Magnetic sensor device, method of operating such a device and sample

• US 9,557,328 B2
• Filed: 06/24/2010
• Issued: 01/31/2017
• Est. Priority Date: 06/30/2009
• Status: Active Grant

• Current Assignee: Siemens Healthcare Nederland B.V. (Siemens AG)
• Original Assignee: Koninklijke Philips N.V.
• Inventors: Dittmer, Wendy Uyen, De Theije, Femke Karina, Immink, Albert Hendrik Jan, Nieuwenhuis, Jeroen Hans, Van Lankvelt, Petrus Johannes Wilhelmus
• Primary Examiner(s): Martinez, Rebecca
• Application Number:
  US13/381,115
• Publication Number:
  US 20120107961A1
• Time in Patent Office: 2,413 Days
• Field of Search: 436/525, 436/526
• US Class Current: 1/1
• 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 for detecting the presence of a target molecule in a stationary sample, the sensor device comprising:

a measurement sensor including a first moiety including a measurement region of a substrate including a first moiety, which is a paratope, which selectively binds to an epitope of the target molecule including a further epitope, which can bind with a paratope present on a first further moiety comprising a detectable label, wherein an amount of the first further moiety binding to the first moiety is related to an amount of the target molecule present in said sample, the measurement sensor being configured to generate a first detection signal in response to detection of the detectable label in the first further moiety bound to the first moiety; and

a reference sensor including a reference region of the substrate including a second moiety which selectively binds to a second further moiety including a further detectable label, the reference sensor being configured to generate a second detection signal in response to detection of the further detectable label in the second further moiety bound to the second moiety;

a signal processor configured to;

during operation of the sensor device, determine whether the second detection signal falls within a signal value window corresponding to a predefined amount of the second further moiety binding to the second moiety; and

in response to the second detection signal falling outside the signal value window, generating a failure signal indicative of any of completion failure of the assay, insufficient fluid added to the test, incorrect preparation of the actuation protocol of the assay, lack of magnetic particles in the cartridge, failure of dry agents to disperse, unusually high clusters of magnetic particles, extensive reagent degradation, integrated reagent deterioration, or a damaged assay cartridge; and

a speaker or display which issues an audible or visible output in response to the failure signal.

2. The sensor device of claim 1, wherein the detectable label of the first moiety and the further detectable label of the second moiety are the same, and wherein the second further moiety is also comprised in the first 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 of claim 1, wherein the measurement sensor is located in a first measurement chamber and the reference sensor is located in a second measurement chamber.

5. The sensor device of claim 1, wherein the second further moiety is in a dried form and wherein a known amount of the second further moiety is added to the sample.

6. The sensor device of claim 1, wherein the second moiety and the second further moiety are selected from the group of hapten-antibody pairs including biotin-antibiotin, fluorescinisothiocyanate-anti fluorescinisothiocyanate and Texas Red-antiTexas Red;

antibody-antiantibody pairs and small molecule-protein pairs;

wherein the anti-antibodies can bind to both light and heavy chains on multiple regions of the antibody.

7. The sensor device of claim 1, wherein the second further moiety further includes a reference molecule having a substantially constant concentration in samples that contain the target molecule in varying concentrations.

8. The sensor device of claim 1, wherein the sensor device is a magnetic sensor device and the label includes a magnetic particle and the further label includes a further magnetic particle, and wherein the magnetic sensor device includes 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 and the second moiety are attached to respective binding surfaces of a carrier, the sensor device further comprising:

a light source configured to emit an input light beam into the carrier which arrives at least at one of the binding surfaces at an angle larger than a critical angle of total internal reflection such that the light beam is totally internally reflected as output light beams leaving the carrier through another surface and, in response to the totally internally reflected light beam becoming frustrated, an intensity of the totally internally reflected light decreases in response to the label and/or the further label macroscopically scattering and/or absorbing the magnetic particles; and

a light detector for determining an amount of light in an output light beam that includes at least some of the frustrated totally internally reflected light, said light detector being configured to generate at least one of the first detection signal and the second detection signal.

10. The apparatus of claim 1, wherein a reference signal value derived from the second detection signal is a time-varying value based on a time-varying behavior of the second detection signal.

11. The apparatus of claim 10, wherein:

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

said failure signal is based on said comparison.

12. The apparatus of claim 11, wherein the signal processor stage is further configured 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; and

determine a target molecule concentration from the correction factor and the measurement value.