Reaction detection system

• US 3,989,383 A
• Filed: 04/07/1975
• Issued: 11/02/1976
• Est. Priority Date: 04/07/1975
• Status: Expired due to Term

• Current Assignee: Bio-Technology Instruments Corporation
• Original Assignee: Bio-Technology Instruments Corporation
• Inventors: Paulson, Gerald Lee
• Primary Examiner(s): Corbin, John K.
• Assistant Examiner(s): Hille, Rolf
• Application Number:
  US05/565,665
• Time in Patent Office: 575 Days
• Field of Search: 356/96, 356/97, 356/201, 23/230 R, 23/230 B, 195/103.5 R
• US Class Current: 356/414
• CPC Class Codes: G01N 21/272 for following a reaction, e.g. for determining photometrically a reaction rate (photometric cinetic analysis)
• CPC Class Codes: G01R 17/04 in which the reference value is continuously or periodically swept over the range of values to be measured

Abstract

A system for detecting the reaction rate of change of a solution. Enzyme activity of a sample may be measured by such a system. In the system, the light transmittance characteristic of the sample changes in accordance with the reaction change. Detection circuitry detects the variation in light absorbance and develops an electrical signal which varies in accordance with the absorbance, thus varying in accordance with the reaction change. First sampling circuitry samples the electrical signal at predetermined first intervals and develops a first sampling signal during that sampling which is proportional to the electrical signal. This first sampling signal is held in the first sampling circuitry until the following sampling. Second sampling circuitry samples the first sampling signal at predetermined intervals and develops a second sampling signal during the sampling which is proportional to the first sampling signal. The second sampling signal is held in the second sampling circuitry until the following sampling. The first and second sampling signals are summed to develop an output signal which represents the difference between the first and second signals and is therefore an indication of the reaction rate of change between sampling intervals. A scaling factor is added to this output signal for converting the signal into known and recognized units such as optical absorbance and the converted signal is displayed on a display device.

Claims

1. In a reaction detection system for determining the reaction rate of a sample wherein said reaction is represented by an electrical input signal which can vary in accordance with said reaction during a predetermined time increment, the combination including;

input means for receiving said electrical input signal,

first sampling means coupled to said input means and operative at predetermined first intervals to sample said electrical input signal and develop a first sampling signal during said sampling proportional to said electrical input signal and to hold said first sampling signal until the following sampling,

second sampling means coupled to said first sampling means and operative at predetermined second intervals to sample said first sampling signal and develop a second sampling signal during said sampling proportional to said first sampling signal and to hold said sampling signal until the following sampling,

summing circuit means coupled to said first and second sampling means and operative to develop an output signal representing the difference between said first and second sampling signals, and

display means coupled to said summing means and operative in response to said output signal to display an output proportional to said output signal.

2. The reaction detection system of claim 1 wherein said first sampling means include,

a sample and hold circuit for sampling said electrical input signal, developing said first sampling signal and storing the same, and

gating means coupled to said input means and said sample and hold circuit and operative at said predetermined first intervals to couple said input means to said sample and hold circuit.

3. The reaction detection system of claim 2 further including, clock means for developing first clock pulses at predetermined intervals, said gating means being coupled to said clock means and operative in response to said clock pulses to couple said input means to said sample and hold circuit.

4. The reaction detection system of claim 2 wherein said sample and hold circuit includes capacitor means coupled to said gate means for developing a voltage thereacross proportional to said electrical input signal and amplfier means coupled to said capacitor means for amplifying said voltage.

5. The reaction detection system of claim 1 wherein said second sampling means include,

a sample and hold circuit for sampling said first sampling signal, developing said second sampling signal and storing same, and

gating means coupled to said first sampling means and said sample and hold circuit and operative at said predetermined second intervals to couple said first sampling means to said sample and hold circuit.

6. The reaction detection system of claim 5 further including, clock means for developing second clock pulses at predetermined intervals, said gating means being coupled to said clock means and operative in response to said clock pulses to couple said first sampling means to said sample and hold circuit.

7. The reaction detection system of claim 5 wherein said sample and hold circuit includes capacitor means coupled to said gating means for developing a voltage thereacross proportional to said first sampling signal and amplifier means coupled to said capacitor means for amplifying said voltage.

8. The reaction detection system of claim 1 wherein said summing circuit means include, first resistor means having a first terminal coupled to said first sampling means and the second terminal, and second resistor means having a first terminal coupled to said second sampling means and a second terminal coupled to said first resistor means second terminal, said output signal being developed at said first and second resistor means second terminals.

9. The reaction detection system of claim 1 further including,

third sampling means coupled to said summing means and operative at predetermined third intervals to sample said output signal and develop a third sampling signal during said sampling proportional to the output signal and to hold said third sampling signal until the following sampling,

comparing means coupled to said summing means and operative to compare said third sampling signal and said output signal and develop a comparison signal in accordance with variations between said output and said third sampling signal, and

indicator means coupled to said comparing means and operative in response to said comparison signal to indicate a variation between said output signal and said third sampling signal whereby an indication of the variation from linear reaction rate of change is provided.

10. The reaction detection system of claim 9 further including clock means coupled to said first, second and third sampling means and operative to develop first, second and third clock pulses at predetermined intervals, each having a predetermined repetition rate and period, said first, second and third sampling means operative in response to said first, second and third clock pulses respectively to sample and develop said sampling signals.

11. The reaction detection system of claim 10 wherein said predetermined intervals are equal.

12. The reaction detection system of claim 9 wherein said third sampling means include,

a sample and hold circuit for sampling said signal, developing said third sampling signal and storing same, and

gating means coupled to said summing means and said sample and hold circuit and operative at said predetermined third intervals to couple said summing means to said sample and hold circuit.

13. The reaction detection system of claim 12 further including, clock means for developing third clock pulses at predetermined intervals, said gating means being coupled to said clock means and operative in response to said clock pulses to couple said summing means to said sample and hold circuit.

14. The reaction detection system of claim 12 wherein said sample and hold circuit includes capacitor means for developing a voltage thereacross proportional to said summing signal and amplifier means coupled to said capacitor means for amplifying said voltage.

15. The reaction detection system of claim 9 wherein said comparing means include first resistor means having a first terminal coupled to said summing means and a second terminal and second resistance means having a first terminal coupled to said third sampling means and a second terminal coupled to said first resistance means second terminal.

16. A system for detecting the reaction rate of change of a solution whose optical opacity changes in accordance with the reaction change therein including in combination,

means for developing an electrical signal which varies in accordance with said reaction changes,

first sampling means coupled to said means for developing an electrical signal and operative at predetermined first intervals to sample said electrical signal and develop a first sampling signal during said sampling proportional to said electrical signal and to hold said first sampling signal therein until the following sampling,

second sampling means coupled to said first sampling means and operative at predetermined second intervals to sample said first sampling signal and develop a second sampling signal during said sampling proportional to the first sampling signal and to hold said second sampling signal until the following sampling,

summing circuit means coupled to said first and second sampling means and operative to develop an output signal representing the difference between said first and second signals, and

display means coupled to said summing means and operative in response to said output signal to develop an output display proportional to said output signal.

17. The system of claim 16 wherein said means for developing an electrical signal include,

a light source,

means for passing light from said light source through said solution, the light intensity passing through said solution varying in accordance with said reaction change, and

detector means for receiving said passed light and developing said electrical signal, said electrical signal varying in accordance with the intensity of said passed light.

18. The system of claim 17 wherein said means for passing light include, means for containing said solution, said means having at least two transparent portions for transmitting said light therethrough and through said solution.

19. The system of claim 18 wherein said means for developing an electrical signal further include,

chopper means for chopping said light at a regular repetition rate,

filter means for passing particular light wavelengths, the intensity of said particular wavelengths of passed light varying in accordance with the reaction rate of change of said solution,

said detector means including photodetector means positioned to receive said paritcular wavelengths of light and operative to develop an electrical photodetector signal which varies in accordance with said passed light intensity and said chopper repetition rate.

filter means coupled to said photodetector means and operative to filter said photodetector signal, to develop a detection signal, and

converter means for converting said detection signal to said electrical signal.

20. The system of claim 17 wherein said solution reaction rate of change is logarithmic, said means for developing an electrical signal including logarithmic amplifier means operative to convert said logarithmic change and develop said electrical signal having a linear reaction rate of change.

21. The system of claim 20 wherein said means for developing an electrical signal further include means for detecting said reaction change and developing a signal that varies in accordance with said reaction change, first signal adjusting means coupling said detecting means to said logarithmic amplifier means and adjustable for selecting a predetermined detection signal amplitude prior to each solution reaction, said system further including, first switching means coupling said logarithmic amplifier means to said first sampling means for selectively connecting said amplifier to said first sampling means, reference generator means coupled to said switching means and selectively operable to develop a reference electrical signal having a predetermined time rate of change and couple same to said first sampling means for establishing a reference rate of change for said system, and second switching means coupling said summing circuit means, said logarithmic amplifier means, and said first signal adjusting means to said display means for selectively displaying, said output proportional to said output signal, said electrical signal from said logrithmic amplifier and said adjusted detection signal from said first signal adjusting means.

22. The system of claim 16 further including, third sampling means coupled to said summing means and operative at predetermined third intervals to sample said output signal and develop a third sampling signal during said sampling proportional to the output signal and to hold said third sampling signal until the following sampling, comparing means coupled to said summing means and operative to compare said third sampling signal and said output signal and develop a comparison signal in accordance with the variations between said output signal and said third sampling signal, and indicator means coupled to said comparing means and operative in response to said comparison signal to indicate a variation between said output signal and said third sampling signal whereby an indication of variations in linear operation is provided.

23. The system of claim 22 further including clock means coupled to said first, second and third sampling means and operative to develop first, second and third clock pulses at predetermined intervals each having a predetermined repetition rate and period, said first, second and third sampling means operative in response to said first, second and third clock pulses respectively to sample and develop said sampling signals.

24. The system of claim 23 wherein said predetermined time intervals are equal and wherein each said first clock pulse succeeds each said second clock pulse in time and each said second clock pulse succeeds each said third clock pulse in time.