Integrated Membrane Sensor

• US 20080199971A1
• Filed: 02/01/2008
• Published: 08/21/2008
• Est. Priority Date: 02/01/2007
• Status: Active Grant

• Current Assignee: Diagnostic Biosensors LLC
• Original Assignee: Diagnostic Biosensors LLC
• Inventors: Tondra, Mark Christopher
• Granted Patent: US 8,753,894 B2
• Time in Patent Office: Days
• US Class Current: 436/149
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01R 33/12 Measuring magnetic properties of articles or specimens of solids or fluids involving magnetic resonance G01R33/20
• CPC Class Codes: G01R 33/1269 of molecules labeled with magnetic beads magnetic particles for bio assay G01N33/54326

Abstract

An integrated microelectronic sensor is provided in a disposable flow membrane sensing device. The integrated sensors detect electromagnetic effect labels in flow detection zones above the sensor in the membrane. The labels are small particles that give off a detectable electromagnetic signal. They are commonly used for isolating and quantifying biochemical targets of interest. The sensors are fabricated using planar integrated circuit technologies. Sensors can detect labels of several types including magnetic, electric, and photonic. These types all have in common the fact that the sensor detects the label at a distance. Magnetoresistive sensors for detecting magnetic labels, and photodiodes for detecting photonic labels are described.

A system for using the sensors is described. There are disposable cartridges with a backing that supports the sensors and membrane is described. The integrated sensor in the cartridge is designed to be discarded after use. Also, label excitation sources are provided. The multi sensor array chip can be configured in order to detect labels in multiple zones, and to monitor progress of flow down a strip of membrane. These multiple label detection zones, using sandwich assay techniques, can quantify analyte concentration for many types of analytical samples. Also, the membrane can be micropatterned in order to provide multiple or unusually shaped flow paths.

Claims

1. An electromagnetic effect field detection system for measuring labels in a fluid comprising:

a planar substrate;

at least one electromagnetic effect field sensor formed on a first surface of the substrate; and

a flow permeable membrane supported substantially on the first surface of the substrate and covering the electromagnetic effect field sensor.

2. The system of claim 1 wherein the flow permeable membrane is bonded to the electromagnetic effect field sensor by a layer of adhesive material.

3. The system of claim 1 further comprising a layer of material with low electrical conductivity interposed between the electromagnetic effect field sensor and the flow permeable membrane.

4. The system of claim 2 further comprising a layer of material with low electrical conductivity interposed between the adhesive layer and the electromagnetic effect field sensor.

5. The system of claim 1 wherein the electromagnetic effect field sensor detects an electromagnetic effect field emitted by a label in the flow permeable membrane.

6. The system of claim 1 wherein the flow permeable membrane further comprises:

passages for fluid to enter the membrane; and

features that divert fluid into proximity with the electromagnetic effect field sensor.

7. The system of claim 1 further comprising a backing structure in contact with a second surface of the substrate.

8. An electromagnetic effect system to detect labels in a fluid comprising:

at least one electromagnetic effect field sensor formed on a planar substrate and having a plurality of electrical terminations for communicating electrical signals responsive to the presence of electromagnetic effect fields;

a flow permeable membrane in proximity to the sensor;

an electromagnetic effect detection zone created in the permeable membrane by the proximity of the sensor;

a disposable assay cartridge comprising a housing, the electromagnetic effect field sensor and the flow permeable membrane; and

a first set of electrical interconnects formed on the surface of the housing and in electrical communication with the terminations on the electromagnetic effect field sensor.

9. The system of claim 8 further comprising:

a micro-controller based analysis circuit;

a system fixture containing the analysis circuit and a slot to receive the cartridge;

a second set of electrical interconnects within the slot and positioned to communicate electrically with the first electrical interconnects when the cartridge is within the slot.

10. The system of claim 9 wherein the second electrical interconnects are spring-loaded.

11. The system of claim 9 further comprising an electromagnetic effect field excitation source within the system fixture capable of generating an electromagnetic effect field at the electromagnetic effect field sensor when the cartridge is positioned within the slot of the system fixture.

12. A method for detecting the concentration of labels in a fluid comprising:

engaging a disposable electromagnetic field effect assay cartridge containing a flow permeable membrane and at least one electromagnetic effect field sensor with an analysis fixture;

producing an electromagnetic field effect detection zone in the flow permeable membrane with the electromagnetic effect field sensor;

flowing a fluid within the membrane and past the detection zone;

monitoring the output of the electromagnetic effect field sensor for a signal responsive to the presence of electromagnetic effect field labels in the fluid; and

relating the signal to an expected label concentration.

13. The method of claim 12 wherein the labels are concentrated in the label detection zone by selective binding of the labels to a label capture site disposed substantially within the label detection zone.

14. The method of claim 12 wherein the labels are partially excluded from the label detection zone by selective competitive unbinding of the labels to a label capture site disposed substantially within the label detection zone.

15. The method of claim 12 further comprising:

producing a second label detection zone in the assay cartridge with an electromagnetic effect field sensor;

flowing the sample past the second detection zone after the first detection zone;

monitoring the output of the second electromagnetic effect field sensor;

correlating the outputs of the first and second sensors to determine the flow rate of the sample within the membrane.