阅读说明：本技术 一种生物试样分析系统 (biological sample analysis system ) 是由 庞莹莹 赵东旭 于 2019-11-23 设计创作，主要内容包括：一种生物试样分析系统,试样流路上的生物分子通过平行电极时,导致平行电极之间的隧道电流变化,根据电流变化来判断分析信号；其中,在试样流路上设置第一电极对以及第二电极对,在第一电极对以及第二电极对之间分别设置具有相反极性的电化学活性分子,根据试样通过第一电极对时第一电极对的第一电流变化量和/或通过第二电极对时第二电极对的第二电流变化量,确定试样参数。本发明的生物试样分析系统能够用于核酸、氨基酸、蛋白质、花粉、病毒、细胞、有机粒子或无机粒子等的检测,提高检测的灵敏度,更加精确地确定生物试样的参数。(A biological sample analysis system, wherein a electrode pair and a second electrode pair are provided in a sample flow path, electrochemically active molecules having opposite polarities are provided between a electrode pair and the second electrode pair, respectively, and sample parameters are determined based on a current variation of the electrode pair when the sample passes through the electrode pair and/or a second current variation of the second electrode pair when the sample passes through the second electrode pair.)

A biological sample analysis system of the type 1 and , comprising a sample flow path in which a th electrode pair and a second electrode pair are provided, wherein the current direction of the th electrode pair is perpendicular to the sample flow direction, the current direction of the second electrode pair is perpendicular to the sample flow direction, a th solution containing th electrochemically active molecules is disposed in a moving path between the th electrode pair, a second solution containing second electrochemically active molecules is disposed in a moving path between the second electrode pair, the th electrochemically active molecules and the second electrochemically active molecules are electrochemically active particles having different types of charges, and a signal analyzer for determining the volume and the charge amount of the sample based on the th current variation of the th electrode pair when the sample passes through the th electrode pair and/or the second current variation of the second electrode pair when the sample passes through the second electrode pair.

2. The biological sample analysis system according to claim 1, wherein the th electrochemically active molecule is an electrochemically active molecule capable of undergoing a redox reaction on the th electrode pair, and the second electrochemically active molecule is an electrochemically active molecule capable of undergoing a redox reaction on the second electrode pair.

3. The biological sample analysis system of claim 2, wherein: the biological sample analysis system is used for analyzing biological samples such as cells, viruses, proteins and the like.

4. The biological sample analysis system according to claim 3, wherein the th electrode pair and the second electrode pair are arranged along the same sample flow path.

5. The system for analyzing a biological sample according to claim 4, wherein the concentration of electrochemically active molecules in the th solution is the same as the concentration of second electrochemically active molecules in the second solution.

6. The system according to claim 5, wherein the th electrode pair has a length equal to that of the second electrode pair, and the th electrode pair has a distance equal to that of the second electrode pair.

7. The system according to claim 6, wherein the th and second current variations are generated when the same sample passes between the th and second electrode pairs, respectively.

8. The system for analyzing a biological sample according to claim 7, wherein the th current variation is an average value of current variation values generated by the sample between the th electrode pair in a specific time, and the second current variation is an average value of current variation values generated by the sample between the second electrode pair in a specific time.

9. The biological sample analysis system of claim 8, wherein: the device further comprises a correlation storage unit for storing the correlation between the standard sample and the current variation value.

10. The biological sample analysis system according to claim 9, wherein the correlation stored in the correlation storage unit includes a correlation between a change in current when the standard neutral sample passes through the th solution and a volume of the standard neutral sample, a correlation between a change in current when the standard neutral sample passes through the second solution and a volume of the standard neutral sample, a correlation between a change in current when the sample having an electrical property identical to that of the th electrochemically active molecule, a change in current when the sample having a different standard volume and a different standard charge amount passes through the th solution, and a correlation between a change in current when the sample having an electrical property identical to that of the second electrochemically active molecule, a change in current when the sample having a different standard volume and a different standard charge amount passes through the second solution, and a charge amount and a volume.

Technical Field

The present invention relates to an analysis system for measuring a test electrochemical variable, and more particularly, to a biological sample analysis system for analyzing a biological sample by measuring an electrochemical variable.

Background

The electrochemical analysis method is a -class analysis method established based on the relationship between the composition and content of the analyzed solution and its electrochemical properties in an electrolytic cell by using the basic principle and experimental technique of electrochemistry, and is generally to make the sample solution to be analyzed form an electrolytic cell, and then convert the concentration of the sample to be measured into electrical parameters for measurement according to the relationship between some measured electrical parameters (such as current, potential difference, resistance, etc.) of the formed cell and the physical or chemical properties of the substance to be measured.

In order to solve the above problems, the invention of CN104583767B provides improved techniques, which can amplify the signal of the sample when passing through the electrode pair by disposing a solution of electrochemically active molecules that undergo redox reaction on the electrode pair between the electrode pair, thereby increasing the baseline current between the electrode pair, and thus amplifying the signal of the sample when passing through the electrode pair, thereby increasing the sensitivity of detection.

However, the resulting change in the specimen across the pair of electrodes includes a specimen volume-induced current change and a specimen charge-induced current change, which for a neutral specimen can be determined by a standard volume of specimen to current change curve or table, from which the specimen volume can be determined; however, for the charged sample whose volume and charge are unknown, the current change due to the volume and the current change due to the sample charge cannot be determined in the prior art, and in the CN104583767B, when the volume and charge of the charged sample are calculated, the volume of the charged sample can be determined only by using the total current change value of the charged sample as the current change value due to the volume, and the charge of the charged sample can be determined by using the total current change value of the charged sample as the current change value due to the sample charge, which results in inaccurate calculation.

Disclosure of Invention

The present invention provides, as an improvement of CN104583767B, biological sample analysis systems, which can determine the charge-induced tunnel current variation and the volume-induced tunnel current variation when a charged sample with unknown volume and charge passes through parallel electrodes, thereby more accurately determining the parameters of the biological sample.

according to the present invention, there are provided biological sample analysis systems including a sample channel in which a first 0 electrode pair and a second electrode pair are provided, wherein a current direction of the first electrode pair is perpendicular to a sample flow direction, a current direction of the second electrode pair is perpendicular to the sample flow direction, a th solution containing a th electrochemically active molecule is disposed in a movement path between the first electrode pair, a second solution containing a second electrochemically active molecule is disposed in a movement path between the second electrode pair, the first th and second electrochemically active molecules are electrochemically active particles having different kinds of charges, and a signal analyzer determining a volume and a charge amount of the sample based on a current change amount of the sample at a th electrode pair of a electrode pair and electrode pair and/or a current change amount of the sample at the second electrode pair.

, the th electrochemically active molecule is an electrochemically active molecule capable of undergoing a redox reaction on the th electrode pair, and the second electrochemically active molecule is an electrochemically active molecule capable of undergoing a redox reaction on the second electrode pair.

, the biological sample analysis system is used for analyzing biological samples such as cells, viruses, proteins, etc.

, the test sample of the biological sample analysis system is the same attribute sample.

Further , the electrode pair and the second electrode pair are disposed along the same sample flow path.

, the concentration of the th electrochemically active molecule in the solution is the same as the concentration of the second electrochemically active molecule in the second solution.

, the length of the electrode pair is equal to the length of the second electrode pair, and the distance between the electrode pair is equal to the distance between the second electrode pair.

Further , the current variation and the second current variation are generated when the same sample passes through the electrode pair and the second electrode pair, respectively.

, the th current variation is an average value of current variation values generated by the plurality of samples passing through the th electrode pair in a specific time, and the second current variation is an average value of current variation values generated by the plurality of samples passing through the second electrode pair.

Further , setting the voltage between the electrode pair to be th voltage, the voltage between the second electrode pair to be second voltage, the th voltage and the second voltage making the reference current when no sample passes between the th electrode pair equal to the reference current when no sample passes between the second electrode pair.

The step further includes a correlation storage unit that stores a correlation between the standard sample and the current change value.

, the correlation relationships stored in the correlation relationship storage unit include a correlation between a current change amount of the standard neutral sample when the standard neutral sample passes through the th solution and a volume of the standard neutral sample, a correlation between a current change amount of the standard neutral sample when the standard neutral sample passes through the second solution and a volume of the standard neutral sample, a correlation between a current change amount of the sample having an identical electrical property to the th electrochemically active molecule, a correlation between a current change amount of the sample having a different standard volume and a different standard charge amount when the sample having an identical electrical property to the th solution, a correlation between a current change amount of the sample having an identical electrical property to the second electrochemically active molecule, a correlation between a current change amount of the sample having a different standard volume and a different standard

, the signal analysis unit determines the volume and the charge amount of the sample according to the correlation stored in the correlation storage unit and the th current variation of the sample passing through the th electrode pair, the th electrode pair and the second current variation of the sample passing through the second electrode pair.

Step , the signal analysis portion determines the volume V and the charge Q of the sample according to the following steps, 1, judging whether the sample is charged or not, if the sample is not charged, the step 2 is performed, if the sample is charged, the step 3 is performed, 2, calculating the volume V of the sample according to the th current variation and the correlation between the current variation and the volume of the standard neutral sample passing through the th solution stored in the storage portion, and ending the analysis, 3, calculating X = (A-B)/2, Y = (A + B)/2, wherein X represents the amount of current variation caused by the charge of the sample in the solution electrically identical to the sample, X represents the amount of current variation caused by the charge of the sample in the solution electrically different from the sample, Y represents the amount of current variation caused by the volume of the sample, A is the amount of current variation with the larger absolute value of the current variation of the th sample and the second current variation, B is the amount of current variation of the second sample 539, and the amount of current variation caused by the sample, and the volume of the sample is calculated based on the correlation between the current variation and the volume of the standard neutral sample, and the volume of the sample, and the correlation between the stored in the sample, and the volume of the stored values of the sample, and the stored values of the standard neutral sample, and the correlation of the stored values of the stored in the stored volume of the stored in the stored solution, and the stored values of the stored in the stored volume.

And , calculating the absolute value of the difference between the th current variation and the second current variation, if the absolute value is less than the threshold, judging that the sample is not charged, and if the absolute value is greater than the threshold, judging that the sample is charged.

In the step (5), in the step , the column closest to the V value is selected from the correlation table of the solutions corresponding to the a values, and the Q value corresponding to the X value in the column is determined by fitting, and is the Q value of the charge of the sample.

Optionally, in the step (5), from the correlation table of the solution corresponding to the value a, a V1 value column and a V2 value column which are closest to the value V are selected, and a corresponding value Q1 of the value X in the V1 value column and a corresponding value Q2 in the V2 value column are determined by fitting; the sample charge Q value was calculated from (Q-Q1)/(V-V1) = (Q2-Q1)/(V2-V1).

Detailed Description

In order to more clearly illustrate the technical solutions of the present invention, the present invention will be briefly described below by using embodiments, and it is obvious that the following description is only embodiments of the present invention, and it is obvious for those skilled in the art to obtain other technical solutions according to these embodiments without inventive labor, and also fall into the disclosure of the present invention.

The biological sample analysis system according to an embodiment of the present invention is a biological sample analysis system for detecting a biological sample, and a detection target of the biological sample may be a conventional sample including nucleic acid (DNA or RNA), amino acid, protein, pollen, virus, cells, organic particles, inorganic particles, or the like.

A th electrode pair and the second electrode pair are provided along the same sample flow path, the length of the th electrode pair is equal to the length of the second electrode pair, the distance between the th electrode pair is equal to the distance between the second electrode pair, the current direction of the th electrode pair is perpendicular to the sample flow direction, the current direction of the second electrode pair is perpendicular to the sample flow direction, a 5 th solution containing a th electrochemically active molecule is disposed in a moving path between the th electrode pair, a second solution containing a second electrochemically active molecule is disposed in a moving path between the second electrode pair, a th electrochemically active molecule and the second electrochemically active molecule are electrochemically active particles having different kinds of charges, for example, a th electrochemically active molecule is an electrochemically active molecule having a positive charge that is capable of undergoing a redox reaction on the second electrode pair, a second electrochemically active molecule having a negative charge that is capable of undergoing a redox reaction on the second electrode pair, a second electrode pair is disposed between a positive charge concentration of the electrochemically active molecule in the second electrochemically active molecule that is capable of undergoing a redox reaction on the second electrode pair, a voltage of no current is equal to the second reference voltage , and a reference voltage is not applied between the second electrode pair when a reference voltage is equal to the second electrode pair, no current is applied between the second electrode pair, no reference voltage, no reference.

, the correlation relationship stored in the correlation relationship storage unit includes the correlation relationship between the current change when the standard neutral sample passes through the th solution and the volume of the standard neutral sample, the correlation relationship between the current change when the standard neutral sample passes through the second solution and the volume of the standard neutral sample, the correlation relationship between the current change when the standard neutral sample passes through the th solution and the charge amount and the volume of the sample with the same electric property as the th electrochemically active molecule, the correlation relationship between the current change when the different standard volumes and the different standard charge amount samples pass through the second solution and the correlation relationship between the charge amount and the volume of the sample with the same electric property as the second electrochemically active molecule and the current change when the different standard volumes and the different standard charge amount samples pass through the second solution.

The sample is a -identical attribute sample, the th and second current changes may be generated between th and second electrode pairs respectively from a sample, or may be an average of current changes generated between th electrode pairs from a plurality of samples, when the latter is used, the average of current changes between th electrode pairs within a specific time period is selected as a th current change, the time for the sample to pass through the second electrode pair within the specific time period is determined according to the flow speed of the sample in the sample flow path, and the average of current changes between the second electrode pairs within the time period is selected as the second current change.

The signal analysis section determines the volume and the charge amount of the sample based on the correlation stored in the correlation storage section and the th current variation of the th electrode pair when the sample passes through the th electrode pair and the second current variation of the second electrode pair when the sample passes through the second electrode pair;

(1) calculating the absolute value of the difference between the th current variation and the second current variation, if the absolute value is less than the threshold, judging that the sample does not have the sample, entering the step (2), if the absolute value is more than the threshold, judging that the sample has the charge, and carrying out the step (3), wherein the threshold can be determined according to the precision of the current sensor;

(2) calculating a sample volume V through the current variation and the correlation between the current variation and the volume of the standard neutral sample passing through the solution stored in the storage unit, or calculating the volume V of the sample through the second current variation and the correlation between the current variation and the volume of the standard neutral sample passing through the second solution stored in the storage unit;

(3) calculating X = (A-B)/2, Y = (A + B)/2, wherein X represents the current change caused by the sample charge in the solution with the same electrical property as the sample charge, X represents the current change caused by the sample charge in the solution with the different electrical property as the sample charge, Y represents the current change caused by the sample volume, A is the current change with the large absolute value in the th current change and the second current change, and B is the current change with the small absolute value in the th current change and the second current change;

(4) calculating a sample volume V based on the correlation between the Y value and the volume and the current change value of the standard neutral sample passing through the solution corresponding to the A value stored in the storage unit;

(5) in step (5), from the correlation table of the solution corresponding to the value A, a column closest to the value V is selected, and the value Q corresponding to the column X is determined by interpolation, and the value Q of the sample charge is obtained, and from the correlation table of the solution corresponding to the value A, a column V1 and a column V2 closest to the value V are selected, and the corresponding value Q1 of the value X in the column V1 and the corresponding value Q2 in the column V2 are determined by fitting, and the value Q of the sample is obtained from (Q-Q1)/(V-V1) = (Q2-Q1)/(V2-V1).

Further, it is to be understood that after reading the above disclosure of the present invention, the scope of the present invention is not limited to the above embodiments, and that various changes or modifications may be made by those skilled in the art without departing from the principle of the present invention, which is also defined in the scope of the appended claims.