Sample deposit management process
Product Description
The sample library has established a complete inbound and outbound technical process, including transportation, reception, preparation, storage, quality control, transfer, storage, use and destruction, as shown in Figure 5.
(1) Warehousing of samples
Before applying for warehousing, the sample supplier must submit the ethical review approval and the copy of the informed consent signed by the patient/donor; In the sample storage agreement or contract signed between the sample library and the sample supplier, the contents of the sample type, sample quantity, sample information, storage conditions, storage period, sub-packaging information, transportation mode, quality control method, quality control frequency, sample sharing and intellectual property ownership will be specified.
(2) Sample delivery
① For the samples that the sample supplier entrusts the sample library to store on its behalf, when the sample supplier applies for use, the sample supplier shall submit the ex-warehouse application to the sample library, which shall be reviewed by the sample library and signed by the project leader of the sample supplier and the person in charge of the sample library before the ex-warehouse can be arranged.
(1) Warehousing of samples
Before applying for warehousing, the sample supplier must submit the ethical review approval and the copy of the informed consent signed by the patient/donor; In the sample storage agreement or contract signed between the sample library and the sample supplier, the contents of the sample type, sample quantity, sample information, storage conditions, storage period, sub-packaging information, transportation mode, quality control method, quality control frequency, sample sharing and intellectual property ownership will be specified.
(2) Sample delivery
① For the samples that the sample supplier entrusts the sample library to store on its behalf, when the sample supplier applies for use, the sample supplier shall submit the ex-warehouse application to the sample library, which shall be reviewed by the sample library and signed by the project leader of the sample supplier and the person in charge of the sample library before the ex-warehouse can be arranged.
Flow chart of human genetic resources preservation
Preservation types and specifications of natural population samples
Preservation types and specifications of natural population samples
疾病人群样本的保藏类型与规格
② When applying for samples that can be shared by other units/project groups/research groups, and do not involve international cooperation or materials/information exit from the country, it is necessary to submit an ex-warehouse application to the sample library, clarify the project research plan, and submit it to the academic and ethical committee of the sample library; After passing the academic and ethical review, the sample demander, sample supplier and sample library must reach a tripartite agreement on sample utilization; Sample delivery can be arranged after the agreement is signed.
③ When applying for samples that can be shared by other units/project groups/research groups, and involving international cooperation or materials/information exit, the sample demander shall obtain the permission of the Ministry of Science and Technology in accordance with the requirements of the Service Guide for Administrative Licensing Matters for the Examination and Approval of International Cooperative Scientific Research on Human Genetic Resources in China, the Service Guide for Administrative Licensing Matters for the Examination and Approval of Exit of Human Genetic Resources in China and other relevant documents; After obtaining the license, it is required to submit the approval of the administrative license of the Ministry of Science and Technology and the ex-warehouse application to the sample library, clarify the project research plan, and submit it to the academic and ethical committee of the sample library; After passing the academic and ethical review, the sample demander, sample supplier and sample library must reach a tripartite agreement on sample utilization; Sample delivery can be arranged after the agreement is signed.
For the samples in stock, the sample library is responsible for supervision. The sample library shall carry out inventory verification and quality control activities at least once a year. The person in charge of the sample bank is the general person in charge of supervision, and the person in charge of each department and laboratory is the executive body. According to the requirements of the quality management system, the human genetic resources management system is established and improved to ensure the legal use of human genetic resources. For the shared samples used for ex-warehouse use, the ethics committee needs to conduct follow-up review to protect the legitimate rights and interests of patients/donors. All users of shared samples have the obligation to feed back the use of samples to the academic and ethics committee to prevent abuse.
(3) Sample quality control
At the present stage, there are two types of cooperation between sample banks and clinical medical institutions based on sample preservation: one is to jointly establish a pre-treatment laboratory with the hospital to complete sample collection and pre-treatment in the hospital laboratory; The other is to cooperate with the hospital to carry out the natural population cohort study. After the sample collection, the pre-processing link can be completed in the sample database.
In order to realize the quality control of warehousing samples, the key link is the process control. By establishing the standards of personnel training, operation process, reagent consumables, environmental conditions and other relevant elements in the sample collection, transportation, pretreatment and other related links, the sample quality is stabilized, including the following parts:
① Sample information: the corresponding sample tube of the sample must be labeled with the name of the subject (community population), and the label on the sample tube must match the name of the subject on the attachment. The sample information must at least contain the basic information about the subject, the time, place and date of sample collection, the signature of the marked sample corresponding to the subject, the source of the sample, and the relevant clinical information and informed consent (confirmed by signature).
② Requirements for blood sample collection and sub-packaging:
Generally, take the vein in front of elbow or back of hand and vacuum blood sampler to avoid discomfort of participants and loss of sample quality and quantity. The blood samples should be taken from the red cap tube first (the red cap tube does not contain coagulant, and the blood sample volume is 5mL), and then from the purple cap tube (the blood sample volume is 5mL) to avoid cross contamination between additives.
After collection, the blood sample should be temporarily stored at 4 ℃ for no more than 24 hours. The subpackage storage volume of each separated phase is recommended to be less than 2 mL. It is recommended to take 100~250 uL from each tube of serum and plasma, and store them in multiple tubes to avoid repeated freezing and thawing in use and access affecting the sample quality.
Hemolysis and congestion are not considered. Hemolysis can be judged visually and the color can be recognized (from pink to dark red). Avoid the pollution caused by heparin cap in coagulation test; Avoid collecting samples from the place of intravenous infusion (this location is prone to lead to abnormal electrolyte, glucose and drug levels); Before labeling the sample tube to be tested, it is necessary for staff to cross-check the information of participants. Some sample analytes are stable under certain conditions, but some are unstable. Therefore, in order to avoid biological degradation and reduce variables, it is necessary to unify the sample transportation and storage conditions of blood and its separated phase.
③ Urine collection and subpackage requirements:
Generally, 15 mL of the first urine in the morning is collected. For the urine to be analyzed, it is required to centrifuge or transfer it to the urine culture tube containing urine preservative or growth additive as soon as possible for urine analysis or urine bacterial analysis.
The samples should be treated as soon as possible after being collected. Before treatment, the time of placing the samples at 4 ℃ should not exceed 8 hours.
④ Requirements for collection and sub-packaging of fecal samples:
Samples should be taken as soon as possible within 2 hours after the feces are discharged to prevent the excessive growth of aerobic bacteria and facultative anaerobes, which will lead to the deviation of the abundance of bacteria; Prevent the bacterial colony growth inhibition or excessive growth caused by local high temperature from leading to the bias of subsequent analysis results.
⑤ Sample transportation requirements: each sample tube should have an accurate and clear number, and can correspond to the source of the sample one by one; The transported samples shall be packed in leak-proof sealed biohazard plastic bags, and the label paper with sample information mark shall be pasted on the surface of the sample tube, not on the bag; The Warehousing Application/Receipt Form shall be carefully filled out before the samples are put into storage, and shall correspond to the samples one by one; Blood and urine samples are required to be transported at 4 ℃; Fecal samples are required to be transported at - 80 ℃; The samples are sent to the laboratory and RNA extraction is completed within 24h, DNA and protein extraction is completed within 48h, or directly frozen at - 80 ℃ and the sample processing time and storage time are recorded.
⑥ Sampling quality control: the samples after warehousing will be sampled in the year. At present, the quality control process of blood, cell and tissue samples has been developed (see the sample quality control technology flow chart 6 for details).
⑦ Rejection of samples: samples without marks, or with incorrect marks, or failing to meet the relevant requirements for warehousing application (such as sample volume, collection requirements, etc.) will not be warehoused.
③ When applying for samples that can be shared by other units/project groups/research groups, and involving international cooperation or materials/information exit, the sample demander shall obtain the permission of the Ministry of Science and Technology in accordance with the requirements of the Service Guide for Administrative Licensing Matters for the Examination and Approval of International Cooperative Scientific Research on Human Genetic Resources in China, the Service Guide for Administrative Licensing Matters for the Examination and Approval of Exit of Human Genetic Resources in China and other relevant documents; After obtaining the license, it is required to submit the approval of the administrative license of the Ministry of Science and Technology and the ex-warehouse application to the sample library, clarify the project research plan, and submit it to the academic and ethical committee of the sample library; After passing the academic and ethical review, the sample demander, sample supplier and sample library must reach a tripartite agreement on sample utilization; Sample delivery can be arranged after the agreement is signed.
For the samples in stock, the sample library is responsible for supervision. The sample library shall carry out inventory verification and quality control activities at least once a year. The person in charge of the sample bank is the general person in charge of supervision, and the person in charge of each department and laboratory is the executive body. According to the requirements of the quality management system, the human genetic resources management system is established and improved to ensure the legal use of human genetic resources. For the shared samples used for ex-warehouse use, the ethics committee needs to conduct follow-up review to protect the legitimate rights and interests of patients/donors. All users of shared samples have the obligation to feed back the use of samples to the academic and ethics committee to prevent abuse.
(3) Sample quality control
At the present stage, there are two types of cooperation between sample banks and clinical medical institutions based on sample preservation: one is to jointly establish a pre-treatment laboratory with the hospital to complete sample collection and pre-treatment in the hospital laboratory; The other is to cooperate with the hospital to carry out the natural population cohort study. After the sample collection, the pre-processing link can be completed in the sample database.
In order to realize the quality control of warehousing samples, the key link is the process control. By establishing the standards of personnel training, operation process, reagent consumables, environmental conditions and other relevant elements in the sample collection, transportation, pretreatment and other related links, the sample quality is stabilized, including the following parts:
① Sample information: the corresponding sample tube of the sample must be labeled with the name of the subject (community population), and the label on the sample tube must match the name of the subject on the attachment. The sample information must at least contain the basic information about the subject, the time, place and date of sample collection, the signature of the marked sample corresponding to the subject, the source of the sample, and the relevant clinical information and informed consent (confirmed by signature).
② Requirements for blood sample collection and sub-packaging:
Generally, take the vein in front of elbow or back of hand and vacuum blood sampler to avoid discomfort of participants and loss of sample quality and quantity. The blood samples should be taken from the red cap tube first (the red cap tube does not contain coagulant, and the blood sample volume is 5mL), and then from the purple cap tube (the blood sample volume is 5mL) to avoid cross contamination between additives.
After collection, the blood sample should be temporarily stored at 4 ℃ for no more than 24 hours. The subpackage storage volume of each separated phase is recommended to be less than 2 mL. It is recommended to take 100~250 uL from each tube of serum and plasma, and store them in multiple tubes to avoid repeated freezing and thawing in use and access affecting the sample quality.
Hemolysis and congestion are not considered. Hemolysis can be judged visually and the color can be recognized (from pink to dark red). Avoid the pollution caused by heparin cap in coagulation test; Avoid collecting samples from the place of intravenous infusion (this location is prone to lead to abnormal electrolyte, glucose and drug levels); Before labeling the sample tube to be tested, it is necessary for staff to cross-check the information of participants. Some sample analytes are stable under certain conditions, but some are unstable. Therefore, in order to avoid biological degradation and reduce variables, it is necessary to unify the sample transportation and storage conditions of blood and its separated phase.
③ Urine collection and subpackage requirements:
Generally, 15 mL of the first urine in the morning is collected. For the urine to be analyzed, it is required to centrifuge or transfer it to the urine culture tube containing urine preservative or growth additive as soon as possible for urine analysis or urine bacterial analysis.
The samples should be treated as soon as possible after being collected. Before treatment, the time of placing the samples at 4 ℃ should not exceed 8 hours.
④ Requirements for collection and sub-packaging of fecal samples:
Samples should be taken as soon as possible within 2 hours after the feces are discharged to prevent the excessive growth of aerobic bacteria and facultative anaerobes, which will lead to the deviation of the abundance of bacteria; Prevent the bacterial colony growth inhibition or excessive growth caused by local high temperature from leading to the bias of subsequent analysis results.
⑤ Sample transportation requirements: each sample tube should have an accurate and clear number, and can correspond to the source of the sample one by one; The transported samples shall be packed in leak-proof sealed biohazard plastic bags, and the label paper with sample information mark shall be pasted on the surface of the sample tube, not on the bag; The Warehousing Application/Receipt Form shall be carefully filled out before the samples are put into storage, and shall correspond to the samples one by one; Blood and urine samples are required to be transported at 4 ℃; Fecal samples are required to be transported at - 80 ℃; The samples are sent to the laboratory and RNA extraction is completed within 24h, DNA and protein extraction is completed within 48h, or directly frozen at - 80 ℃ and the sample processing time and storage time are recorded.
⑥ Sampling quality control: the samples after warehousing will be sampled in the year. At present, the quality control process of blood, cell and tissue samples has been developed (see the sample quality control technology flow chart 6 for details).
⑦ Rejection of samples: samples without marks, or with incorrect marks, or failing to meet the relevant requirements for warehousing application (such as sample volume, collection requirements, etc.) will not be warehoused.
Flow chart of sample quality control technology
(4) Sample destruction
When the sample has quality problems, or the patient/donor cancels the informed consent, the relevant samples must be destroyed.
Before sample destruction, it must be reviewed and approved by the person in charge of the sample library. When the sample is destroyed, its relevant information and data shall be deleted from the software information system, and the relevant text records shall also be destroyed. Only the copy of the application for revoking the consent provided by the sample supplier and the original record document of the sample destruction shall be retained.
