Search

EP-4737959-A2 - PHOTONIC INTERFEROMETER BASED SENSING

EP4737959A2EP 4737959 A2EP4737959 A2EP 4737959A2EP-4737959-A2

Abstract

A sensing system for characterizing analytes of interest in a sample is disclosed. It comprises a photonic integrated circuit with an integrated interferometer. The integrated interferometer is configured for spectroscopic operation. The integrated interferometer comprises at least a sensing arm and a reference arm, both the sensing arm and the reference arm having an exposable segment available for interaction with the sample, whereby the exposable segment of the reference arm has an optical path length which is smaller than twice the optical path length of the exposable segment of the sensing arm. The exposable section of the sensing arm is selective to the analyte of interest, whereas the exposable section of the reference arm is not selective to the analyte of interest.

Inventors

  • HOSTE, JAN-WILLEM

Assignees

  • MEEP BV

Dates

Publication Date
20260506
Application Date
20180901

Claims (11)

  1. A sensing system for characterizing analytes of interest in a sample, the sensing system comprising a photonic integrated circuit comprising an integrated asymmetric interferometer configured for spectroscopic operation, the integrated interferometer comprising exactly one sensing arm and exactly one reference arm of unequal length, both the sensing arm and the reference arm having an exposable segment available for interaction with the sample, whereby the exposable segment of the reference arm has an optical path length which is smaller than twice the optical path length of the exposable segment of the sensing arm, wherein the exposable segment of the sensing arm is selective to the analyte of interest, whereas the exposable segment of the reference arm is not selective to the analyte of interest, at least one of the sensing arm or the reference arm having a covered segment, not available for interaction with sample, wherein the length of the covered segment in the sensing arm is different from the length of the covered segment in the reference arm and wherein the overall optical path length difference between the reference and the sensing arm is such that the spectral transfer function of the interferometer has a period P and the system has a spectral resolution smaller than or equal to P/2.
  2. A sensing system according to claim 1, wherein the reference arm and the sensing arm both comprise a covered segment not interacting with the sample when the interferometer is in use.
  3. A sensing system according to any of the previous claims, wherein the interferometer is a Mach-Zehnder interferometer.
  4. A sensing system according to any of the previous claims, wherein only one of the sensing arm or the reference arm comprises a covered segment.
  5. A sensing system according to any of the previous claims, wherein the exposable segments that are exposed to the sample in the two arms, when the sensing system is in contact with the sample, have the same surface treatment finishing, except for the presence of active specific probes for probing analytes of interest.
  6. A sensing system according to any of the previous claims, wherein the radiation is guided in the photonic integrated circuit in waveguides, and wherein the width of waveguides in the covered segments in the reference arm and the sensing arm is substantially different and configured for a-thermal operation.
  7. A sensing system according to any of the previous claims, wherein the sensing system is free from active phase control elements or referencing electronics.
  8. A sensing system according to any of the previous claims wherein the sensing system comprises a radiation system for providing broadband radiation and/or a detector for detecting broadband radiation.
  9. A method for characterizing an analyte of interest in a sample, the method comprising - bringing the sample into contact with a sensing system according to any of the previous claims, - allowing, if present, analytes of interest to selectively bind to active probes in the exposable segment of the sensing arm, and - recording an optical interferogram in a spectroscopic way making use of said spectral transfer function for deriving therefrom a characteristic of the sample with respect to the analytes of interest.
  10. A method for characterizing according to claim 7, wherein the method comprises, for sensing analytes in a sample, a single fluidic interaction step with the sensing surface being the sample being brought in direct contact with the sensing surface.
  11. A method for characterizing according to any of claims 7 or 8 wherein the characteristic of the sample with respect to the analytes of interest is a presence or a quantity of the analyte of interest in the sample.

Description

Field of the invention The invention relates to the field of sensors. More specifically it relates to a system and method for sensing of analytes of interest based on specific binding events using a photonic, spectroscopic, interferometer for allowing high quality analysis. Background of the invention Label-free refractive index sensors designed for sensing purposes are inherently non-specific. Anything that changes the refractive index in the near vicinity of the sensor contributes to the signal. In order to make the sensor specific for a biomolecule such as a protein, the sensor is typically coated with a biochemical layer which only binds to the protein which needs to be detected. However, the refractive index can still change locally due to a change of fluid, change of temperature, a-specific binding, physical adsorption, strain, pressure, ionic loading of the surface, etc. This makes the use of these sensors challenging in an uncontrolled point-of-care environment, prone to changing environmental conditions and varying compositions of patient samples. One of the most-used self-tests for consumers is a pregnancy test. A major reason of its success is the ease-of-use: no manipulation is required except applying the sample. However, only lateral flow immunoassays such as a pregnancy test make this single-step use possible (dirty assay). Other more performant testing methods such as those used in clinical labs and in doctor's offices typically require several manipulation steps to perform the assay. In order to design a sensor system which is easy to use by non-trained personnel, as is the case in a consumer or a point-of-care setting, the number of manipulations has to be reduced to a minimum and the cost has to be several orders of magnitude lower than the professional systems. Ideally, a measurement can be done by just applying the sample without the need for applying different fluids or mixing the sample with reagents. This causes a problem for label-free sensors. Since these sensors respond to many different phenomena, they usually require a three-step protocol: first a baseline measurement with certain environmental conditions or with a certain liquid on top of the sensor, followed by flowing of the user sample and binding of the biomolecules to the sensor, and finally a return to the initial environmental conditions or a flow with the same liquid as the baseline measurement. This is necessary because it has to be guaranteed that a signal response can be allocated to the presence of the biomolecules, hence the environmental factors have to be kept constant as much as possible. This way, the status of the sensor (i.e. the spectrum or the intensity at a certain wavelength) is measured in step 3 and 1 and the difference is allocated to a certain concentration of biomolecules. A second reason for the last step is to wash off a-specifically bound or adsorbed molecules. A partial solution for the complexity of existing refractive index based sensing systems is suggested by Iqbal in IEEE J. Sel. Top. Quantum Electron. (2010) 654-661 by omitting the last washing step, reducing the number of fluidic steps from three to two. This is done by measuring the rate of change of the spectrum when the fluid switches from a buffer fluid to a buffer fluid containing the analyte. Nevertheless, this still requires a two-step process and only works in a lab environment when spiking a known fluid with an analyte, which can't be translated to a real-life situation of flowing human sample with unknown composition. When using an unknown patient sample, the slope of the binding curve would be obscured by a variety of phenomena happening simultaneously. Reducing the amount of fluidic steps thus requires reducing the response of the sensor to anything but the specific binding events. The problem of signal contributions not originating from specific binding is well-known and a known solution is to make use of a self-referencing system such as a symmetric Mach-Zehnder interferometer with monochromatic readout. The interferometer splits a wave in two or more components which each undergo a different path, before they are recombined. The difference in optical phase accumulated over the different paths is then transduced to an intensity change by a change in the interference pattern. The Mach-Zehnder interferometer thereby is particularly interesting for integrated photonics and low-cost sensing since it splits a waveguide in two arms and recombines the two waveguides to a single waveguide again which is coupled out of the chip. The interaction of the to-be-detected analytes with the Mach-Zehnder is restricted to one of the arms such that a phase change in the output can be allocated to the detection of the analytes. These Mach-Zehnder interferometers are typically read out in a monochromatic way. A detailed characterization thereof is done by Heideman and Lambeck in Sensors Actuators B Chem. (1999) 100-127. The configuration is a sym