WO2021215925A1

WO2021215925A1 - Sensing device and sensing method

Info

Publication number: WO2021215925A1
Application number: PCT/NL2021/050266
Authority: WO
Inventors: Richard Alexander NORTE; Murali Krishna GHATKESAR
Original assignee: Technische Universiteit Delft
Priority date: 2020-04-22
Filing date: 2021-04-22
Publication date: 2021-10-28
Also published as: NL2025401B1

Abstract

The present disclosure relates to a method and apparatus for sensing of particles suspended in a fluid which flows through a channel, characterized in that a first optical element is attached to said channel; a second optical element is arranged near said first optical element; said first optical element and said second optical element have a photonic crystal structure; an optomechanical cavity is formed in the space between said first optical element and said second optical element; light is present in said optomechanical cavity; and said particles are sensed by reading out the optomechanical resonance of said light.

Description

SENSING DEVICE AND SENSING METHOD

The present disclosure relates to a device and method for sensing a property of a fluid in a vibratile microfluidic channel.

In chemical, environmental, biological, and medical research, as well as in industrial applications, it is desirable to be able to sense the presence of particles in fluids. Microfluidics is the discipline in which microscopic scale installations are used to sense the flow of particles through small channels. As examples, the mass, density, viscosity, flow rate, or mere presence of particles could be measured.

An important limiting factor in the measurement of particles in microfluidics is the precision of the measurement instrument.

Document US 2014/0051107 A1 describes a suspended microchannel resonator (SMR) to determine the relationship between a change in mass of the resonator caused by a change in the contents of its microchannel, for instance due to the presence of a particle. The change in mass is calculated from the resonance frequency shift of the suspended microchannel resonator (SMR) itself which shift is caused by the presence of the particle, the fluid density, and the particle density. The resonance frequency shift is measured by bringing the resonator into vibrational motion by applying a driving voltage signal to an electrode near the resonator and by sensing the change in the driving voltage signal caused by mass change in the resonator.

One known method of measuring in microfluidics involves running a channel over a microscopic scale cantilever; making a fluid which contains particles flow through the channel; shining a laser from a laser system on the cantilever; capturing the reflection of the laser light; and from this reflection deducing a change in a resonance of the cantilever which may happen in response to the passage of particles in the fluid.

A disadvantage of the abovementioned known method is that the initial alignment of the laser system with the channel is difficult and time-consuming. Another disadvantage is that the precision of the measurements is limited by the medium through which the laser light passes.

The method and apparatus described below provide improved sensing in order to at least partially address the abovementioned, and potentially other, disadvantages.

According to a first aspect a method of sensing at least one property of at least one of a fluid in a vibratile microfluidic channel and at least one particle in a fluid in a vibratile microfluidic channel, wherein the microfluidic channel is configured to cause the fluid to influence the vibration of the microfluidic channel, the method comprising:

- providing a first optical element arranged at or close to the vibratile microfluidic channel and a second optical element arranged near the first optical element, wherein the first optical element is configured to move along with the movement of the microfluidic channel and wherein an optomechanical cavity is formed between the first optical element and the second optical element and wherein vibration of the microfluidic channel causes a change in distance between the first optical element and second optical element;

- providing light into the optomechanical cavity by guiding light originating from a light source towards the second optical element and allowing light in the second optical element to be leaked into the optomechanical cavity to reflect between the first and second optical element, the changing distance between the first element and the second element forming the optomechanical cavity providing a changing mechanical resonance frequency associated with the vibration of the microfluidic channel;

- leaking light from the optomechanical cavity back to the second optical element;

- guiding light leaked back from the second optical element towards a photo detector and detecting light received by the photo detector;

- sensing the at least one property of the at least one of the fluid and the least one particle from a change of the mechanical resonance frequency determined from the light leaked into the second optical element and detected by the photo detector.

The property of the fluid may be at least one of the mass, density, viscosity and/or flow rate of the fluid, or (more specifically) at least one of the mass, density, viscosity, flow rate and/or presence of the at least one particle in the fluid.

The method may comprise: arranging a fluid containing at least one particle in the movable microfluidic channel, the fluid with the at least one particle causing motion of the microfluidic channel and the first optical element fixedly connected to or integrally formed with the microfluidic channel, wherein the motion of the microfluidic channel is changed relative to motion of the fluid channel without the presence of the at least one particle; providing light in the optomechanical cavity ; leaking light from the optomechanical cavity to the second optical element; sensing the at least one particle from a change of mechanical resonance frequency determined from the light leaked into the second optical element.

The method may comprise: determining from the light detected in the photo detector a change of the mechanical resonance frequency representative of the property of the fluid or the at least one particle in the fluid in the microfluidic channel, for instance the presence of the at least one particle in the microfluidic channel.

The types of said particles may include at least one of inorganic compounds, organic compounds, biomolecules, tissue samples, single proteins, viruses, cells, or micro-organisms. The sensing may be performed with a precision in the order of magnitude of 10 attogram, preferably a precision in the order of magnitude of one attogram or less.

The method may involve the use of laser light. Leaking of light into and/or from the optomechanical cavity may be accomplished through evanescent coupling. The method may be performed in an environment in a vacuum or at atmospheric pressure, wherein the vacuum has a pressure down to 10³ to 10¹⁰ mbar. In embodiments of the present disclosure the sensing device is arranged in a gas (for instance - but not limited to - air). The gas may be at atmospheric pressure or at low pressure (or even high vacuum or ultra high vacuum, for instance at pressures below 100 nanopascal) so that the gas does not dampen the motion of the channel or less so, thereby allowing an increased sensitivity of the sensor device. Preferably the sensing device is not submerged in liquid because the mechanical sensitivity of the sensing device may be damped by the liquid. However, a sensing device may be submerged in a liquid in case of any specific applications, for instance if the particles are larger than the channel size.

Sensing of the optomechanical resonance may comprise sensing at least one shift in at least one peak of said optomechanical resonance, wherein the frequency of the mechanical resonance is preferably between 1 kilohertz and 10 gigahertz.

The microfluidic channel may be brought into motion by (including the situation wherein the motion is changed of an already moving microfluidic channel, the existing movement being caused - for instance - by the flow of the fluid inside the microfluidic channel) the presence of the particle itself. In other embodiments the method comprises actively bringing the microfluidic channel and the first optical device into a background resonance state prior to sensing, for instance by making use of an actuator connected to the microfluidic channel and/or the first optical element.

According to another aspect a sensor device for sensing at least one property of a fluid in a vibratile microfluidic channel and at least one particle in a fluid in a microfluidic channel, the sensor device comprising: a vibratile microfluidic channel configured to allow the fluid or the at least one particle in the fluid inside the microfluidic channel to influence the vibration of the microfluidic channel; a first optical element arranged at or close to the vibratile microfluidic channel, the first optical element configured to move along with the movement of the microfluidic channel; a second optical element arranged near the first optical element, the first and second optical elements being spaced apart to form between them an optomechanical cavity; wherein the optomechanical cavity defines a mechanical resonance frequency associated with the vibration of the microfluidic channel; wherein the second optical element is configured to allow light present in the optomechanical cavity to leak into the second optical element; a light source for generating light; a photo detector for detecting light; a waveguide connected to the light source and photo detector and configured to guide light originating from the light source towards the second optical element and to guide light leaked into the optomechanical cavity from the second optical element, reflected inside the optomechanical cavity and leaked back from the optomechanical cavity into the second optical element towards the photo detector; a sensing unit connected to the photodetector and configured to determine from the light detected by the photodetector a change of mechanical resonance frequency determined from the light leaked into the second optical element.

In an embodiment the change of the mechanical resonance frequency determined by the sensing unit is representative of the properties of the fluid and/or the at least one particle in the fluid, for instance representative of the presence of the at least one particle in the microfluidic channel.

In embodiments of the present disclosure the first optical element is fixedly connected to or integrally formed with the vibratile microfluidic channel.

According to an embodiment the sensing unit is configured to sense from the light leaked into the second optical element a change of the mechanical resonance frequency representative of the change of the motion of the microfluidic channel resulting from the property of the fluid and/the at least one particle in the microfluidic channel.

According to an embodiment the sensor device comprises: a support configured to support at least one of the microfluidic channel and the first optical element, wherein the microfluidic channel is configured so that at least a part of the microfluidic channel is movable with respect to the support; a first optical element fixedly connected to or integrally formed with the movable microfluidic channel; a second optical element arranged near the first optical element.

In a further embodiment the first optical element comprises a first mirror surface and the second optical element comprises a second mirror surface facing the first mirror surface, the first mirror surface and second mirror surface being spaced apart to form between them an optomechanical cavity, wherein the optomechanical cavity defines a mechanical resonance frequency associated with the motion of the microfluidic channel.

In a further embodiment the sensor device comprises a waveguide connected to the light source and photo detector and configured to guide light originating from the light source towards the second optical element and to guide light leaked into the optomechanical cavity from the second optical element, reflected inside the optomechanical cavity and leaked back from the optomechanical cavity into the second optical element towards the photo detector.

According to an embodiment the second optical element comprises a first optical element part arranged near the first optical element and comprising the first mirror surface and a second optical element part arranged near the first optical element part and forming between them a further optical cavity, the first optical element part comprising a third mirror surface and the second optical element part forming a fourth mirror surface

According to an embodiment the sensor device comprises an actuator in connection with the microfluidic channel and configured to impose a vibration upon the microfluidic channel.

More specifically, the actuator may be able to actively bring the microfluidic device into a background resonance state prior to sensing.

According to an embodiment the first and second optical device, and optionally also at least a portion of the microfluidic channel, are implemented on a photonic crystal and/or the first and second optical device, optionally also at least a portion of the microfluidic channel, are formed by photonic crystals. The application of photonic crystals enable the sensor device to provide a nanophotonic readout. Such photonic crystal may comprise a periodic nanostructure enabling a waveguide configured for extremely low-loss waveguiding and/or the creation of an optomechanical cavity having highly reflective mirrors. The use of photonic crystals may assist in a cavity with small volume and a large bounce rate of the light within the volume, which in turn allows the sensing device to work at very low optical powers which is beneficial in view of energy consumption and increases sensitivity by reducing heating due to optical absorption. In general, photonic crystals are more sensitive to small movements and have higher optomechanical coupling, i.e. large measureable resonance frequency shifts even for small displacements in cavity.

According to another aspect of the present disclosure a sensing device is provided comprising an optical resonator with at least one movable part (i.e. the first optical element configured to move along with a microfluidic channel and/or second optical element) that changes its optical resonance. This optical resonator could be a zipper cavity where one or both of the two photonic crystal beams (forming the first and second optical element) are moveable.

According to an embodiment the second optical element is a static optical element.

According to an embodiment the second optical element is attached to a support element, preferably the support of the first optical element, and/or wherein the movable first optical element is configured to vibrate relative to the static second optical element.

According to an embodiment first and second optical elements, optionally also a portion of the microfluidic channel, are formed on one single integrated circuit. According to an embodiment sensing at least one particle comprises sensing at least one of the mass density, viscosity, flow rate, or presence of the at least one particle.

According to an embodiment the sensor device is configured to sense the mass of one particle with a precision in the order of magnitude of 10 attogram, preferably a precision in the order of magnitude of one attogram or less.

According to an embodiment the light source is light with a wavelength up to 2000 nm and/or light with a wavelength between 1500 nm and 1550 nm.

According to an embodiment the waveguide comprises a first waveguide arranged to carry light from the light source to the second optical element and a second waveguide, separate from the first wave guide and arranged to carry light from the second optical element to the photo detector. The waveguides can also be combined into a single, common waveguide.

According to an embodiment the waveguide comprises an optical fiber. In embodiments of the present disclosure the use of the optical fiber may make the alignment of the part of the sensing device (except of course the first and second optical elements) to be less critical.

According to an embodiment the second optical element is configured to allow laser light to exit the second optical element and to enter the optomechanical cavity through evanescent coupling and/or the second optical element is configured to allow laser light to exit from the optomechanical cavity to enter the second optical element through evanescent coupling.

According to an embodiment the sensor device is configured to sense the at least one particle using a Pound-Drever-Hah.

According to various embodiments the cross-section of the microfluidic channel is between 10 nm and 50 pm in size, optionally between 2 pm and 3 pm in size; and/or the flow rate in the microfluidic channel is in the order of magnitude of several femtoliters per second, optionally less than 5 femtoliters per second; and/or the thickness of walls of the microfluidic channel is between 5 nm and 7 pm; and/or the first optical element and second optical element have a length of the order of magnitude of several pm, optionally between 20 and 50 pm; and/or the first optical element and second optical element both have a width between 100 nm and 1500 nm; and/or the thicknesses of the first optical element and second optical element are between 20 nm and 2 pm; and/or the thickness of said first optical element and said second optical element is about 300 nm; and/or the optomechanical cavity is between 10 nm and 100 pm long and/or between 100 and 300 nm wide. According to an embodiment the sensor device is configured to sense at least one particle in an environment at a temperature between 0 and 100 degrees Celsius depending on the freezing and boiling points of the liquid in the microchannel.

According to an embodiment the sensor device is configured to sense the at least one particle in an environment at atmospheric pressure or at lower, for instance down to 10¹⁰ mbar.

According to an embodiment the sensing unit may be configured to determine at least one shift in at least one peak of said optomechanical resonance and/or wherein the frequency of the mechanical resonance is between 1 kilohertz and 10 gigahertz.

According to an embodiment the first optical element and second optical element are made of material having relatively low optical absorption and/or wherein made of a high- tensile material, optionally a tensile strength betweenl5 MPa and 10 GPa.

According to an embodiment the first optical element and second optical element are made partially or essentially fully of at least one of dielectric material such as silicon nitride (Si3N4), silicon carbide, or glass.

According to certain embodiments the first optical element and second optical element are made at least partially of at least one of c-Si, a-Si, Ges, GeSe, MoS2, SnS, MoSe2, GaAs, or diamond.

According to a further aspect an assembly is provided comprising a sensing device as defined herein and a vacuum chamber, wherein at least the movable part of the microfluidic channel, the movable first optical element and the second optical element are arranged in the vacuum chamber.

In the following description according to several figures several example of the method and sensing device will be described which may be used to sense various particles and properties thereof, the types of particles including at least one of inorganic compounds, organic compounds, biomolecules, tissue samples, single proteins, viruses, cells, or micro-organisms.

Using the method described below, and using a construction material with the appropriate properties, sensing may be performed with a precision down to attogram scale.

The method described below may be executed in an environment that is between 0 and 100 degrees Celsius. For instance the method may be executed at room temperature, more specifically between 18 and 25 degrees Celsius. Alternatively the method may be executed at body temperature, more specifically between 35 and 40 degrees Celsius. In these cases temperature control may not be required to execute the method. Execution at room temperature or at body temperature may be advantageous when working with biological matter, which in many cases may not tolerate deviations in temperature. Alternatively the method may be executed at much lower temperatures, and/or the temperature of the environment in which the method is used may be controlled. Examples of the method and sensing device apparatus will be described in detail by reference to the accompanying figures.

Figure 1 illustrates a first embodiment of a portion of a fluid channel coupled to an optical cavity.

Figure 2 illustrates another embodiment of a portion of a fluid channel coupled to an optical cavity.

Figures 3-6 show further embodiments of a portion of the sensing device.

Figure 7 illustrates an embodiment of the sensing device in a Pound-Drever-Hall measurement arrangement.

It is noted that, as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.

General outline

The present disclosure relates to a method and sensing device for sensing a property of at least a fluid in a vibratile microfluidic channel, for instance the presence or absence of a specific specimen of an extremely small particle, for instance a virus, protein or similar particles, in the fluid present in the microfluidic channel. The particle may be a particle moving through the channel or may be (quasi) stationary during the sensing interval. The particle present in the fluid(s), for instance may form a suspension or emulsion, may be mixed with or solved in the fluid, etc. The method and device may be configured to sense at least one of the mass, density, viscosity, flow rate, or presence of the at least one particle (i.e. one particle or a set of particles).

In embodiments of the present disclosure, the sensing device and method make use of an optomechanical cavity arranged between a first mirror surface formed by a movable first optical element and a second mirror surface formed by a static second optical element. It is to be noted here that the term "mirror surface" used throughout the present specification refers to the property of light reflectivity of the specific side of the optical element. The term is generally intended to refer to the properties of the optical element itself rather than to specific mirror like layers or similar structures provided at the side of the optical element. The reflectivity can be accomplished in various ways, for instance by the selecting an appropriate material and composition of the optical element, as will be appreciated by the person skilled in the art of optics.

The static second optical element may be attached to a support structure and is kept stationary. The microfluidic channel and the first optical element attached thereto or formed therewith may be connected to the same or to a different support structure in such a manner (for instance, the microfluidic channel may be suspended from the support structure, for instance forming a cantilever structure) that the microfluidic channel and first optical element are movable with respect to its support structure (and to the second optical element).

In some embodiments the mirror surfaces are essentially flat surfaces aligned relative to each other, i.e. the first mirror surface is arranged to extend generally parallel to the second mirror surface. In other embodiments the optical elements may have curved mirror surfaces, for instance concentric (spherical) mirror surfaces, confocal mirror surfaces, hemispherical mirror surfaces or concave -convex mirror surface.

Light from a light source optically coupled to the second optical element travels towards the second optical element and may partially leak into the optomechanical cavity. The light leaked into the optical cavity is reflected inside the optical cavity. A part of the reflected light may leak back into the second optical element. This part of the light leaked back into the second optical element travels in opposite direction from the second optical element and is detected by a light sensor, herein also referred to as a photo detector.

The optical elements on both sides of the optomechanical cavity are arranged to allow any light entering the cavity because of leakage of light from the second optical element, to be trapped inside the cavity and to reflect between the mirrors of the optomechanical cavity a large number of times. The reflections produce standing waves at certain resonance frequencies.

More generally, the optomechanical cavity is used to enhance the pressure interaction between light (i.e. photons) and matter. Photons reflecting off a mirror surface of an optical element transfers momentum onto the mirror surface due to the conservation of momentum. The transfer of momentum may become significant since the mass of both optical elements is very small, the number of photons leaking into the cavity is relatively large (especially in cases wherein the light source is a laser light source in view of the relatively large light intensity of the laser light) and because of the arrangement of the mirror surfaces the photons in the cavity bounce off the mirror surfaces a large number of times (each time a photon hits a mirror surface momentum is transferred to the optical element). The vibrating (oscillating) first optical element causes a modulation (i.e. a variation) of the width of the optomechanical cavity, which modulation can be directly seen in the spectrum of the optomechanical cavity. When one or more particles pass through the microfluidic channel, the mass of the one or more particles causes the microfluidic channel and therefore also the first optical device connected to the microfluidic channel or integrally formed therewith, to move. In embodiments of the present disclosure the microfluidic channel is brought into motion by an external actuator. When the microfluidic channel is brought into motion by an external actuator, a vibration may be imposed onto the movable first optical device. The presence of the one or more particles in the microfluidic channel may influence the imposed vibration. In other embodiments wherein the microfluidic channel is not brought into motion by an external actuator, the (flow of the fluid may result in a vibrational motion of the microfluidic channel and the) passing of the one or more particles through the microfluidic channel may itself cause the microfluidic channel and first optical element directly or indirectly connected thereto or integrally formed therewith to be brought into a (changed) vibrating motion as well. More specifically, in both cases the mass of the one or more particles will change (i.e. shift) the mechanical resonance frequency of the movable first optical element. The change or shift of the mechanical resonance frequency of the first optical element may be measured with ultra-high precision by using the measurement arrangement comprising the optomechanical cavity formed between the movable first optical element and the second optical element.

Exemplifying embodiments

Referring to figure 1 an embodiment of a portion of a sensing device 1 is depicted. The figure shows a microfluidic channel 10. The microfluidic channel is configured so that it may vibrate. The vibration can be actively generated, for instance by a motion actuator 19 provided at one end of the microfluidic channel 10, or may the result of the presence (for instance the flow) of the fluid inside the channel 10 (wherein the fluid may be a liquid, a gas or a mixture of liquid and gas, and wherein the fluid may or may not comprise one or more particles P, like biomolecules, tissue samples, single proteins, viruses, cells, micro-organisms and/or particles of inorganic compounds or organic compounds). A first optical element 2 is arranged at or close to the vibratile microfluidic channel 10, while a second optical element 3 is arranged near the first optical element. The microfluidic channel 10, first optical element 2 and second optical element may be essentially parallel to each other. An optomechanical cavity 7 is formed between the first optical element 2 and the second optical element 3. The first optical element 2 is either directly or indirectly coupled to the microfluidic channel 10 so that movement (vibration, for instance in directions P_L) of the microfluidic channel 10 causes a movement of the first optical element 2 as well (directions P₂, figure 1). In case of indirect coupling the first optical element 2 may be freestanding relative to the microfluidic channel 10 as is shown in figure 1. In case of direct coupling (cf. the embodiment of figure 2, for instance) the first optical element may be fixedly connected to or integrally formed with the microfluidic channel 10.

Vibration of the microchannel 10 causes variation of the distance between the first and second optical elements 2,3 and therefore variation of the width of the optomechanical cavity 7. This variation of the width of the optomechanical cavity 7 may be sensed in the following manner. Light from a light source 5 may be guided through an arbitrarily shaped waveguide 4 to an area close the second optical element 3 and therefore close to the optomechanical cavity. Light from the waveguide 4 may be leaked into the second optical element 2 (direction P₃, cf. figure 1) and light from the second optical element 3 may be leaked into the optomechanical cavity 7. Inside the optomechanical cavity 7 the light will reflect in opposite directions (P₄), causing resonance at certain frequencies. A part of the light inside the optomechanical cavity 7 will leak back into the second optical element 2 (direction P₅) and can be detected by a light detecting unit 6 connected to the waveguide 4. Changes in vibration characteristics of the microfluidic channel 10 caused by properties of the fluid (liquid and/or gas), with or without the presence of particles P, will be passed to the vibration of the first optical element 2 and therefore will result in corresponding changes in the width of the optomechanical cavity 7 and therefore in shift of the resonance frequency or frequencies (and possibly also the value of the intensity of the light at the resonance frequencies) of the light resonating inside the optomechanical cavity 7. This change of resonance frequencies can be detected by the light detecting unit 6. The light detecting unit 6 then may generate an output signal representative of the properties of the fluid or particles inside the microfluidic channel.

Referring to figure 2 another embodiment of a portion of a sensing device 1 is depicted. The figure shows a microfluidic channel 10 similar to the microfluidic channel of figure 1. The cross-section of the microfluidic channel 10, in case of a circular diameter the diameter (d, figure 1) of the microfluidic channel 10 may in the range of 10 nm to 50 pm, optionally between 2 and 3 pm. In the shown embodiment a first optical element 12 is integrally formed with the wall 11 of the channel 10. In other embodiments (not shown) the first optical element 12 may be a separate element that is fixedly attached to the wall 11 of the channel 10. In all these embodiments any movement of the microfluidic channel 10, like a vibration of the channel wall 11 in the transversal direction (T, cf. figure 2 wherein the figure shows the first optical element 12 (solid lines) in a left most position, the first optical element 12 (dotted lines) in a right-most position and an imaginary center line 22 between both positions ) will be directly imparted on the first optical element 12. In other words, the first optical element co-moves with the movement of the channel wall 11.

The microfluidic channel 10 may be a freestanding channel connected to a support (not shown in the drawing), may be connected as a cantilever to the support or in a similar manner arranged in the sensing device 1. Inside the microfluidic channel a single particle (P) is traveling past the first optical element 12. The presence of the particle (P) inside the channel 10 influences the vibration characteristics of the channel 10 and the movable first element 12. In the figure an optional actuator 19 is schematically shown. The actuator 19 may be configured to bring the microfluidic channel 10 into a vibrational motion.

Spaced apart and extending generally in an axial direction parallel to the first optical element 12 a second optical element 13 is arranged. The second optical element may be a static element that has been attached to a support element, for instance the support of the first optical element or another support element . Furthermore, the first optical element 12 has a (first) mirror surface 14 facing the second optical element 13, while the second optical element 13 has a (second) mirror surface 15 facing the first optical element 12. In the shown embodiment the mirror surfaces 14 and 15 are concave mirror surfaces and the average width (W) between (the center of) both mirror surfaces 14,15 is relatively small, typically between between 100 nm and 300 nm wide. Between the mirror surfaces 14,15 an optomechanical cavity 20 is defined. Light that has leaked into this cavity 20 is reflected back and forth between the first and second optical element 12,12, as is indicated schematically by reference number 21.

Light may be present in the optical cavity 20. In some embodiments the cavity 20 is not optically shielded at the sides of the cavity which are not blocked by the optical elements 12,13 (in figure 2, the upper and lower sides of the cavity are unshielded and in fact open. However, the leakage of light from the cavity 20 is still limited.

As the particle (P) moves through the channel 10, the passage of the particle’s mass may make the channel 10 vibrate (or may change the vibration the channel already has as a result of the actuator 19). This vibration may induce a mechanical resonance into the optical element 102. This mechanical resonance may affect the resonance of the light in the optical cavity 20, as is explained hereafter.

Figure 2 schematically shows a first wave guide 26 connected to a light source 28 (only shown schematically)configured to generate light and send the light through the waveguide 26 towards the second optical element 13. Light in the second optical element 13 then leaks to some extent into the optomechanical cavity 20. The light in the optomechanical cavity 20 is then caused to reflect between the (mirrors 14,15 of the) first and second optical element 12,13. A part of the light reflected between the first and second optical element 12,13 eventually is leaked back into the second optical element 13 and then transported through a second waveguide 27 to a photodetector 29 (only shown schematically). In other embodiments (shown hereafter) the first and second waveguides 26,27 have been combined into one waveguide. In any case suitable optical elements such as beam splitters may be connected to the sensing device 1 to ensure that the incoming and outgoing light is traveling in the correct directions. Based on the light leaked back from the second optical element 13 and detected by the photo detector 29, a sensing unit 30 determines from the light detected in the photo detector 29 a change of the mechanical resonance frequency representative of the presence of the at least one particle in the microfluidic channel 10.

The embodiment shown in figure 3 is similar to the embodiment of figure 2. The second optical element 13 comprises in this embodiment a first optical element part 32 arranged near the first optical element 12 and comprising the first mirror surface 15 and a second optical element part 33 arranged near the first optical element part 33 and forming between them a further optical cavity, the first optical element part 32 comprising a third mirror surface 35 and the second optical element part forming a fourth mirror surface 36. Instead of guiding the light leaked back from the cavity 20 into the second element 13 through a waveguide 27, the light is leaking through the second cavity 31 towards the first optical element part 33 and then (cf. 40) towards the photodetector 29 and sensing unit 30 (not shown for easy of drawing).

Figure 3 also shows a graph 41 indicating the light intensity (I) as function of frequency (to) for the situation without the presence of the particle P inside the microfluidic channel 10 (in dotted line 42) and the situation with the particle P present inside the microfluidic channel 10 (solid line 43). More specifically, the resonance peak in the sensed intensity is changed, i.e. shifted, to the right (over frequency interval 44). Due to the presence of the shift of the mechanical resonance frequency (i.e. the resonance peaks shown in the graph) of the movable first optical element 12 and the ultra-high precision read-out de using the optical cavity / cavities, the sensing unit 30 is able to determine a change of the mechanical resonance frequency representative of the presence of the at least one particle in the microfluidic channel. The sensing unit 30 then may generate a sensing unit output signal 45 (figure 2) that is representative of the presence (or absence) of the particle in the microfluidic channel 10.

The observation that there is a shift in resonance frequency may lead to the conclusion that a particle is passing the first optical element. Furthermore, the mass of the particle can be determined from the value of the resonance frequency shift. In general, a large shift denotes a large mass while a small shift indicates a small mass.

Figure 4 illustrates an example wherein (at least) a first optical element 50 and a second optical element 51 are embodied as a photonic crystal. Figure 4 only shows the arrangement of the microfluidic channel 10, the first optical element 50 and the second optical element 51. The second optical element 51 can be connected to one or more waveguides, a light source, a photodetector and a sensing unit as is indicated in connection with figures 2 and 3. Additionally, the fluid channel 10 may be attached at one end to a support (like a cantilever) so as to facilitate its vibration. The fluid channel and/or the attached optical first element 50 may be excited by an actuator, that is, brought into a background vibration state, or in other words a background resonance state or background resonance mode, prior to the execution of the method of sensing

In the embodiment of figure 4 the second element 51 is made from a material that allows light to leak out of the second optical element 51 towards the cavity 52 and from the cavity 52 towards the second optical element 51. The first and second optical elements 50, 51 comprise reflecting surfaces 53, 54, respectively, so as to form the optomechanical cavity 52.

Furthermore, the fluid channel 10 and the optical elements 12, 13, 32, 33, 50, 51 may be made of a high-tensile or in other words high-strain construction material. The two optical elements may be beams, which may be constructed from a film of the construction material. The high-tensile construction material may be utilized in order to provide sufficient tensile strength to reduce noise in the mechanical resonance so as to make optimal use of the potential sensitivity of the method. A mechanical resonance of the fluid channel and/or the optical elements may vary substantially and may be between 1 kilohertz and 1 gigahertz, or even between 1 kilohertz and 10 gigahertz.

As mentioned above, the optical elements 50, 51 may have a photonic crystal structure. The optical elements 50, 51 may have a length of between 20 and 50 pm, a width of between 500 nanometers and 1500 nanometers, and a thickness of between 20 nanometers and 2 pm, preferably 300 nanometers. The optical cavity 20, 31, 52 may be a nanocavity, that is, a cavity with nanoscale dimension. More specifically the optical cavity may have a width of between 10 nanometers and 2 pm, and more preferably between 100 and 300 nanometers wide.

The optical cavity with a photonic crystal structure may more specifically be an optomechanical cavity, in which the mechanical resonance and the optical resonance are coupled to each other to form a combined optomechanical resonance. An optomechanical resonance may have an optomechanical resonance distribution in which one or more peaks may be detected according to the presence or passage of particles in the microfluidic channel.

Figure 5 illustrates an embodiment similar to the embodiment of figure 3, wherein the fist and second optical elements 69, 61 are embodied in a photonic crystal. The second optical element 61 comprises a first optical element part 66 and a second optical element part 67. The waveguide 63 may be comprised of an optical fiber, for example. That is, the light may be shuttled to the cavity 68 between the first optical element 69 and the second optical element 61 through fiber optics. The optical element part 67 may be a beam and it may have a photonic crystal structure as well.

The optical coupling may comprise evanescent coupling, which may be described as an optical phenomenon in which some of light leaks from the third optical element into the cavity and from the cavity back to the third optical element. Evanescent coupling may be the mechanism through which light enters or is input into the optical cavity 68, and/or evanescent coupling may be the mechanism through which light exits the optical cavity.

Alternatively the input/output element 63 may consist of a waveguide only, where the waveguide is an optical fiber which input, in other words shuttles, the light directly into the optical cavity, or where the waveguide takes some other form.

The light input into the optical cavity through the input/output element may be laser light, which may have a wavelength of up to 2000 nanometers, for example light in the visible spectrum, for example light with a wavelength of 500 nanometers, or for example light in the near infrared or infrared spectrum, for example light with a wavelength between 1500 and 1550 nanometers.

Figure 6 illustrates a side-view of an example of sensing device G. The core elements outlined above, being the channel, optical elements and/or input-output element may be constructed on the same single microchip 70. These elements may attached to the microchip through structural elements with a specifically designed shape, or they may be attached substantially directly to the microchip.

These core elements may be manufactured out of the same piece of material in the same manufacturing process as a single integrated circuit. Manufacturing these core elements out of the same piece of material in the same process may substantially ease production and may obviate the need for an alignment step of various elements at the moment when the system is set up.

The microchip 70 may be supported by a piezoelectric element 71 which isolates the microchip and/or keeps the state of the microchip with regard to electric effects constant. The microchip and/or the piezoelectric element may be supported by a support element 72.

The fluid which may contain the particles may be input into the channel and output from the channel by microfluidic input and output elements 504 which may be attached to the microchip substantially in a plane with the core elements or which may be attached at an angle to the microchip. The angle may be such as to optimize the flow of the fluid in order to support the sensing method. The angle of the microfluidic input and output elements 73 may be adjustable.

The core elements may be present in an uncontrolled atmosphere being at substantially atmospheric pressure, or the core elements may be more preferably present in a controlled atmosphere, preferably substantially a vacuum. For example, a substantial vacuum could mean an environment with a pressure of down to 10¹⁰ bar. One reason why operating in a vacuum could be preferable is to optimize the sensitivity of the method.

The light 74 input and output from the core elements is supplied by the arrangement of figure 7. The figure shows a typical Pound-Drever-Hall measurement setup. The setup comprises a laser source 81, a first beam splitter 82, a wave-meter 83, a modulator 84 for example an electro optic modulator, a beam direction element 85 for example a second, polarizing beam splitter or a circulator, a photodetector 86, a computer 87, an oscillator 88, for example an RF oscillator, and a mixer 89. The laser source 81 may produce laser light which may pass through a first beam splitter 82 where part of the light is directed toward the wave-meter 83 in order to aid in controlling a potential error of the laser source. The laser light may pass through a phase modulator 84 or may be modulated in the laser source 81. The laser light is directed through a beam direction element 85 toward the core elements (not shown).

Returning light is directed by the beam direction element 85 toward the photodetector 86. The photodetector senses the returning light and is connected to the computer via the computer connection 87 for data acquisition.

An oscillator 88 and a mixer 89 may be used to aid in modifying the laser light, for example by impressing side bands onto the laser light. The modification of the laser light may aid in matching phases or other properties of the outwardly directed light and the returning light, in order to aid in acquiring more precise data and/or in order to aid in controlling the laser source.

The Pound-Drever-Hall measurement setup system may measure or may enable a computer and/or software system to measure and/or display peaks in the frequency distribution of the exiting light. More specifically this measurement may comprise sensing at least one shift in at least one peak of the optomechanical resonance distribution.

Constructing the optical elements from any of the indicated materials may improve the sensing capabilities of the sensing device. Various materials are considered with various properties, being mass density, absorption coefficient and refractive index. A particularly useful material is silicon nitride (Si₃N₄). The construction material may alternatively be c-Si, a-Si, Ges, GeSe, MoS₂, SnS, MoSe₂, GaAs, and diamond. The construction material may also alternatively be a form of glass or silicon carbide.

It may be derived that the preferred refractive index, the mass density, and the absorption of any of the materials should be in the range of 5.5 - 1.5, 2 - 7 g cm³ and 0.002-1.000 cm¹, respectively.

The mass density of the construction material influences its oscillation or in other words its resonance properties. The tensile strength of the construction material also influences its oscillation or in other words resonance properties. The core elements, especially the optical elements, may be made out of a high-tensile material with strength between 15 MPa and 10 GPa. A high tensile strength of the construction material will improve the sensitivity of the sensing of the core elements.

The refractive index of the construction material influences its ability to trap light. The value of the refractive index may be optimized according to various trade-offs. A construction material with a high refractive index will trap light more easily and will allow the cavity to contain light better and so to work better. On the other hand, core elements made out of a construction material with a high refractive index may overheat faster. The absorption coefficient of the construction material may also be optimized according to various trade-offs.

It is to be understood that this invention is not limited to particular aspects described, and, as such, may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

Claims

1. Method of sensing at least one property of at least one of a fluid in a vibratile microfluidic channel and at least one particle in a fluid in a vibratile microfluidic channel, wherein the microfluidic channel is configured to cause the fluid to influence the vibration of the microfluidic channel, the method comprising:

2. Method as claimed in claim 1 wherein sensing the at least one property comprises determining from the light detected in the photo detector a change of the mechanical resonance frequency representative of the property of the fluid or the at least one particle in the fluid in the microfluidic channel, for instance the presence of the at least one particle in the microfluidic channel.

3. Method as claimed in claim 1 or 2, wherein sensing the at least one property comprises at least one of sensing the mass, density, viscosity, flow rate and/or presence of the at least one particle in the fluid and sensing the mass, density, viscosity and/or flow rate of the fluid itself.

4. Method as claimed in claim 1, 2 or 3, wherein the first optical element is a movable optical element that is fixedly connected to or integrally formed with the microfluidic channel.

5. Method as claimed in any of the preceding claims, wherein the second optical element is freestanding from the first optical element and/or wherein the second optical element is a static optical element.

6. Method as claimed in any of the preceding claims, comprising: arranging a fluid containing at least one particle in the movable microfluidic channel, the fluid with the at least one particle causing motion of the microfluidic channel and the first optical element fixedly connected to or integrally formed with the microfluidic channel, wherein the motion of the microfluidic channel is changed relative to motion of the fluid channel without the presence of the at least one particle; providing light in the optomechanical cavity ; leaking light from the optomechanical cavity to the second optical element; sensing the at least one particle from a change of mechanical resonance frequency determined from the light leaked into the second optical element.

7. Method as claimed in any of the preceding claims, wherein the types of said particles include at least one of inorganic compounds, organic compounds, biomolecules, tissue samples, single proteins, viruses, cells, or micro-organisms.

8. Method according to any of the preceding claims, wherein sensing is performed with a precision in the order of magnitude of 10 attogram, preferably a precision in the order of magnitude of one attogram or less.

9. Method according to any of the previous claims, wherein said light comprises laser light.

10. Method according to any of the preceding claims, wherein leaking of light into and/or from the optomechanical cavity is accomplished through evanescent coupling.

11. Method according to any of the previous claims, wherein the method is performed in an environment in a vacuum or at atmospheric pressure, wherein the vacuum has a pressure down to 10¹⁰ mbar.

12. Method according to any of the previous claims, wherein said sensing of said optomechanical resonance comprises sensing at least one shift in at least one peak of said optomechanical resonance, wherein the frequency of the mechanical resonance is preferably between 1 kilohertz and 10 gigahertz.

13. Method according to any of the previous claims, comprising actively bringing the microfluidic channel and the first optical device into a background resonance state prior to sensing.

14. Method as claimed in any of the preceding claims, wherein the first optical element is either directly or indirectly coupled to the microfluidic channel.

15. Method as claimed in claim 14, wherein a directly coupled first optical element and microfluidic channel comprises a first optical element fixedly connected to or integrally formed with the microfluidic channel.

16. Sensor device for sensing at least one property of at least one of a fluid in a vibratile microfluidic channel and at least one particle in a fluid in a vibratile microfluidic channel, the sensor device comprising: a vibratile microfluidic channel configured to allow the fluid or the at least one particle in the fluid inside the microfluidic channel to influence the vibration of the microfluidic channel; a first optical element arranged at or close to the vibratile microfluidic channel, the first optical element configured to move along with the movement of the microfluidic channel; a second optical element arranged near the first optical element, the first and second optical elements being spaced apart to form between them an optomechanical cavity; wherein the optomechanical cavity defines a mechanical resonance frequency associated with the vibration of the microfluidic channel; wherein the second optical element is configured to allow light present in the optomechanical cavity to leak into the second optical element; a light source for generating light; a photo detector for detecting light; a waveguide connected to the light source and photo detector and configured to guide light originating from the light source towards the second optical element and to guide light leaked into the optomechanical cavity from the second optical element, reflected inside the optomechanical cavity and leaked back from the optomechanical cavity into the second optical element towards the photo detector; a sensing unit connected to the photodetector and configured to determine from the light detected by the photodetector a change of mechanical resonance frequency determined from the light leaked into the second optical element.

17. Sensor device as claimed in claim 16, wherein the change of the mechanical resonance frequency determined by the sensing unit is representative of the properties of the fluid and/or the at least one particle in the fluid, for instance representative of the presence of the at least one particle in the microfluidic channel.

18. Sensor device as claimed in claim 16 or 17, wherein the first optical element is a movable optical element that is fixedly connected to or integrally formed with the vibratile microfluidic channel.

19. Sensor device as claimed in any of claims 16-18, comprising: a support configured to support at least one of the microfluidic channel and the first optical element, wherein the microfluidic channel is configured so that at least a part of the microfluidic channel is movable with respect to the support; a first optical element fixedly connected to or integrally formed with the movable microfluidic channel; a second optical element arranged near the first optical element; wherein, optionally, the first optical element comprises a first mirror surface and the second optical element comprises a second mirror surface facing the first mirror surface, the first mirror surface and second mirror surface being spaced apart to form between them an optomechanical cavity, wherein the optomechanical cavity defines a mechanical resonance frequency associated with the motion of the microfluidic channel;

20. Sensor device as claimed in any of the claims 16-19, wherein the second optical element comprises a first optical element part arranged near the first optical element and comprising the first mirror surface and a second optical element part arranged near the first optical element part and forming between them a further optical cavity, the first optical element part comprising a third mirror surface and the second optical element part forming a fourth mirror surface

21. Sensor device as claimed in any of claims 16-20, comprising an actuator in connection with the microfluidic channel and configured to impose a vibration upon the microfluidic channel.

22. Sensor device as claimed in any of claims 16-21, wherein the first and second optical device, and optionally also at least a portion of the microfluidic channel, are implemented on a photonic crystal and/or wherein the first and second optical device, optionally also at least a portion of the microfluidic channel, are formed by photonic crystals.

23. Sensor device as claimed in any of claims 16-22, wherein the second optical element is a static optical element.

24. Sensor device as claimed in any of the claims 16-23, wherein the second optical element is attached to a support element, optionally a support of the first optical element, and/or wherein the movable first optical element is configured to vibrate relative to a static second optical element.

25. Sensor device as claimed in any of claims 16-24, wherein first and second optical elements, optionally also a portion of the microfluidic channel, are formed on one single integrated circuit.

26. Sensor device as claimed in any of claims 16-25, configured to sense the mass of one particle with a precision in the order of magnitude of 10 attogram, preferably a precision in the order of magnitude of one attogram or less.

27. Sensor device as claimed in any of claims 16-26, wherein the light source is a source of laser light or a laser light source for generating visible light and/or laser light, respectively.

28. Sensor device as claimed in any of claims 16-27, wherein the light source is light with a wavelength up to 2.000 nm and/or light with a wavelength between 1500 nm and 1550 nm.

29. Sensor device as claimed in any of claims 16-28, wherein the waveguide comprises a first waveguide arranged to carry light from the light source to the second optical element and a second waveguide, separate from the first wave guide and arranged to carry light from the second optical element to the photo detector.

30. Sensor device as claimed in any of claims 16-29, wherein the waveguide comprises an optical fiber.

31. Sensor device as claimed in any of claims 16-30, wherein the second optical element is configured to allow laser light to exit the second optical element and to enter the optomechanical cavity through evanescent coupling and/or wherein the second optical element is configured to allow laser light to exit from the optomechanical cavity to enter the second optical element through evanescent coupling.

32. Sensor device as claimed in any of claims 16-31, configured to sense the at least one particle using a Pound-Drever-Hall unit.

33. Sensor device as claimed in any of claims 16-32, wherein: the cross-section of the microfluidic channel is between 10 nm and 50 pm in size, optionally between 2 pm and 3 pm in size; and/or the flow rate in the microfluidic channel is in the order of magnitude of several femtoliters per second, optionally less than 5 femtoliters per second; and/or the thickness of walls of the microfluidic channel is between 5 nm and 7 pm; and/or the first optical element and second optical element have a length of the order of magnitude of several pm, optionally between 20 pm and 50 pm; and/or the first optical element and second optical element both have a width between 500 nm and 1.500 nm; and/or the thicknesses of the first optical element and second optical element are between 20 nm and 2 pm; and/or the thickness of said first optical element and said second optical element is about 300 nm; and/or the optomechanical cavity is between 10 nm and 2 pm long and/or between 100 and 300 nm wide.

34. Sensor device as claimed in any of claims 16-33, configured to sense the at least one particle in an environment at a temperature between 0 and 100 degrees Celsius, preferably between 18 and 25 degrees Celsius or in an environment between 35 and 40 degrees Celsius.

35. Sensor device as claimed in any of claims 16-34, configured to sense the property in an environment at atmospheric pressure or at lower, preferably at a high vacuum pressure or lower.

36. Sensor device as claimed in any of claims 16-35, wherein the sensing unit is configured determine at least one shift in at least one peak of said optomechanical resonance and/or wherein the frequency of the mechanical resonance is between 1 kilohertz and 10 gigahertz.

37. Sensor device as claimed in any of claims 16-36, wherein the optomechanical cavity is essentially unshielded at the sides of the cavity that are not blocked by the first and second optical elements.

38. Sensor device as claimed in any of claims 16-37, wherein the first optical element and said second optical element are made of material having relatively low optical absorption and/or wherein made of a high-tensile material, optionally a tensile strength between 15 MPa and 10 GPa.

39. Sensor device as claimed in any of claims 16-38, wherein the first optical element and second optical element are made partially or essentially fully of at least one of silicon nitride (Si3N4), silicon carbide, or glass.

40. Sensor device as claimed in any of claims 16-39, wherein the first optical element and second optical element are made at least partially of at least one of c-Si, a-Si, Ges, GeSe, MoS2, SnS, MoSe2, GaAs, or diamond.

41. Sensor device as claimed in any of claims 16-40, wherein the device is configured to apply the method according to any of claims 1-15.

42. Sensor device as claimed in any of the claims 16-41, wherein the first optical element is either directly or indirectly coupled to the microfluidic channel.

43. Sensor device as claimed in claim 42, wherein a directly coupled first optical element and microfluidic channel comprises a first optical element fixedly connected to or integrally formed with the microfluidic channel.

44. Assembly of a sensor device as claimed in any of claims 16-43 and a vacuum chamber, wherein at least the movable part of the microfluidic channel, the first optical element and the second optical element are arranged in the vacuum chamber.