(Differential) Refractive Index Measurement with low Uncertainties and Dimensions using an Asymmetric Nanofluidic Grating Detector


Sensors, Devices and Components

Ref.-No.: 0707-5502-BC

The invention relates to a new method for measuring the refractive index n of a substance with low uncertainties. The latter is in particular the case when the deviation of the refractive indices Δn, as compared to another substance, is only small (Δn < 0.02). Thereby, sensitive and contactless information on molecule concentration or process conditions for a wide range of applications can be obtained. The low uncertainties are enabled through the development of an asymmetric nanofluidic grating detector, which allows measuring the raw signal of the refractive index concomitant with direct background subtraction.

Fig. 1: Left: Cross-sectional schematic view of a single grating period. This grating reflects the incident coherent optical beam into several orders with an intensity profile that depends on the geometric parameters of the grating and on the refractive index of the fluid in the detection and reference nanochannels; Right: Schematic showing the nanofluidic diffraction grating with an asymmetric arrangement of detection and reference nanochannels. Open vias connect each nanochannel to the larger supply microchannels. [1]

Advantages

  • Direct classification of images
  • Reliable
  • Highly automated
  • Fully unsupervised operation possible
  • Does not rely on specific landmarks
  • Direct integration in OCT imaging devices possible
  • Allows a patient to know the level of progress of the disease

Applications

  • Concentration measurement
    • Dynamic (new n every minute)
    • Pure/particle free substances needed (300kDa cutoff filter)
    • Pressure driven fluidic system (up to 0.5 bar over pressure)

Technology

A schematic representation of the nanofluidic diffraction grating device, where reference and detection nanochannels are placed in an asymmetric interdigitating arrangement is shown in Fig. 1. The asymmetric unit cell of the grating results in the formation of a diffraction pattern which is not mirror-symmetric (I−m ≠ Im). Importantly, this asymmetric distribution is produced only when the refractive indices in the reference (yellow) and in the detection channels (green) are different Δn = nRef − nDet ≠ 0. This allows changes in the refractive index within the detection nanochannels to be detected by measuring the difference in intensity ΔIm = Im − Im. [2]

Background

Refractive index is a fundamental quantity, intrinsic to the physical and chemical properties of a substance. Measurements of refractive indices are widely used in the pharmaceutical industry, environmental monitoring, adulteration detection, and biosensing. Several technologies for refractive index measurement have been previously described in the literature, and with the push for further miniaturization, many microfluidic technologies have emerged.

Fig. 2: Setup of measurement

The observed diffraction pattern (cf. Fig. 1) is generated when the collimated laser beam in Fig. 2 (l=635 nm, waste diameter 360 µm) impinges on the nanofluidic grating and is then reflected back onto a mirror and into a CCD camera (Thorlabs DCU223M or Andor iXon Ultra) that records the intensity. The mirror is made out of a glass wafer with a reflecting gold layer on top. A slit (3 mm x 10 mm) in the centre of the mirror allows the incoming laser beam to pass, but the diffraction pattern is reflected towards the camera. Only the 0th maximum is not reflected as it also passes through the slit in the mirror. This is beneficial for the signal processing as the 0th maximum is very bright compared to the other maxima and might interfere with the other maxima without containing any information.

Publications

[1] Purr, F., Bassu, M., Lowe, R. D., Thürmann, B., Dietzel, A., & Burg, T. P. (2017). Asymmetric nanofluidic grating detector for differential refractive index measurement and biosensing. Lab on a Chip, 17(24), 4265–4272. https://doi.org/10.1039/C7LC00929A

Patent Infomation

[2] PCT (WO2019076994A1), EP, US, CN (application pending)

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