

The invention belongs to the field of lung cancer detection, and particularly relates to a platelet marker for detecting lung cancer and a detection kit. The method comprises the following steps: firstly, carrying out transcriptome sequencing on platelets of a healthy (HC) individual and a lung cancer (Lung) individual, then, carrying out differential expression analysis to identify genes which are specifically and differentially expressed in the platelets of a lung cancer patient for the first time, and screening out ZYX, GMPR, RPL9 and RPL11 genes. A logistic regression model is constructed based on mRNA expression levels of the four genes, and in subject working characteristic curve analysis of a training set, the area under a curve is up to 0.97. The application of mRNA expression levels of platelet genes ZYX, GMPR, RPL9 and RPL11 in diagnosis of lung cancer is defined mainly in a liquid biopsy mode, the marker is used for predicting occurrence of the lung cancer, and the invention aims to identify a new marker of the lung cancer and prepare a lung cancer diagnosis kit based on the marker.

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.

The present disclosure includes, among other things, methods, kits, and systems for determining ER status of cancer, e.g., a breast cancer. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and / or DNA methylation that that are characteristic of ER status of cancer. In some embodiments, differential modifications and / or differential accessibility are detected and quantified at one or more genomic loci of a biological sample, e.g., in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject with cancer. In various embodiments a determined ER status is useful, e.g., in selecting treatment for and / or treating a cancer, e.g., a breast cancer.

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.

Systems and methods for molecular residual disease (MRD) status determination for a subject's cancer condition subject uses sequence reads from methylation sequencing of cell-free DNA fragments from the subject's liquid biopsy sample to determine their methylation patterns. From this, corresponding numbers of circulating-tumor DNA (ctDNA) fragments mapping to each of a plurality of regions of the genome of the subject's species are determined. Corresponding expected numbers of noise fragments in each region are determined based on corresponding distributions using observed sequencing depths and learned background emission rates for each region. An excess fragments per million (FPM) value, corrected by an observed CHG methylation level, is determined from the observed number of ctDNA fragments in excess of the expected number of noise fragments in each region. MRD is called when the CHG corrected excess FPM value satisfies a threshold value, and a call against MRD is made when it does not.

The present disclosure encompasses systems, methods, and compositions for diagnosing a subject for a high-grade advanced pre-malignant lesions or colorectal cancer (CRC) disease state by ascertaining the presence of certain one or more glycosylated or aglycosylated peptides in liquid biopsy samples from the subject. Specific embodiments encompass methods of measuring certain one or more glycosylated or aglycosylated peptides in liquid biopsy samples from subjects known to have or suspected of having a high-grade advanced pre-malignant lesions or CRC disease state or subjects undergoing routine health care maintenance for possible presence of a high-grade advanced pre-malignant lesions or CRC disease state. The disclosure provides systems, methods, and compositions to identify subjects at-risk for CRC or high-grade advanced pre-malignant lesions and increases subject colonoscopy compliance, in specific embodiments.

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 provides improved methods for enriching targeted genomic regions of interest to be analyzed by multiplexed parallel sequencing. The methods of the invention utilize a pool of TArget Capture Sequences (TACS), wherein the pool comprises a plurality of TACS families, each member of a family binding to the same target sequence but with different start and / or stop positions on the sequence (i.e., staggered binding of the family members to the target sequence) to thereby enrich for target sequences of interest, followed by massive parallel sequencing and statistical analysis of the enriched population. The methods of the invention can be used for a variety of clinical purposes, including non-invasive prenatal testing for chromosomal abnormalities, for example using a maternal blood sample or a sample of fetal cells, assessment of maternal and paternal carrier status for genetic disorders and detection of tumor biomarkers (e.g., liquid biopsy). Kits for carrying out the methods of the invention are also provided.

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 invention provides a bile sample preservation method. The method comprises the following steps: collecting a bile sample; and mixing the bile sample with a nucleic acid protective agent, and preserving at the temperature of 25-80 DEG C. The invention aims to design a plurality of storage conditions for storing bile from the presence / absence of a bile nucleic acid protective agent, different storage temperature gradients, different storage time periods and the like, and further preliminarily explores the stability of the bile cfDNA, so as to determine the condition for stably storing the bile cfDNA, and provide a foundation for subsequent application of the bile cfDNA to liquid biopsy. And corresponding technical support is provided for the aspects of early clinical diagnosis, prognosis monitoring and the like of patients with malignant biliary tract tumors.

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.