Apparatus and method for measuring optical properties by feedback control

• US 6,723,554 B1
• Filed: 05/26/2000
• Issued: 04/20/2004
• Est. Priority Date: 11/26/1997
• Status: Expired due to Term

• Current Assignee: Institut Pasteur
• Original Assignee: Institut Pasteur
• Inventors: Longin, Robert, Luu, Thanh Dung, Gaillon, Laurent
• Primary Examiner(s): Redding, David A.
• Application Number:
  US09/554,110
• Time in Patent Office: 1,425 Days
• Field of Search: 422/82.05, 422/82.09, 435/286.1, 435/288.7, 250/458.1, 356/300, 356/432, 356/445, 356/317, 356/318, 356/337, 356/451
• US Class Current: 435/288.7
• CPC Class Codes: C12M 23/08 Flask, bottle or test tube
• CPC Class Codes: C12M 23/38 Caps; Covers; Plugs; Pouring means
• CPC Class Codes: C12M 29/26 Conditioning fluids entering or exiting the reaction vessel
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence

Abstract

The invention concerns an apparatus and a method for measuring at least one optical characteristic, which can include in particular turbidity (T), absorbance (A) and fluorescence (F), of a medium (1), and a micro-bioreactor, a connector and associated male and female parts. The apparatus comprises a light source (3) provided with means for controlling (6) the intensity of the beam transmitted (11) by the source, a photodetector (4) for measuring the intensity of the beam reflected (12) by the medium, a feedback regulating system (7) operating on the control means such that the measured intensity of the reflected beam is equal to a predetermined nominal intensity, and means for reading the transmitted beam intensity, said intensity representing the medium optical characteristic(s). The apparatus also comprises means for adjusting the nominal intensity, such that the transmitted beam stabilised intensity is within a predetermined range. The invention is applicable to micro-bioreactors.

Claims

1. Apparatus for determining at least one optical property of a medium, comprising:

a light source configured to provide a transmitted beam that is transmitted towards and into the medium;

a detector configured to measure intensity of a modified beam exiting from the medium,

a control unit configured to control the intensity of the beam transmitted by the light source,

a processing unit configured to provide a representative value of a nominal intensity of the modified beam, and

a feedback regulating system linked to the control unit, the detector, and the processing unit, and configured to control operation of the control unit so that the measured intensity of the modified beam is made equal to the nominal intensity to establish a stabilised intensity for the transmitted beam,

wherein the processing unit is further configured to adjust the representative value of the nominal intensity so that the stabilised intensity of the transmitted beam falls within a predetermined range.

2. The apparatus according to claim 1, wherein the processing unit includes a storage unit designed to store a saturation intensity and to adjust the representative value of the nominal intensity to a lower value when the stabilised intensity of the transmitted beam is higher than the saturation intensity.

3. The apparatus according to claims 1 or 2, wherein the light source and/or the detection means are designed to measure the intensity of the modified beam around at least one wavelength corresponding to said at least one optical property.

4. The apparatus according to claim 1, wherein said at least one optical property comprises turbidity.

5. The apparatus according to claim 4, wherein the light source and/or the detection means have a wavelength around 880 nm.

6. The apparatus according to claim 1, wherein said at least one optical property comprises absorbance.

7. The apparatus according to claim 1, wherein said at least one optical property comprises fluorescence.

8. The apparatus according to claim 1 further comprising a storage device configured to store at least one equation determined by a calibration curve giving said at least one optical property as a function of the intensity of the transmitted beam for at least one respective value of the intensity of the modified light beam wherein the processing unit calculates said optical property from the stabilised intensity of the transmitted light beam for said at least one respective value of the nominal intensity and the equation.

9. The apparatus according to claim 8, wherein the processing unit comprises a central processing unit and at least one card configured to provide analogue/digital and digital/analogue conversion and to couple the central processing unit to the control unit and the feedback regulating system.

10. The apparatus according to claim 1, further comprising a clock, a recording unit, and a repeated activation unit configured to repeatedly activate the feedback regulating system and the recording unit.

11. The apparatus according to claim 1, wherein the feedback regulating system and the control unit are configured to provide continuous equalisation of the measured intensity and the nominal intensity of the modified beam.

12. Micro-bioreactor (20, 41-48) including an apparatus according to claim 1.

13. Micro-bioreactor according to claim 12, further comprising:

a tube closed by a stopper configured to contain a culture,

a first pipe configured to inject sterile air or gas and a culture medium into the culture, and

a second pipe, configured to remove effluents, wherein the tube and the pipes are under pressure.

14. Micro-bioreactor according to claim 13, further comprising a dilutation system designed to dilute the culture on a cyclic basis controlled by the processing unit.

15. Micro-bioreactor according to claim 14, wherein the processing unit repeatedly activates the feedback regulating system, records representative values of said at least one optical property in a storage unit, and triggers the dilution system when a stagnation of said at least one optical property over a plurality of the latest recorded values is observed.

16. Micro-bioreactor according to claim 13 wherein, at least one of the pipes includes a connector comprising a male part female part, a connection part configured to connect said male part and said female part together, each of said male and female parts comprising:

a tapered hollow end configured to be connected to one end portion of said at least one of the pipes, and

a sleeve surrounding a coupling hollow part communicating with said tapered hollow end, the coupling hollow part of the male part being introduced into the coupling hollow part of the female part, with the sleeve of one of the parts being introduced into the sleeve of the other part so that said sleeves are connected to each other by the connection part.

17. Micro-bioreactor according to claim 16, wherein the sleeve of the male part is introduced into the sleeve of the female part.

18. Micro-bioreactor according to claim 16, wherein the connection part includes a locking ring.