WO2022019919A1

WO2022019919A1 - Plasmonic sensors with microfluidic channels

Info

Publication number: WO2022019919A1
Application number: PCT/US2020/043441
Authority: WO
Inventors: Fausto D'APUZZO; Steven Barcelo; Viktor Shkolnikov
Original assignee: Hewlett Packard Development Co LP
Current assignee: Hewlett Packard Development Co LP
Priority date: 2020-07-24
Filing date: 2020-07-24
Publication date: 2022-01-27
Anticipated expiration: 2023-01-24

Abstract

In example implementations, a sensor is provided. The sensor includes a plasmonic sensor formed on a substrate. A first set of microfluidic channels and a second set of microfluidic channels are located over the plasmonic sensor. A first fluid source is to provide a first fluid to flow through the first set of microfluidic channels and over the plasmonic sensor. A second fluid source is to provide a second fluid to flow through the second set of microfluidic channels and over the plasmonic sensor. A clear capping layer is formed over the first set of microfluidic channels and the second set of microfluidic channels.

Description

PLASMONIC SENSORS WITH MICROFLUIDIC CHANNELS

BACKGROUND

[0001] Sensors can be used to detect the presence of certain analytes and compounds in a fluid. The sensors can also be used to measure a concentration of a particular analyte. Some sensors may be plasmonic sensors that are based on surface-enhanced spectroscopies (SER) or surface plasmon resonances (SPR).

[0002] SER based sensors can use nanogaps between metal nanostructures or sharp features of single nanostructures that can produce high electromagnetic field enhancements under resonant excitation. SPR based sensors are based on a resonant peak shift of surface plasmons due to the change of the refractive index of the surrounding environment. The molecules adsorbed on the surface of metal nanostructures may have different refractive indices from the surrounding medium. The amount of peak shift per refractive index unit change may be defined as the sensitivity to characterize the performance of a SPR based sensor.

BRIEF DESCRIPTION OF THE DRAWINGS [0003] FIG. 1 illustrates a block diagram of a sensing apparatus with a plasmonic sensor of the present disclosure;

[0004] FIG. 2 illustrates different examples of multi-line illumination components of the sensing apparatus;

[0005] FIG. 3 illustrates a top view of an example of the plasmonic sensor of the present disclosure;

[0006] FIG. 4 illustrates a cross-sectional side view of an example of the plasmonic sensor of the present disclosure;

[0007] FIG. 5 illustrates different cross-sectional views of different examples of the plasmonic sensor of the present disclosure;

[0008] FIG. 6 illustrates a top view of an example of the plasmonic sensor with a serpentine pattern of microfluidic channels of the present disclosure; [0009] FIG. 7 illustrates an example workflow performing a calibrated measurement using of the sensing apparatus and the plasmonic sensor of the present disclosure; and

[0010] FIG. 8 illustrates an example flowchart for a method of performing a calibrated measurement using of the sensing apparatus and the plasmonic sensor of the present disclosure.

DETAILED DESCRIPTION

[0011] Examples described herein provide plasmonic sensors with microfluidic channels. As noted above, sensors can be used to detect the presence of certain analytes and compounds in a fluid. The sensors can also be used to measure a concentration of a particular analyte. Some sensors may be plasmonic sensors that are based on surface-enhanced spectroscopies (SES) or surface plasmon resonance (SPR).

[0012] Some plasmonic sensors may not provide reliable and quantitative plasmonic sensing. Some plasmonic sensors may use manual pipetting of a solution of nanoparticles on a glass slide. These types of systems may use multiple chips, extensive manual fluid handling, preparation of dilutions and titrations, pipetting, and a controlled environment.

[0013] Examples herein provide a plasmonic sensor that uses microfluidic channels that are integrated within a plasmonic sensing substrate for efficient multi-line spectroscopy/optical calibration and detection. Several independent microfluidic channels may be formed over the plasmonic sensor with a clear capping layer. The microfluidic channels may be interleaved in space to allow for accurate in-situ calibration and quantitation of the sensing apparatus. Calibration may be achieved by flowing different fluids with one or more reference compounds with controlled concentration. The capillary structure of the plasmonic sensor provides in-situ calibration without using bulky, expensive droplet dispensers or aerosol generation, while at the same time reduces the time for optical detection using a spectrophotometer.

[0014] FIG. 1 illustrates a block diagram of an example sensing apparatus 100 of the present disclosure. In an example, the sensing apparatus 100 may include a sensor 102 of the present disclosure. The sensor 102 may be a plasmonic sensor that includes multiple integrated channels. The sensor 102 of the present disclosure may help obtain a calibrated measurement for accurate analyte quantitation. The sensing apparatus 100 helps to collect the sensor data more efficiently and quickly than using other types of optical apparatuses. Further details of the sensor 102 are illustrated in FIG. 3, and discussed in further details below.

[0015] In an example, the sensing apparatus 100 may include a light source 104 and a second sensor 106. The light source 104 may emit a laser light source that is redirected in desired patterns of light beams towards the sensor 102. The light scattered by or reflected by the channels of the sensors 102 may be redirected back towards the second sensor 106.

[0016] The second sensor 106 may be an image sensor. For example, the second sensor 106 may be a charge coupled device (CCD) sensor that can covert the light impinging on it into a image 128. The image 128 may be a digital image. The image 128 may include a response 130 of the light beam scattered by each channel of the sensor 102, as discussed in further details below. One set of channels may include a control fluid or a fluid with a known concentration of an analyte. The second set of channels may include a fluid sample with an unknown concentration which is to be measured. The responses 130 of the light scattered by the channels containing the control fluid or the fluid with the known amount of analyte may be used to calibrate the sensing apparatus 100 for subsequent detection of concentrations of the analyte in the fluid contained in the second set of channels.

[0017] In an example, the sensing apparatus may also include an optical filter 108, a pattern generator 110, a beam splitter 112, an objective lens 114 with an actuator 116, an optical filter 118, a slit array 120, a grating, prism, or other dispersive element 122, and a lens 124. In an example, the optical filter 108 may be positioned downstream from the light source 104 and used to filter out any undesired wavelengths of light.

[0018] In an example, the pattern generator 110 may be located downstream from the optical filter 108. The pattern generator 110 may split the light beam from the light source 104 into a plurality of light beams. The plurality of light beams may be arranged in a pattern that is associated with the pattern of the channels on the sensor 102. The pattern generator 110 may be implemented as a holographic spot pattern generator, a spatial light modulator, a digital micro mirror device, a metallic holographic mask, and the like [0019] FIG. 2 illustrates a few different examples of the pattern generator 110. In an example, the pattern generator 110 may be a micro-electro- mechanical system (MEMS) device 202. For example, the MEMS device 202 may include a plurality of mirrors. The angles of the mirrors may be controlled electronically and moved mechanically into positions to scatter the light beams at desired angles and patterns.

[0020] In an example, the pattern generator 110 may be a lens array 204. Each lens of the lens array 204 may have a particular shape to generate a plurality of light beams in a desired pattern. The lens array 204 may be comprised of cylindrical shaped lenses, sinusoidal cylindrical shaped optical elements, and the like.

[0021] In an example, the pattern generator 110 may include a rotating pin hole array 206. The rotating pin-hole array 206 may rotate around an axis, as shown by an arrow 208. The rotating pin-hole array 206 may include a series of holes 210i to 210_n (hereinafter also referred to individually as a hole 210 or collectively as holes 210). A first set of holes 210 may be on a first portion of the pin-hole array and a second set of holes 210 may be on a second portion of the pin-hole array. The holes 210 may be arranged to form a desired pattern of a light beam 212 that passes through the holes 210.

[0022] It should be noted that the rotating pin-hole array 206 has been simplified for ease of explanation. For example, the rotating pin-hole array 206 may include additional mirrors and lenses to redirect the light beam 212 from the light source 104 towards the holes 210.

[0023] Referring back to FIG. 1 , the beam splitter 112 may be located downstream from the pattern generator 110. The beam splitter 112 may be a dichroic beam splitter that reflects the light beams in one direction towards the sensor 102 and allows transmission of the light beams to the second sensor 106 in a second direction.

[0024] In an example, the optical filter 118 may be located downstream from the beam splitter 112. The optical filter 118 may remove any wavelengths of unwanted light. In other words, the optical filter 118 may ensure that the light beams scattered by the sensor 102 are allowed to pass through towards the second sensor 106 without any additional background light.

[0025] In an example, a slit array 120 may be located downstream of the optical filter 118. The slit array 120 may provide selective light collection from specific locations on the first sensor 102, for example from a set of evenly spaced lines (corresponding to the image of the slit array onto the first sensor 102). The size and spacing of the slits in the slit array 120 is much larger than the wavelength of light used, with slit sizes, as well as spacing, ranging between 10 microns and 300 microns.

[0026] In an example, the grating 122 may be an optical component with a desired pattern to disperse different light wavelengths at different angles. For example, the grating 122 may redirected light into a pattern that directs each scattered wavelength in the detected light beam to a particular area of the second sensor 106. As a result, each response 130 of the image 128 may be easily correlated to a particular scattered light beam from a channel on the sensor 102 as well as a particular wavelength of the scattered light.

[0027] In an example, the lens 124 may be located downstream from the grating 122. The lens 124 may help to focus the scattered light beams emitted from the grating 122 onto the desired locations of the second sensor 106.

[0028] FIG. 3 illustrates a top view of an example sensor 102 of the present disclosure. As noted above, the sensor 102 may be a plasmonic sensor. The sensor 102 may include an active area 312 formed on a substrate 310. The substrate 310 may be a silicon substrate. The active area 312 may include nanostructures made of a metal coating and an underlying mechanical nanostructure or nanostructure layer. The nanostructures may be fabricated on top of the substrate 310. The substrate 310 may be a silicon wafer, quartz, plastic, and the like.

[0029] In an example, the metal coating of the nanostructures in the active area 312 may be gold, silver, copper, and the like. In some examples, the metal coating of the nanostructures may be functionalized (e.g., with various compounds such as carboxylic acid) to connect to target molecules that may be present in the fluids that pass across the active area 312. The substrate 310 and the active area 312 may form a nanostructured substrate. The active area 312 may be a surface enhanced Raman spectroscopy (SERS) surface.

[0030] In an example, a layer of photo-definable polymer may be deposited onto the substrate 310 and the active area 312. The photo-definable polymer may be SU8. In an example, the photo-definable polymer may be coupled to the substrate 310 and the active area 312 using an adhesion layer. For example, if the active area 312 is coated with gold, the adhesion layer may also be gold to provide a gold-gold bonding.

[0031] In an example, the photo-definable polymer may be processed using photolithography methods to form a first set of microfluidic channels 306i - 306_m (hereinafter also referred to individually as a channel 306 or collectively as channels 306) with an inlet 302 and outlets 308i to 308_m (hereinafter also referred to individually as an outlet 308 or collectively as outlets 308). The photo-definable polymer may be processed to also form a second set of microfluidic channels 310i - 310_o (hereinafter also referred to individually as a channel 310 or collectively as channels 310) with an inlet 304 and outlets 312i to 312_o (hereinafter also referred to individually as an outlet 312 or collectively as outlets 312).

[0032] As can be seen in FIG. 3, the channels 306 and 310 may be interleaved. In other words, the first set of microfluidic channels 306 may be formed to alternate in-between the second set of microfluidic channels 310.

Said another way, the channels 306 and 310 may be formed in an alternating pattern. [0033] In an example, the channels 306 and the channels 310 may be formed in opposite directions. For example, the first inlet 302 and the second inlet 304 may be located on opposite sides of substrate 310. Thus, a first fluid that is provided through the first inlet 302 may flow through the first set of microfluidic channels 306 in a first direction. A second fluid that is different than the first fluid may be provided through the second inlet 304 and flow through the second set of microfluidic channels 310 in a second direction. The second direction may be in a direction that is opposite the first direction. For example, if the first fluid flows from left to right on the page, the second fluid may flow from right to left on the page. As discussed in further details below, in some examples, the first fluid and the second fluid may flow in a same direction.

[0034] In an example, the first inlet 302 and the second inlet 304 may be reservoirs. For example, a reservoir may be punctured to begin the flow of the first fluid or the second fluid through the channels 306 and 310, respectively.

The first fluid and the second fluid may flow through the channels 306 and 310, respectively, via capillary forces.

[0035] In another example, the first inlet 302 and the second inlet 304 may be connected to a pump and a storage container or area. The pump may be activated to move the first fluid and the second fluid from the respective storage containers through the channels 306 and 310, respectively.

[0036] In an example, the channels 306 and 310 may have a width of approximately 50 microns. The channels 306 and 310 may be spaced apart by a distance of approximately 30 microns. The inlets 302 and 304 may have a diameter of approximately 300 microns. The outlets 308 and 312 may have a diameter of approximately 80 microns. However, it should be noted that the dimensions of the various components of the sensor 102 may vary based on a particular application, the types of fluids that are analyzed, and the like.

[0037] FIG. 4 illustrates a cross-sectional view of the sensor 102. In an example, a clear capping layer 314 may be placed over the channels 306 and 310. The clear capping layer 314 may be an optically clear glass or plastic that allows light to pass through and into the channels 306 and 310.

[0038] As can be seen in FIG. 4, the channels 306 and 310 may be formed to lie on a common plane. In other words, the channels 306 and 310 may be formed such that the respective distances from the center of the channels 306 and 310 to a top surface of the clear capping layer 314 are equal.

[0039] In an example, the active area 312 may be formed to have a large continuous surface. As a result, the active area 312 may be large enough to accommodate the channels 306 and 310 that are formed over the active area 312. FIG. 5 illustrates different examples of how the active area 312 may be formed.

[0040] In an example 502, the active area 312 may be patterned to be within each channel 306 and 312. In other words, instead of a single large continuous area, the active area 312 may be patterned to correspond to the channels 306 and 312 that are formed over the patterned active area 312.

[0041] In an example 504, the channels 306 and 310 may be pre-loaded with a dried physiosorbed, or lyophilized compound. The compound may be a reference compound or other additives to better enable calibration and quantitation. Thus, as the first fluid and the second fluid are inserted into the channels 306 and 310, respectively, the compounds may be absorbed into the first fluid and second fluid and used for calibration.

[0042] In an example, 506, the active area 312 may be replaced with colloidal nanoparticles 318. The nanoparticles 318 may be introduced into the channels 306 and 310 and provide the active area 312 for detection and calibration of analytes in the first fluid and the second fluid that flow through the channels 306 and 310, respectively. The substrate 310 might in this example be coated with a uniform and planar metal film. The nanoparticles may also be pre-loaded in the channels before use.

[0043] FIG. 6 illustrates a top view of another example of a plasmonic sensor 602. In an example, the plasmonic sensor 602 may have an active area 614 formed on a substrate 612. A first set of microfluidic channels 616 and a second set of microfluidic channels 618 may be formed in a photo-definable polymer layer deposited over the active area 614. A clear capping layer (not shown in the top view) may also be formed over the channels 616 and 618.

[0044] In an example, a first inlet 604 and a first outlet 608 may be associated with the first set of microfluidic channels 616. A second inlet 606 and a second outlet 610 may be associated with the second set of microfluidic channels 618. A first fluid may be provided through the first inlet 604 and through the first set of microfluidic channels 616. A second fluid may be provided through the second inlet 606 and through the second set of microfluidic channels 618.

[0045] The first fluid may be different than the second fluid. The first fluid and the second fluid may flow in the same direction in the example shown in FIG. 6 (e.g., from the top towards the bottom of the page).

[0046] In an example, the channels 616 and 618 may be arranged in a serpentine pattern on a common plane. For example, the channels 616 and 618 may be interleaved, but arranged to be curved and travel back and forth across the active area 614. Box 624 illustrates a close-up view of how the channels 616 and 618 curve around one another in the serpentine pattern. [0047] In the example illustrated in FIG. 6, the channels 616 and 618 may have a width 620 of approximately 30 microns. In an example, a spacing 622 between the channels 616 and 618 may be approximately 15 microns. Although the examples illustrated herein use two different sets of microfluidic channels, it should be noted that more than two different sets of microfluidic channels may be deployed.

[0048] FIG. 7 illustrates a process workflow 700 of performing a calibrated measurement using the sensing apparatus 100 and the plasmonic sensor 102 of the present disclosure. FIG. 8 illustrates a flowchart for a method 800 of performing a calibrated measurement with the sensing apparatus and the plasmonic sensor of the present disclosure. In an example, the method 800 may be performed by the sensing apparatus 100 illustrated in FIG. 1 , and described above. The blocks of FIG. 8 may be described with reference to the process workflow illustrated in FIG. 7.

[0049] At block 802, the method 800 begins. At block 804, the method 800 fills a first set of microfluidic channels that are located over a sensor with a control fluid. The control fluid may be a fluid containing a known amount of analyte. The control fluid may be a fluid that has a known sensor response. The control fluid may be delivered via the inlet 302 through the first set of microfluidic channels 306 illustrated in FIG. 7.

[0050] At block 806, the method 800 fills a second set of microfluidic channels that are located over the sensor with a fluid containing an unknown amount of analyte to be determined. As shown in block 702 of FIG. 7 the fluid may be delivered via the inlet 304 through the second set of microfluidic channels 310. The sensor response may then be correlated to the known amount of the analyte in the first fluid, and thus, determine the unknown concentration in the second fluid. The correlation may be used to calibrate the sensing apparatus, as discussed below.

[0051] The control fluid and the fluid with the unknown amount of analyte may be allowed to incubate in the channels 306 and 310 after delivery, as shown in block 704 of FIG. 7. The amount of time may be predetermined. The amount of time may be a sufficient amount of time to allow the analyte to interact with the plasmonic sensor 102 to provide a sufficiently intense surface enhanced spectroscopic signal.

[0052] At block 808, the method 800 removes the control fluid and the fluid containing the unknown amount of analyte. For example, the control fluid and the fluid containing the unknown amount of analyte may be removed via respective outlets. As shown in block 706, the channels 306 and 310 may be emptied. In an example, the channels 306 and 310 may be dried (e.g., by flowing compressed air through the inlets 302 and 304).

[0053] At block 810, the method 800 applies a light beam to the first set of microfluidic channels. For example, a spectrometer 720 may emit light through an objective lens 722 onto the plasmonic sensor 102, as shown in block 708 of FIG. 7. The spectrometer 720 may emit light in a desired pattern that is focused by the objective lens 722 onto the first set of microfluidic channels 306.

[0054] At block 812, the method 800 measures a response to the light beam aligned to the first set of microfluidic channels. For example, the light scattered by the plasmonic active area within microfluidic channels 306 may be received by the spectrometer 720. The spectrometer 720 may then measure the response to the light beam. The response may be converted into an image. The image may contain a response for each channel 306 of the first set of microfluidic channels, as well as wavelength specific information.

[0055] At block 814, the method 800 applies the light beam to the second set of microfluidic channels. For example, the spectrometer 720 may change the pattern of light emitted to correspond to the locations of the second set of microfluidic channels 310, as shown in block 710 of FIG. 7. For example, a pattern generator may be shifted, moved, or rotated to redirect the light emitted from the spectrometer 720 to the first set of microfluidic channels 306 to the second set of microfluidic channels 310. Otherwise the spectrometer 720 can be translated, moved, or rotated with respect to the plasmonic sensor 102 or vice versa the sensor 102 can be moved, translated, or rotated with respect to the spectrometer 720.

[0056] At block 816, the method 800 measures a response to the light beam aligned to the second set of microfluidic channels. For example, the light scattered by the plasmonic active area within the microfluidic channels 310 may be received by the spectrometer 720. The spectrometer 720 may then measure the response to the light beam. The response may be converted into an image. The image may contain a response for each channel 310 of the second set of microfluidic channels.

[0057] In an example, a relative shift 724 may be used to reach the configuration that will allow for determination of the response for the analyte that is being detected. For example, the response of the fluid with the unknown analyte may be divided by the response of the analyte in the control fluid to obtain a calibrated measurement of the unknown amount of analyte in the test fluid.

[0058] At block 818, the method 800 performs a calibrated measurement using a sensing apparatus and a plasmonic sensor based on the response to the light beam on the first set of microfluidic channels and the response to the light beam on the second set of microfluidic channels. In an example, the method 800 may be repeated several times for different amounts of the known analyte. In another example, the method 800 may include more than two fluids, and more than one control fluid. A curve or line may be fit to the data to correlate the response to the amount of analyte that is detected. The sensing apparatus may then accurately detect and calculate an amount of analyte in a fluid for subsequently fed fluids.

[0059] In an example, more than two channels containing a variety of lyophilized additives or filled with several control fluids with different concentrations and mixtures can be used to make more robust spectroscopic comparisons between control fluids and calibration fluids. Furthermore, the control fluid could be the same test fluid, which is filled into channels containing additives in predetermined concentrations. At block 820, the method 800 ends. [0060] It will be appreciated that variants of the above-disclosed and other features and functions, or alternatives thereof, may be combined into many other different systems or applications. Various presently unforeseen or unanticipated alternatives, modifications, variations, or improvements therein may be subsequently made by those skilled in the art which are also intended to be encompassed by the following claims.

Claims

1. A sensor, comprising: a plasmonic sensor formed on a substrate; a first set of microfluidic channels located over the plasmonic sensor; a first inlet to provide a first fluid to flow through the first set of microfluidic channels and over the plasmonic sensor; a second set of microfluidic channels located over the plasmonic sensor and interleaved with the first set of microfluidic channels; a second inlet to provide a second fluid to flow through the second set of microfluidic channels and over the plasmonic sensor; and a clear capping layer formed over the first set of microfluidic channels and the second set of microfluidic channels.

2. The sensor of claim 1 , wherein the first set of microfluidic channels and the second set of microfluidic channels lie on a common plane.

3. The sensor of claim 1 , wherein the first set of microfluidic channels and the second set of microfluidic channels are arranged in a serpentine pattern.

4. The sensor of claim 1 , wherein the first inlet and the second inlet are coupled to a pump.

5. The sensor of claim 1 , wherein the first set of microfluidic channels and the second set of microfluidic channels are formed in a photo-definable polymer layer.

6. The sensor of claim 1 , wherein the second fluid flows in an opposite direction of the first fluid.

7. A sensing apparatus, comprising: a light source to emit a light; a pattern generator to split the light into a plurality of light beams; a sensor comprising a first set of microfluidic channels containing a first fluid and a second set of microfluidic channels containing a second fluid, wherein the plurality of light beams is directed at the first set of microfluidic channels or the second set of microfluidic channels; and an optical sensor to capture scattered light beams from the sensor.

8. The sensing apparatus of claim 7, further comprising: an actuator to align the plurality of light beams with the first set of microfluidic channels or the second set of microfluidic channels.

9. The sensing apparatus of claim 7, wherein the pattern generator comprises at least one of: a microelectromechanical system (MEMS) of mirrors, a cylindrical lens array, or a rotating pin-hole array.

10. The sensing apparatus of claim 7, wherein the optical sensor comprises a charge-coupled device (CCD) to generate an image of the scattered light beams from the sensor.

11. The sensing apparatus of claim 7, wherein the sensor comprises a dried physiosorbed compound in the first set of microfluidic channels and the second set of microfluidic channels.

12. The sensing apparatus of claim 7, wherein the sensor comprises a fluid with nanocolloids is introduced into the first set of microfluidic channels and the second set of microfluidic channels.

13. A method, comprising: filling a first set of microfluidic channels that is located over a sensor with a control fluid; filling a second set of microfluidic channels that is located over the sensor with a fluid containing an unknown amount of analyte to be determined ; removing the control fluid and the fluid containing the unknown amount of analyte; applying a light beam to the first set of microfluidic channels; measuring a response to the light beam aligned to the first set of microfluidic channels; applying the light beam to the second set of microfluidic channels; measuring a response to the light beam aligned to the second set of microfluidic channels; and performing a calibrated measurement using a sensing apparatus and a plasmonic sensor based on the response to the light beam on the first set of microfluidic channels and the response to the light beam on the second set of microfluidic channels.

14. The method of claim 13, further comprising: incubating the control fluid in the first set of microfluidic channels and incubating the fluid containing the unknown amount of analyte in the second set of microfluidic channels for a predefined amount of time.

15. The method of claim 13, further comprising: drying the first set of microfluidic channels and the second set of microfluidic channels after the control fluid and the fluid containing the unknown amount of analyte are removed.