CN108088985A - Biological monitor and biological detecting method - Google Patents
Biological monitor and biological detecting method Download PDFInfo
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- CN108088985A CN108088985A CN201710680777.0A CN201710680777A CN108088985A CN 108088985 A CN108088985 A CN 108088985A CN 201710680777 A CN201710680777 A CN 201710680777A CN 108088985 A CN108088985 A CN 108088985A
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- biological
- detection chip
- biological detection
- electrical parameter
- initial value
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/4875—Details of handling test elements, e.g. dispensing or storage, not specific to a particular test method
Abstract
The present invention proposes a kind of biological monitor and biological detecting method.Biological detecting method includes：In no added biological respinse solution, the initial value of biological detection chip is corrected in advance；In biological detection chip, only first add in biological respinse solution but be added without sample survey, also, measure interelectrode first electrical parameter possessed by biological detection chip；In biological detection chip, while biological respinse solution and sample survey are added in, also, measure interelectrode second electrical parameter possessed by biological detection chip；Compare the difference between the second electrical parameter and the first electrical parameter, determine whether there is the presence for the biomolecule to be detected accordingly.
Description
Technical field
The present invention relates to a kind of biological monitor and biological detecting method, adaptable detection correction mechanism, energy
It is enough to be widely used for detecting differential responses solution and different biological targets.
Background technology
It please refers to Fig.1, shows the step flow chart of the biological detecting method of the prior art.As shown in Figure 1, this existing skill
Art is firstly added deionized water in biological detection chip, thus measures electrical parameter between two parallel poles (such as：Impedance value
Or capacitance) (the step S11 for referring to Fig. 1).Then, in step s 12, remove deionized water (the above step for before reaction,
Purpose is to confirm initial value).
Then, in step s 13, in biological detection chip, sample survey and reaction reagent are added in, performs biological respinse
(the above step in reaction).
Followed by, it is necessary to remove the reaction reagent that is added in step s 13 in step S14a.Followed by step
, it is necessary to add in deionized water once again in biological detection chip in S14b.Then, two can be measured once again in step S14c
Electrical parameter between parallel pole is (such as：Impedance value or capacitance).
Finally, comparison step S14c and the electrical parameters of step S11 therebetween be (such as：Impedance value or capacitance) difference
It is different, that is, compare initial value and the numerical value after reaction, the presence for the biomolecule to be detected is determined whether there is accordingly.
The biological detecting method of this prior art has the shortcomings that following：(1) since deionized water will add in and wash away, compared with
For trouble.(2) furthermore, the step of " the removal reaction reagent " of step S14a, can take away partial reaction object, and this can be seriously affected
Interpretation, the measurement for causing the biological detecting method of the prior art are inaccurate.
US publication case US 2004/0110277 and US 2013/ are seen with the relevant patent of the application
0143775 etc..
In view of this, the present invention proposes a kind of biological monitor and biological detecting method, adaptable detection school
Positive mechanism can be widely used for detecting differential responses solution and different biological targets.
The content of the invention
It is an object of the invention to overcome the deficiencies in the prior art and defect, propose a kind of biological monitor and biology
Detection method, adaptable detection correction mechanism can be widely used for detecting differential responses solution and different biology marks
's.
For achieving the above object, just a wherein viewpoint is sayed, the present invention provides a kind of biological detecting method, comprising：
(A) in no added one biological reaction solution, an initial value of a biological detection chip is corrected in advance；(B) in the biological detection
In chip, only first add in the biological respinse solution but be added without a sample survey, also, measure the biological detection chip to be had
Interelectrode one first electrical parameter；(C) in the biological detection chip, while the biological respinse solution and the inspection are added in
Sample, also, measure interelectrode one second electrical parameter possessed by the biological detection chip；And (D) comparison step (C)
Second electrical parameter and step (B) first electrical parameter between difference, determine whether there is the life to be detected accordingly
The presence of object molecule.
In a kind of preferably implementation kenel, which includes：(A1) starting of the biological detection chip is exported
Value；(A2) judge the initial value whether between a relevant range；(A3) when the initial value is between the relevant range, carrying out this should
Step (B)；And (A4) is corrected within the initial value to the relevant range when the initial value is not between the relevant range.
In above-mentioned preferable implementation kenel, which further includes：(A0) before the step (A1), input one is driven
Signal is moved to the biological detection chip.
In a kind of preferably implementation kenel, which includes：(B1) the output phase on first electrical parameter one
First output signal；(B2) judge whether the first output signal reaches a basic level；(B3) when the first output signal is
Reach the basic level, carry out the step (C)；And (B4) when this first output signal be not reaching to the basic level, adjust
The level of the whole first output signal is to the basic level.
In above-mentioned preferable implementation kenel, which further includes：(B0) before the step (B1), input one is driven
Signal is moved to the biological detection chip.
In a kind of preferably implementation kenel, which includes：(C1) the output phase on second electrical parameter one
Second output signal.
In above-mentioned preferable implementation kenel, which further includes：(C0) before the step (C1), input one is driven
Signal is moved to the biological detection chip.
In a kind of preferably implementation kenel, which includes a buffer solution or an electrolyte.
In a kind of preferably implementation kenel, first electrical parameter and second electrical parameter include an impedance value respectively
An or capacitance.
Another viewpoint is sayed, the present invention provides a kind of biological monitor, comprising：An at least biological detection chip is used
To contain a biological reaction solution and/or a sample survey；One detection circuit, to export a starting of the biological detection chip
Value and/or a measuring signal, wherein, which includes：One first electrical parameter, be in the biological detection chip,
When only first adding in the biological respinse solution but being added without the sample survey, for institute between electrode possessed by the biological detection chip
The measuring signal of measurement；And/or one second electrical parameter, it is in the biological detection chip, while adds in the biology instead
When answering solution with the sample survey, for the measuring signal measured between electrode possessed by the biological detection chip；One control
Circuit processed, to judge that the initial value of the biological detection chip whether between a relevant range or according to the measuring signal, is sentenced
Whether the disconnected one first output signal for being relevant to first electrical parameter reaches a basic level；One correcting circuit, to basis
The judging result of the control circuit in no added one biological reaction solution to biological detection chip, corrects the starting in advance
Within value to the relevant range；And an adjustment circuit, to the judging result according to the control circuit, adjust first output
The level of signal is to the basic level.
In a kind of preferably implementation kenel, the biological monitor further includes a multiplexer, to multitask
Multiple biological detection chips are controlled, wherein the plurality of biological detection chip is with the matrix arrangement of 1x N.
In a kind of preferably implementation kenel, the biological monitor further includes at least two multiplexers, to more
The multiple biological detection chips of task control, wherein the plurality of biological detection chip is with the matrix arrangement of N x N.
Preferably implement kenel a kind of, the biological detection chip be it is multiple, and the plurality of biological detection chip with
Arranged in series.
Preferably implement kenel a kind of, the biological detection chip be it is multiple, and the plurality of biological detection chip with
It is arranged in parallel.
In a kind of preferably implementation kenel, which includes a buffer solution or an electrolyte.
In a kind of preferably implementation kenel, first electrical parameter and second electrical parameter include an impedance value respectively
An or capacitance.
Another viewpoint is sayed, the present invention provides a kind of biological monitor, comprising：One control biological detection chip, is used
To contain a biological reaction solution；An at least biological detection chip, to contain a biological reaction solution and/or an inspection sample
Product；One detection circuit, to export the 1 of one first initial value of the control biological detection chip or the biological detection chip
Two initial values and to compare the 1 of one first measuring signal of the control biological detection chip and the biological detection chip
Difference between two measuring signals；Wherein, which includes：One first electrical parameter is in control biology
In detection chip, when only first adding in the biological respinse solution but being added without the sample survey, for the control biological detection chip
Measured first measuring signal between possessed electrode；Wherein, which includes：One second electrical parameter,
It is in the biological detection chip, while when adding in the biological respinse solution and the sample survey, for the biological detection core
Measured second measuring signal between electrode possessed by piece；One control circuit, to judge the control biological detection chip
First initial value or the biological detection chip second initial value whether between a relevant range or according to the measurement believe
Number, judge whether the one first output signal for being relevant to first electrical parameter reaches a basic level；One correcting circuit, to
According to the judging result of the control circuit, examined in no added biological respinse solution to the control biological detection chip or the biology
When surveying chip, correct in advance respectively within first initial value or second initial value to the relevant range；And one adjustment electricity
Road to the judging result according to the control circuit, adjusts the level of the first output signal to the basic level.
In a kind of preferably implementation kenel, which includes a buffer solution or an electrolyte.
In a kind of preferably implementation kenel, first electrical parameter and second electrical parameter include an impedance value respectively
An or capacitance.
Another viewpoint is sayed, the present invention provides a kind of biological monitor, comprising：One control biological detection chip, is used
To contain a biological reaction solution；An at least biological detection chip, to contain a biological reaction solution and/or an inspection sample
Product；One detection circuit, to export the 1 of one first initial value of the control biological detection chip or the biological detection chip
Two initial values and to compare the 1 of one first measuring signal of the control biological detection chip and the biological detection chip
Difference between two measuring signals；Wherein, which includes：One first electrical parameter is in control biology
In detection chip, when only first adding in the biological respinse solution but being added without the sample survey, for the control biological detection chip
Measured first measuring signal between possessed electrode；Wherein, which includes：One second electrical parameter,
It is in the biological detection chip, while when adding in the biological respinse solution and the sample survey, for the biological detection core
Measured second measuring signal between electrode possessed by piece；One control circuit, to judge the control biological detection chip
First initial value or the biological detection chip second initial value whether between a relevant range or according to the measurement believe
Number, judge whether the one first output signal for being relevant to first electrical parameter reaches a basic level；One correcting circuit, to
According to the judging result of the control circuit, examined in no added biological respinse solution to the control biological detection chip or the biology
When surveying chip, correct in advance respectively within first initial value or second initial value to the relevant range；And one adjustment electricity
Road to the judging result according to the control circuit, adjusts the level of the first output signal to the basic level.
In a kind of preferably implementation kenel, the biological monitor further includes a multiplexer, to multitask
The control biological detection chip and multiple biological detection chips are controlled, wherein the control biological detection chip and the plurality of biology inspection
Chip is surveyed with the matrix arrangement of 1x N.
In a kind of preferably implementation kenel, the biological monitor further includes at least two multiplexers, to more
The task control control biological detection chip and multiple biological detection chips, wherein the control biological detection chip and the plurality of life
Analyte detection chip is with the matrix arrangement of N x N.
Below by way of specific embodiment elaborate, should be easier to understand the purpose of the present invention, technology contents, feature and
The effect of it is realized.
Description of the drawings
Fig. 1 shows the step flow chart of the biological detecting method of the prior art；
Fig. 2 shows the step flow chart of the first embodiment of the biological detecting method of the present invention；
Fig. 3 shows the more specific embodiment of the step flow chart of Fig. 2；
Fig. 4 is shown, corresponding to Fig. 2~Fig. 3, the block schematic diagram of the first embodiment of biological monitor of the invention；
Fig. 5 shows the step flow chart of the second embodiment of the biological detecting method of the present invention；
Fig. 6 is shown, corresponding to Fig. 5, the block schematic diagram of the second embodiment of biological monitor of the invention；
Fig. 7 marks the 3rd embodiment of the biological monitor of the present invention；
Fig. 8 marks the fourth embodiment of the biological monitor of the present invention；
Fig. 9 marks the 5th embodiment of the biological monitor of the present invention；
Figure 10 marks the sixth embodiment of the biological monitor of the present invention.
Specific embodiment
It is related to foregoing and other technology contents, feature and effect of the present invention, one in following cooperation attached drawing preferably implements
In the detailed description of example, can clearly it present.Attached drawing in the present invention belongs to signal, be mostly intended to represent fabrication steps and
Orbution up and down between each layer then and not according to ratio is drawn as shape, thickness and width.
Please refer to Fig.2-3 and compares figure 4.Fig. 2 shows that the step of first embodiment of the biological detecting method of the present invention flows
Cheng Tu.Fig. 3 shows the more specific embodiment of the step flow chart of Fig. 2.Fig. 4 is shown, corresponding to Fig. 2~Fig. 3, biology of the invention
The block schematic diagram of the first embodiment of detection device.
As shown in figure 4, biological monitor 20 includes a biological detection chip 21, a detection circuit 22, a control circuit
23rd, a correcting circuit 24 and an adjustment circuit 26.In addition, biological monitor 20 is selectively included an Analog-digital Converter
Circuit (ADC) 25.Biological monitor 20 in the present embodiment, it is illustrated that is only that citing includes a biological detection chip
21.In other embodiments, biological detection chip 21 can be multiple not limit only comprising a biological detection chip 21.
In one embodiment, biological detection chip 21 can utilize the hollow structure in encapsulation to contain place as sampling appearance liquid.
The present embodiment is put unlike the prior art to be：As shown in Fig. 2, biological respinse solution is not yet being added (depending on needed for
Such as, but not limited to can be buffer solution or electrolyte depending on the biological detection purpose to be carried out) when, first correction biology inspection
Survey the initial value of chip 21 (refering to the step S214 of the step S21 and Fig. 3 of Fig. 2).Then, Fig. 3, display biology be please refer to
How detection device 20 corrects the initial value of biological detection chip 21 in advance.As shown in figure 3, biological monitor 20 can pass through tune
Whole circuit 26 inputs a drive signal SE to biological detection chip 21 (the step S211 for referring to Fig. 3).Then, biological detection chip
21 initial value can be exported (the step S212 for referring to Fig. 3) by detection circuit 22.Wherein, so-called " initial value " can be
The electrical parameter between two parallel poles in biological detection chip 21 is measured, and this electrical parameter such as, but not limited to can be electricity
Capacitance or impedance value.
In biological detection, biomolecule, with known reagent reacting, can produce in the encapsulation of exposed Bio-Cell condenser types
The variation of raw two kinds of capacitances, a capacitance for being biomolecule and being fixed on the induction electrode surface after the receptor response of electrode
Change (Cbio), the other is the capacitance (C between two parallel polesgap), summation and available following relational expressions expressions：
Wherein, CtotFor total capacitance value, A represents electrode area, and t represents the spacing between electrode, and ε represents to delay between electrode
Rush the dielectric constant of solution or electrolyte.Moreover, reaction can influence capacitance, impedance value can be also influenced, accordingly it is also possible to survey
Amount impedance value judges to be detected.
It is worth noting that, the drive signal SE of the step S211 of Fig. 3 must be not necessarily inputted to biological detection chip 21, this
Only selective step (therefore the step S211 of Fig. 3 is illustrated with dashed rectangle).It is, some biological detections are directed to,
Drive signal SE can not be applied and directly read initial value.On the other hand, in the present embodiment, then preferably it is arranged to：Make
It adjusts to the being adapted to property of drive signal SE applied, i.e. can drive signal be adjusted according to the characteristic of different determinands
Initial value is adaptively set in relevant range by SE.Such as some determinands, capacitance reactions change may
In some order of magnitude, and for other some determinands, capacitance reactions change may be in another order of magnitude, between the two
It may be poor hundred times.Or during for the progress biological detection reaction of some determinands, the buffer solution or electrolyte that use can be made
It is reacted into more sensitive capacitance, and for buffer solution when in addition some determinands carry out biological detection reaction, used
Or electrolyte can cause more insensitive capacitance to react, and it between the two may be poor hundred times.Therefore, believe by adjusting driving
Number SE, and initial value is set in relevant range, so that it may the biological monitor 20 of the present invention is made to become multiduty biology and is examined
Device 20 is surveyed, can be not limited to that a kind of determinand can only be detected.
For example, as shown in the step S213 of Fig. 3, in the present embodiment, it is preferred that biological monitor 20 judges step
Whether the initial value of rapid S212 is between a relevant range.When this initial value is really between relevant range, then carries out Fig. 2,3 the step of
S22 (is described) again later.If this initial value between relevant range, does not pass through correcting circuit 24 (Fig. 4) output calibration signal
Thus SC adjusts initial value to relevant range (the step S214 for referring to Fig. 3).Thus, the present embodiment will be true
The initial value of biological detection chip 21 is protected in the correct order of magnitude.
In one embodiment, correcting circuit 24 such as, but not limited to can be by adjusting electric current, voltage, resistance or capacitance
It corrects within this initial value to relevant range.
Note that this is that the prior art is lacked.The prior art can not carry out the initial value of biological detection chip 21
Adaptive correction mechanism, therefore the biological monitor of the prior art can only be directed to single kind of determinand of test, can not be mostly used
Way uses.
Next, refering to Fig. 2,3 step S22, in biological detection chip 21, biological respinse solution (example is only first added in
Such as：Buffer solution or electrolyte) but be added without sample survey (i.e. determinand, such as：For hybridization reaction DNA molecular), and
And the first electrical parameter between two parallel poles possessed by measurement biological detection chip 21.Wherein, as described above, this first
Electrical parameter can be capacitance or impedance value (refering to Fig. 2,3 step S22).
Then, Fig. 3 is please refer to, as shown in figure 3, being relevant to this by 22 exportable biological detection chip 21 of detection circuit
The one first output signal (represent only first to add in biological respinse solution but be added without the signal of sample survey) of first electrical parameter
(the step S223 for referring to Fig. 3).Similar to step S211, biological monitor 20 can also input by adjusting circuit 26 at this time
Or adjustment drive signal SE (the step S222 for referring to Fig. 3), to meet the required order of magnitude.It is same as above, it is only for selectivity
The step of (therefore the step S222 of Fig. 3 is illustrated with dashed rectangle).
Herein and the present embodiment point unlike the prior art.As shown in figure 3, biological monitor 20 can be Fig. 3's
The first output signal of step S224 judgment steps S223 (represents only first to add in biological respinse solution but is added without sample survey
Signal) whether reach a basic level for being easy to detection and identification.Reach basic level when the first output signal of step S223 has,
Then carry out the step S23 (describing again later) of Fig. 2.If this first output signal is not reaching to basic level, in the present embodiment, compared with
Goodly, the level of the first output signal by adjusting 26 output drive signal SE of circuit, can thus be adjusted to basic level, so that
First output signal can be detected.
In one embodiment, adjustment circuit 26 such as, but not limited to can utilize DC current, voltage or the week of exchange
Phase and amplitude, for different biological tests objects electrical characteristic come adjust automatically feedback signal so that detection circuit 22 has most preferably
Detection iodine, the level of the first output signal is thus adjusted to basic level, so that the first output signal can be detected
It surveys.
Next, refering to Fig. 2,3 step S23, in biological detection chip 21, while biological respinse solution (example is added in
Such as：Buffer solution or electrolyte) and sample survey (such as：For hybridization reaction DNA molecular), also, measure biological detection
Interelectrode second electrical parameter of two parallel poles possessed by chip 21.Wherein, as described above, this second electrical parameter can be with
It is capacitance or impedance value (the step S23 for referring to Fig. 2).The biological respinse solution added in can be to have been deposited in previous steps
Biological respinse solution, but after also can remove the biological respinse solution of previous steps, then apply again.It is worth noting that：
When the biological respinse solution of previous steps is removed, determinand will not be taken away, therefore does not interfere with readings.
Referring next to Fig. 3, as shown in figure 3, by 22 exportable biological detection chip 21 of detection circuit be relevant to this second
One second output signal (reflection adds in the signal of biological respinse solution and sample survey simultaneously) of electrical parameter is (refering to Fig. 3's
Step S233).Certainly, biological monitor 20 can also input a drive signal SE to biological detection by adjusting circuit 26 at this time
Chip 21 (the step S232 for referring to Fig. 3).It is same as above, be only for selective step (therefore the step S232 of Fig. 3 be with void
Line box illustrates).
Then, please refer to Fig.3.As shown in figure 3, the first of the second electrical parameter of comparison step S23 and step S22 electrically
Difference between parameter determines whether there is the presence for the biomolecule to be detected accordingly.So complete the biology inspection of the present embodiment
Survey method.
It refer to Fig. 5 and compares figure 6.Fig. 5 shows the step flow of the second embodiment of the biological detecting method of the present invention
Figure.Fig. 6 is shown, corresponding to Fig. 5, the block schematic diagram of the second embodiment of biological monitor of the invention.
As shown in fig. 6, biological monitor 30, which includes a biological detection chip 41, one, compares biological detection chip 51, one
Detection circuit 22, a control circuit 23, a correcting circuit 24 and an adjustment circuit 26.In addition, biological monitor 30 may be selected
Property include an analog-to-digital conversion circuit (ADC) 25.Biological monitor 30 in the present embodiment, it is illustrated that is only citing
Include a biological detection chip 21.However, in other embodiments, biological detection chip 21 can be multiple, not limit only
Include a biological detection chip 21.In addition, the biological monitor 30 of the present embodiment and the biological detection of first embodiment fill
20 maximum difference is put to be：The biological monitor 30 of the present embodiment has control biological detection chip 51 (on setting
The feature and advantage of biological detection chip 51 are compareed, is described in detail later).
As shown in figure 5, not yet add biological respinse solution (depending on the biological detection purpose of required progress, such as
But it is not limited to be buffer solution or electrolyte) when, biological monitor 30 first corrects control biological detection chip 51
Initial value (the step S51 for referring to Fig. 5).In addition, similarly, as shown in figure 5, when not yet adding biological respinse solution, biology
Detection device 30 also first corrects the initial value (the step S41 for referring to Fig. 5) of biological detection chip 41.Biological monitor as a result,
Whether the initial value of 30 judgment step S41 and step S51 is between a relevant range, and effect is similar to the biology inspection of first embodiment
Device 20 is surveyed, details are not described herein.
Next, refering to the step S52 of Fig. 5, in compareing in biological detection chip 51, biological respinse solution is only first added in
(such as：Buffer solution or electrolyte) but be added without sample survey (such as：For hybridization reaction DNA molecular), also, measure
Compare the first electrical parameter between two parallel poles possessed by biological detection chip 51.Wherein, as described above, this first electrically
Parameter can be capacitance or impedance value (the step S52 for referring to Fig. 5).As noted previously, as measurement control biological detection chip
The electrical parameter between two parallel poles in 51 has been technology familiar to the person skilled in the art, and details are not described herein.
Similar to the biological monitor 20 of first embodiment, the present embodiment biological monitor 30 equally can interpolate that step
The one first output signal that this first electrical parameter is relevant in rapid S52 (reflects and only first adds in biological respinse solution but be added without
The signal of sample survey) whether reach a basic level (not shown).When this first output signal be not reaching to basic level, this
Thus embodiment equally can adjust the level of the first output signal extremely at this moment by adjusting 26 output drive signal SE of circuit
Basic level, so that the first output signal can be detected.Since effect here is similar to the biological detection of first embodiment
Device 20, details are not described herein.
Next, refering to the step S42 of Fig. 5, in biological detection chip 41, while add in biological respinse solution (such as：
Buffer solution or electrolyte) and sample survey (such as：For hybridization reaction DNA molecular), also, measure biological detection chip
Interelectrode second electrical parameter of two parallel poles possessed by 41.Wherein, as described above, this second electrical parameter can be electricity
Capacitance or impedance value (the step S42 for referring to Fig. 5).
Similar to the biological monitor 20 of first embodiment, the present embodiment biological monitor 30 equally can interpolate that step
The one second output signal that this second electrical parameter is relevant in rapid S42 (reflects while adds in biological respinse solution with examining sample
The signal of product) whether reach a basic level (not shown).When this second output signal is not reaching to basic level, the present embodiment
The level of the second output signal equally at this moment by adjusting 26 output drive signal SE of circuit, can thus be adjusted to substantially electric
Flat (not shown), so that the second output signal can be detected.Certainly, in order to compare, applied in judgment step S42 and S52
Drive signal SE it is preferably identical.
Then, it refer to Fig. 5.As shown in figure 5, the first of the second electrical parameter of comparison step S42 and step S52 electrically
Difference between parameter determines whether there is the presence for the biomolecule to be detected accordingly.So complete the biology inspection of the present embodiment
Survey method.It is worth noting that, the biological monitor 30 of the present embodiment and the biological monitor 20 of first embodiment are not
It is with putting：It (only first adds in biological respinse solution as a blank group using biological detection chip 51 is compareed but is added without inspection
Test sample), to be convenient to the biological detection chip 41 of experimental group (while adding in the signal of biological respinse solution and sample survey)
Measured electrical parameter can directly deduct control biological detection chip 51, make differential design measurement combination with this.So
The detection circuit 22 of biological monitor 30 is a comparator, to the second electrical parameter and the step S52 of comparison step S42
The first electrical parameter between difference.First embodiment can be considered a kind of method of sequentially formula, and second embodiment can be considered
A kind of method of run-in index.
It refer to Fig. 7~10.Fig. 7 marks the 3rd embodiment of the biological monitor of the present invention.Fig. 8 marks the present invention's
The fourth embodiment of biological monitor.Fig. 9 marks the 5th embodiment of the biological monitor of the present invention.Figure 10 marks this hair
The sixth embodiment of bright biological monitor.
In order to increase the susceptibility of measurement, the present invention still makes biological detection in a manner of by packaged type or PCB
Device 40 such as, but not limited to may include a multiplexer 27 (as shown in Figure 7), and multiple biological detection chips are controlled with multitask
41 compare biological detection chip 51 with one, and plurality of biological detection chip 41 is such as, but not limited to can be designed as the square of 1x N
Battle array arrangement (as shown in Figure 7).
Alternatively, as shown in figure 8, biological monitor 50 such as, but not limited to may include at least two multiplexers 28 and 29,
With multitask multiple biological detection chips 41 is controlled to compare biological detection chip 51 with one.Plurality of biological detection chip 41
As but be not limited to can be designed as the matrix arrangement (as shown in Figure 8) of N x N.
Biological monitor 60 as shown in Figure 9, biological detection chip 41 such as, but not limited to can be multiple, and example
Such as but it is not limited to can be designed as to arrange in a series arrangement.Alternatively, biological monitor 70 as shown in Figure 10, biological detection core
Piece 41 such as, but not limited to can be multiple, and such as, but not limited to can be designed as arranging with parallel way.
It is worth noting that, the biological monitor 40,50,60 and/or 70 shown in Fig. 7~10 all has above-described embodiment
Biological monitor 20 and 30 the advantages of and effect, and more can one-time detection obtain multiple data.
Compared with the prior art, the present invention can be directed to the detection that different determinands carries out wide scope, and step is than existing
Have that technology is simple, and error will not be caused because determinand is taken away in cleaning in detection process.Further, it is also possible to it once obtains
More data, therefore better than the prior art.
Illustrate the present invention for preferred embodiment above, but it is described above, only it is easy to those skilled in the art
Understand present disclosure, be not used for limiting the interest field of the present invention.Under the same spirit of the present invention, art technology
Personnel are contemplated that various equivalence changes.For example, between the shown circuit element being directly connected to, can plant does not influence the main work(of circuit
The circuit element of energy, such as switch or resistance.Again for another example, a signal is handled inside circuit or during computing, may be passed through
Therefore Voltage to current transducer, Current Voltage conversion, ratio conversion, level conversion etc., " carry out alleged by the present invention according to certain signal
Processing or computing ", be not limited to according to the signal itself, also comprising when necessary, after which is carried out above-mentioned conversion, according to
Transformed signal is handled or computing.In every case it is such, it according to the present invention can all teach and analogize and obtain.It is in addition, illustrated
Each embodiment, however it is not limited to be used alone, can also combination application, such as, but not limited to two embodiments are used in combination.Therefore,
The scope of the present invention should cover above-mentioned and other all equivalence changes.In addition, any implementation kenel of the present invention is necessarily realized
All purposes or advantage, therefore, any one of claim also should not be as limit.
Claims (22)
1. a kind of biological detecting method, which is characterized in that include：
(A) in no added one biological reaction solution, an initial value of a biological detection chip is corrected in advance；
(B) in the biological detection chip, only first add in the biological respinse solution but be added without a sample survey, also, measure
Interelectrode one first electrical parameter possessed by the biological detection chip；
(C) in the biological detection chip, while the biological respinse solution and the sample survey are added in, also, measures the biology
Interelectrode one second electrical parameter possessed by detection chip；And
(D) difference between second electrical parameter of comparison step (C) and first electrical parameter of step (B), sentences accordingly
The fixed presence for whether having the biomolecule to be detected.
2. biological detecting method as described in claim 1, wherein, which includes：
(A1) initial value of the biological detection chip is exported；
(A2) judge the initial value whether between a relevant range；
(A3) when the initial value is between the relevant range, the step (B) is carried out；And
(A4) when the initial value is not between the relevant range, correct within the initial value to the relevant range.
3. biological detecting method as described in claim 1, wherein, which further includes：A drive signal is inputted to the life
Analyte detection chip.
4. biological detecting method as described in claim 1, wherein, which includes：
(B1) the output phase exports signal on the one first of first electrical parameter；
(B2) judge whether the first output signal reaches a basic level；
(B3) when this first output signal be to reach the basic level, carry out the step (C)；And
(B4) when the first output signal is not reaching to the basic level, the level for adjusting the first output signal is substantially electric to this
It is flat.
5. biological detecting method as claimed in claim 4, wherein, which further includes：A drive signal is inputted to the life
Analyte detection chip.
6. biological detecting method as described in claim 1, wherein, which includes：
(C1) the output phase exports signal on the one second of second electrical parameter.
7. biological detecting method as claimed in claim 6, wherein, which further includes：A drive signal is inputted to the life
Analyte detection chip.
8. biological detecting method as described in claim 1, wherein, which includes a buffer solution or an electrolysis
Liquid.
9. biological detecting method as described in claim 1, wherein, first electrical parameter and second electrical parameter wrap respectively
Include an impedance value or a capacitance.
10. a kind of biological monitor, which is characterized in that include：
An at least biological detection chip, to contain a biological reaction solution and/or a sample survey；
One detection circuit, to export an initial value of the biological detection chip and/or a measuring signal, wherein, measurement letter
Number include：
One first electrical parameter is in the biological detection chip, only first adds in the biological respinse solution but be added without the inspection
When testing sample, for the measuring signal measured between electrode possessed by the biological detection chip；And/or
One second electrical parameter is in the biological detection chip, while adds in the biological respinse solution and the sample survey
When, for the measuring signal measured between electrode possessed by the biological detection chip；
One control circuit, to judge the initial value of the biological detection chip whether between a relevant range or according to the measurement
Signal, judges whether the one first output signal for being relevant to first electrical parameter reaches a basic level；
One correcting circuit to the judging result according to the control circuit, is examined in no added one biological reaction solution to biology
When surveying chip, correct in advance within the initial value to the relevant range；And
One adjustment circuit, to the judging result according to the control circuit, the level for adjusting the first output signal is basic to this
Level.
11. biological monitor as claimed in claim 10, wherein, which further includes a multiplexer, uses
Multiple biological detection chips are controlled with multitask, wherein the plurality of biological detection chip is with the matrix arrangement of 1 x N.
12. biological monitor as claimed in claim 10, wherein, which further includes at least two multitasks
Device controls multiple biological detection chips, wherein the plurality of biological detection chip is with the matrix arrangement of N x N to multitask.
13. biological monitor as claimed in claim 10, wherein, which is multiple, and the plurality of life
Analyte detection chip is with arranged in series.
14. biological monitor as claimed in claim 10, wherein, which is multiple, and the plurality of life
Analyte detection chip is to be arranged in parallel.
15. biological monitor as claimed in claim 10, wherein, which includes a buffer solution or an electricity
Solve liquid.
16. biological monitor as claimed in claim 10, wherein, first electrical parameter and second electrical parameter difference
Including an impedance value or a capacitance.
17. a kind of biological detecting method, which is characterized in that include：
(A) in no added one biological reaction solution, one first initial value of one control biological detection chip of correction in advance；
(B) in the control biological detection chip, only add in the biological respinse solution but be added without a sample survey, also, survey
Measure interelectrode one first electrical parameter possessed by the control biological detection chip；
(C) in the no added biological respinse solution, one second initial value of a biological detection chip is corrected in advance；
(D) in the biological detection chip, while the biological respinse solution and the sample survey are added in, also, measures the biology
Interelectrode one second electrical parameter possessed by detection chip；And
(E) difference between second electrical parameter of comparison step (D) and first electrical parameter of step (B), sentences accordingly
The fixed presence for whether having the biomolecule to be detected.
18. biological detecting method as claimed in claim 17, wherein, which includes a buffer solution or an electricity
Solve liquid.
19. biological detecting method as claimed in claim 17, wherein, first electrical parameter and second electrical parameter difference
Including an impedance value or a capacitance.
20. a kind of biological monitor, which is characterized in that include：
One control biological detection chip, to contain a biological reaction solution；
An at least biological detection chip, to contain a biological reaction solution and/or a sample survey；
One detection circuit, to export the 1 of one first initial value of the control biological detection chip or the biological detection chip
Two initial values and to compare the 1 of one first measuring signal of the control biological detection chip and the biological detection chip
Difference between two measuring signals；
Wherein, which includes：
One first electrical parameter is in the control biological detection chip, only first adds in the biological respinse solution but be added without
During the sample survey, for first measuring signal measured between electrode possessed by the control biological detection chip；
Wherein, which includes：
One second electrical parameter is in the biological detection chip, while adds in the biological respinse solution and the sample survey
When, for second measuring signal measured between electrode possessed by the biological detection chip；
One control circuit, to judge first initial value of the control biological detection chip or the biological detection chip this
Whether two initial values judge be relevant to first electrical parameter one first defeated between a relevant range or according to the measuring signal
Go out whether signal reaches a basic level；
One correcting circuit to the judging result according to the control circuit, is given birth in no added biological respinse solution to the control
When analyte detection chip or the biological detection chip, first initial value or second initial value are corrected in advance respectively to the appropriate model
Within enclosing；And
One adjustment circuit, to the judging result according to the control circuit, the level for adjusting the first output signal is basic to this
Level.
21. biological monitor as claimed in claim 20, wherein, which further includes a multiplexer, uses
The control biological detection chip and multiple biological detection chips are controlled with multitask, wherein the control biological detection chip and this is more
A biological detection chip is with the matrix arrangement of 1 x N.
22. biological monitor as claimed in claim 20, wherein, which further includes at least two multitasks
Device controls the control biological detection chip and multiple biological detection chips, wherein the control biological detection chip to multitask
And the plurality of biological detection chip is with the matrix arrangement of N x N.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15/724,076 US20180143153A1 (en) | 2016-11-23 | 2017-10-03 | Bio-cell detection apparatus and bio detection method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662426151P | 2016-11-23 | 2016-11-23 | |
| US62/426,151 | 2016-11-23 |
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