MAGNETIC SENSOR DEVICE, METHOD OF OPERATING SUCH A DEVICE AND SAMPLE

• US 20120107961A1
• Filed: 06/24/2010
• Published: 05/03/2012
• Est. Priority Date: 06/30/2009
• Status: Active Grant

• Current Assignee: Siemens Healthcare Nederland B.V. (Siemens AG)
• Original Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Inventors: Dittmer, Wendy Uyen, De Theije, Femke Karina, Immink, Albert Hendrik Jan, Nieuwenhuis, Jeroen Hans, Van Lankvelt, Petrus Johannes Wilhelmus
• Granted Patent: US 9,557,328 B2
• Time in Patent Office: Days
• US Class Current: 436/501
• CPC Class Codes: G01N 21/552 Attenuated total reflection
• CPC Class Codes: G01N 27/745 for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01N 33/54326 Magnetic particles
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54386 Analytical elements

Abstract

A sensor device (1) for detecting the presence of a target molecule (20) in a sample, is disclosed. The sensor device comprises a measurement sensor (2) comprising a first moiety (16) for forming a binding couple with a first further moiety comprising the target molecule (20) and a detectable label (40) and a reference sensor (3) comprising a second moiety (50) for forming a further binding couple with a second further moiety comprising a further detectable label (40′). The sensor device is adapted to generate a first detection signal (14) from the detection of the detectable label (40) in the first further moiety bound to the first moiety (16) and to generate a second detection signal (14′) from the detection of the further detectable label (40′) in the second further moiety bound to the second moiety (50), wherein at least during operation of the sensor device the second further moiety is expected to be present in a predefined amount such that the value of the second detection signal (14′) falls within an expected signal value window when the binding reaction of the second further moiety to the second moiety takes place as expected. An apparatus comprising such a sensor device, methods of operating the sensor device and apparatus and a sample for use with the sensor device are also disclosed.

Claims

1. A sensor device (1) for detecting the presence of a target molecule (20) in a stationary sample, comprising:

a measurement sensor (2) comprising a first moiety (16) for selectively binding to a first further moiety comprising a detectable label (40), the amount of the first further moiety binding to the first moiety being related to the amount of the target molecule (20) present in said sample; and

a reference sensor (3) comprising a second moiety (50) for selectively binding to a second further moiety comprising a further detectable label (40′

), said sensor device being adapted to;

generate a first detection signal (14) from the detection of the detectable label (40) in the first further moiety bound to the first moiety (16); and

generate a second detection signal (14′

) from the detection of the further detectable label (40′

) in the second further moiety bound to the second moiety (50), wherein at least during operation of the sensor device the second further moiety is expected to be present in a predefined amount such that the value of the second detection signal (14′

) falls within an expected signal value window when the binding reaction of the second further moiety to the second moiety takes place as expected.

2. The sensor device of claim 1, wherein the detectable label (40) and the further detectable label are the same, and wherein the first further moiety comprises the target molecule and the second further moiety.

3. The sensor device of claim 1, wherein the first further moiety has no significant affinity for the second moiety and the second further moiety has no significant affinity for the first moiety.

4. The sensor device (1) of claim 1, wherein the measurement sensor (2) is located in a first measurement chamber and the reference sensor (3) is located in a second measurement chamber.

5. The sensor device (1) of claim 1, further comprising the second further moiety in a dried form.

6. The sensor device (1) of claim 1, wherein the second moiety and the second further moiety areselected from the group of hapten-antibody pairs such as biotin-antibiotin, fluorescinisothiocyanate-anti fluorescin isothiocyanate and Texas Red-antiTexas Red;

antibody-antiantibody pairs and small molecule-protein pairs such as avidin-biotin.

7. The sensor device (1) of claim 1, wherein the second further moiety further comprises a reference molecule (60) having a substantially constant concentration in samples suspected to contain the target molecule (20) in varying concentrations.

8. The sensor device (1) of claim 1, wherein the sensor device is a magnetic sensor device, the label comprises a magnetic particle and the further label comprises a further magnetic particle, and wherein the magnetic sensor device comprises a magnetic field generator for attracting the magnetic particle and the further magnetic particle to the respective sensors.

9. The sensor device of claim 8, wherein the first moiety (16) and the second moiety (50) are attached to respective binding surfaces of a carrier, the sensor device further comprising:

a light source (6, 6′

) for emitting an input light beam (L1) into the carrier such that it is totally internally reflected in an investigation region at least one of said binding surfaces, the totally internally reflected light beam becoming frustrated resulting in a decrease of the totally internally reflected light intensity when the label and/or the further label are macroscopic scattering and/or absorbing magnetic particles (40, 40′

); and

a light detector (12, 12′

) for determining the amount of light in an output light beam (L2) that comprises at least some of the frustrated totally internally reflected light, said light detector (12, 12′

) being adapted to generate at least one of the first detection signal (14) and the second detection signal (14′

).

10. An apparatus (100) comprising the sensor device (1) as claimed in claim 1 and a signal processor stage (110) coupled to receive the second detection signal from the sensor device, said signal processor stage (110) being adapted to:

determine a reference signal value from said second detection signal (14′

); and

produce an output signal (120) based on said reference signal value.

11. The apparatus (100) of claim 10, wherein the reference signal value is a time-varying value based on the time-varying behavior of the second detection signal.

12. The apparatus (100) of claim 10, wherein:

the signal processor stage (110) is further adapted to compare the reference signal value with an expectation value based on the expected amount of the second further moiety; and

said output signal (120) is based on said comparison.

13. The apparatus (100) of claim 10, wherein the signal processor stage (110) is further adapted to:

determine a correction factor from a difference between the expectation value and the reference signal value;

determine a measurement value from the first detection signal (14); and

determine a target molecule concentration from the correction factor and the measurement value, wherein said output signal (120) comprises the determined target molecule concentration.

14. A method of operating an apparatus (100) as claimed in claim 10, the method comprising:

generating a first detection signal (14) from the detection of the detectable label (40) in the first further moiety bound to the first moiety (16);

generating a second detection signal (14′

) from the detection of the further detectable label (40′

) in the second further moiety concentration bound to the second moiety (50);

determining (610) a reference signal value from said second detection signal (14′

); and

producing (640, 650) an output signal (120) based on said reference signal value.

15. The method of claim 14, further comprising:

comparing (620) the reference signal value with an expectation value;

determining (710) a correction factor from a difference between the expectation value and the reference signal value;

generating the first detection signal;

determining (720) a measurement value from the first detection signal; and

determining (730) a target molecule concentration from the measurement value and the correction factor, wherein said output signal comprises the determined target molecule concentration.