Swept-angle SPR measurement system

Surface plasmon resonance (SPR) measurement systems rely on surface plasmon resonances to detect changes in refractive index of a target at a transducing interface. Due to the surface plasmon resonance phenomenon, optical signals that are incident on the transducing interface undergo a loss at a resonant incidence angle. Changes in the refractive index of the target cause changes in the resonant incidence angle that can be detected by measurements of the intensity of optical signals that are deflected by the target. An SPR measurement system relates detected changes in the resonant incidence angle to corresponding changes in the refractive index of the target, typically in the form of an SPR sensorgram, which is a plot of the relative refractive index of the sample versus time. SPR sensorgrams can be used to characterize biochemical processes at the transducing interface based on relationships between the biochemical processes and refractive indices of the targets at the transducing interface.

A prior art SPR measurement system (shown in FIG. 1 ) detects shifts in resonant incidence angle by measuring the intensity of the optical signals deflected by the target while mechanical actuators rotate the target over an angular adjustment range +/−2.5 degrees to vary the incidence angle of the target relative to an incident optical beam. Because some biochemical processes can produce shifts in resonant incidence angle of less than 10 −4 degrees, it may be desirable for the SPR measurement system to have capability to measure small shifts in resonant incidence angle that are induced by changes in refractive index. In addition, it may be desirable for angular rotation of the target to occur at high repetition rates to detect biochemical processes of short duration at the transducing interface. However, the precision of the measurements of the resonant incidence angle, and the repetition rates for detecting biochemical processes at the transducing interface are limited by the mechanical actuators used in the SPR measurement system to provide the angular rotations of the target.

A swept-angle SPR measurement system according to embodiments of the present invention deflects an optical beam over a range of deflection angles according to a control signal and maps the deflected beam to a target within a range of incidence angles that corresponds to the range of deflection angles.

FIG. 1 shows a prior art SPR measurement system.

FIG. 2 shows a swept-angle SPR measurement system according to embodiments of the present invention.

FIG. 3 shows one example of a response characteristic of an acousto-beam deflector suitable for inclusion in the swept-angle SPR measurement system of FIG. 1 .

FIGS. 4A-4B show optical beams incident on an optical aperture of an acousto-beam deflector.

FIG. 5A one example of a shift in resonant incidence angle detected by the swept-angle SPR measurement system according to embodiments of the present invention.

FIG. 5B shows one example of an SPR sensorgram provided by the swept-angle SPR measurement system according to embodiments of the present invention.

FIG. 6 shows a flow diagram of a swept-angle SPR measurement system implemented as a method, according to alternative embodiments of the present invention.

FIG. 2 shows a swept-angle SPR measurement system 10 according to embodiments of the present invention. The swept-angle SPR measurement system 10 , hereinafter “measurement system 10 ”, includes an optical source 12 , a beam deflector 14 , and an imaging telescope 16 that directs optical beams provided by the beam deflector 14 to a target T.

The optical source 12 provides a collimated optical signal, designated as optical beam B 1 . Typically, the optical source 12 includes an LED, a laser, or a superluminescent light source. The optical source 12 can provide an optical signal 11 having a single wavelength, multiple wavelengths, or wavelengths that are selectable. However, the optical source 12 can include any other type of emitter 8 suitable for providing an optical signal 11 having sufficiently stable wavelength and intensity characteristics over a measurement acquisition interval of the measurement system 10 , so as not to corrupt measurements that are acquired by the measurement system 10 . When the optical signal 11 provided by the emitter 8 is not collimated, the optical source 12 includes a collimator C cascaded with the emitter 8 to collimate the optical beam B 1 . The beam deflector 14 may have a narrow range of incident angles within which incident optical beams, such as the optical beam B 1 , are efficiently deflected. Collimating the optical beam B 1 prevents the optical beam B 1 from diverging from an optimum input angle α OPT , improving the efficiency of the beam deflector 14 and raising the optical power of deflected beams B 2 that are provided by the beam deflector 14 . FIG. 3 shows one example of an efficiency contour 13 associated with the beam deflector 14 , indicating that even slight deviations from the optimum input angle a OPT can substantially decrease relative optical power in the deflected beams B 2 that are provided by the beam deflector 14 due to decreases in power deflection efficiency that accompany deviations from the optimum input angle α OPT . For a typical beam deflector 14 , collimation of the optical beam B 1 in the plane that contains the deflection angle φ of the deflected beam B 2 is sufficient to provide efficient deflection of the optical beam B 1 by the beam deflector 14 . However, the collimator C typically includes elements to also collimate the optical beam B 1 in a direction orthogonal to the plane that contains the deflection angle φ of the deflected beam B 2 .

The collimator C can also transform the shape of the optical signal 11 provided by the emitter 8 so that the optical beam B 1 provided by the optical source 12 accommodates the dimensional aspects of an optical aperture associated with the beam deflector 14 . Typically, the collimator C shapes and sizes the optical beam B 1 to be consistent with the optical aperture of the beam deflector 14 . This enables efficient transfer of optical power from the optical beam B 1 to the deflected beam B 2 . In one example the emitter 8 provides an optical signal 11 that has a circular shape, and the optical aperture of the beam deflector 14 is rectangular. In this example, the collimator C includes one or more cylindrical lenses to transform the circular shape of the optical signal 11 to an elliptical shape in the optical beam B 1 . The elliptical shape accommodates the rectangular optical aperture A RECT of the beam deflector 14 as shown in FIG. 4A . In another example, the optical aperture of the beam deflector 14 is rectangular and the emitter 8 provides an optical signal 11 that has an elliptical shape. In this example, the collimator C can include one or more spherical lenses to collimate the optical signal 11 into an optical beam B 1 that accommodates the rectangular optical aperture A RECT of the optical detector 14 as shown in FIG. 4A . In another example, the emitter 8 provides an optical signal 11 that has a circular shape and the optical aperture of the beam deflector 14 is square. In this example, the collimator C can include one or more spherical lenses to collimate the optical signal 11 into the optical beam B 1 that accommodates the square optical aperture A SQ of the beam deflector 14 shown in FIG. 4B . In another example, the optical aperture of the beam deflector 14 is square, and the emitter 8 provides an optical signal 11 that has an elliptical shape. In this example, the collimator C can include cylindrical lenses to accommodate the square optical aperture A SQ of the beam deflector 14 . While examples of collimators C that include spherical and/or cylindrical lenses have been provided for the purpose of illustration, the collimator C can alternatively include any suitable device, element or system that provides a sufficient collimation of the optical beam B 1 for deflection of the optical beam B 1 by the beam deflector 14 . The collimator C can also include any suitable device, element or system for shaping of the optical beam B 1 to accommodate the optical aperture of the beam deflector 14 .

The beam deflector 14 deflects, or changes the direction of, an applied signal, such as the optical beam B 1 , to provide a corresponding deflected beam B 2 . According to one embodiment of the present invention, shown in FIG. 2 , the beam deflector 14 includes an acousto-optic deflector. Acousto-optic deflectors are known in the art and are available from a variety of sources, including Crystal Technologies, Inc., for example. The acousto-optic deflector deflects the optical beam B 1 according to a control signal 15 by a deflection angle φ based on the relationship Δφ=λ(Δf/Va), where λ is the optical wavelength of the optical beam B 1 , Δf is the frequency bandwidth of the acousto-optic deflector, and Va is the acoustic velocity of the acousto-optic deflector. This relationship indicates that the acousto-optic deflector deflects the optical beam B 1 in proportion to the frequency f of the control signal applied to the acousto-optic deflector. In the example shown in FIG. 2 , a function generator, voltage controlled oscillator (VCO), or other signal source drives the acousto-optic deflector by providing a control signal that is swept, tuned, or otherwise adjusted in frequency f over a frequency range between a frequency f 1 and a frequency f 2 . In one example, an optical beam B 1 incident on the acousto-optic deflector at an incidence angle of 0.45 degrees provides deflected beams B 2 over a range of deflection angles Δφ of 2.9 degrees in response to an applied control signal 15 within the frequency range of 35 MHz-70 MHz.

According to alternative embodiments of the present invention, the beam deflector 14 includes a MEMS device (not shown) that has one or more optical reflectors or other devices that provide deflected beams B 2 over a range of deflection angles. Typically, the MEMS device includes a focusing element to focus the optical beam B 1 provided by the optical source onto one or more reflectors in the MEMS device. A collimating element can then be cascaded with the one or more reflectors in the MEMS device to provide deflected beams B 2 that are collimated. The deflection angles of the deflected beams B 2 provided by the MEMS device are established according to a control signal, applied to the MEMS device, which causes rotation of the one or more reflectors of the MEMS device.

The imaging telescope 16 receives the deflected beams B 2 over a range Δφ of deflection angles φ that are provided by the beam deflector 14 and directs the deflected beams B 2 to the target T. Typically, the target T is proximate to a transducing interface 17 of an SPR transducer 18 , at a transducing interface 17 of an SPR transducer 18 , or the target T is otherwise associated with a transducing interface 17 of an SPR transducer 18 .

The target T typically contains one or more designated regions or samples for illumination. SPR transducers are known in the art and are shown in references such as Characterization and Optimization of a Real - Time, Parallel, Label - Free, Polypyrrole - Based DNA Sensor by Surface Plasmon Resonance Imaging , by Guedon et al., Analytical Chemistry, Vol. 72, No. 24, Dec. 15, 2000, pages 6003-6009.

The deflected beams B 2 that are directed by the imaging telescope 16 result in incident beams B 3 that illuminate the target T. The action of the beam deflector 14 and the imaging telescope 16 enable the target T, to be illuminated at a fixed position or location, that is independent of the angle of incidence of the incident beam B 3 . Thus, the angle of incidence of the incident beam B 3 can be swept, tuned, varied, or otherwise adjusted via the action of the beam deflector 14 , and directed to a target T via the action of the imaging telescope 16 , so that the illumination provided by the resulting incident beam B 3 is fixed in location or position due to the adjustment of the angle of incidence of the incident beam B 3 . The imaging telescope 16 maps the deflection angles φ of the deflected beam B 2 that are within a designated range Δφ, to corresponding incident angles Φ INC that are within a corresponding range ΔΦ to provide the incident beam B 3 .

The incident beam B 3 illuminates the target T at a fixed position when the incident angles Φ INC of the incident optical beam B 3 are within the range ΔΦ.

Typically, the imaging telescope 16 includes a cascaded series of two or more lenses. The imaging telescope 16 magnifies the size of the deflected beam B 2 , based on selection of the focal lengths of the two or more lenses included in the imaging telescope 16 to adjust the size the illumination spot provided by the incident beam B 3 at the target T. The magnification provided by the imaging telescope 16 can reduce or increase the size of the incident optical beam B 3 relative to the size of the deflected beam B 2 . For example, if a first lens L 1 has a focal length F 1 , and a second lens L 2 has a focal length F 2 , a magnification to the size of the deflected beam B 2 by a factor F 2 /F 1 can be achieved for the incident beam B 3 by the imaging telescope 16 . When the focal length F 2 is greater than the focal length F 1 , the incident beam B 3 is larger than the deflected beam B 2 . When the focal length F 1 is greater than the focal length F 2 , the incident beam B 2 is larger than the deflected beam B 3 . FIG. 2 shows an example wherein the imaging telescope 16 includes two spherical lenses that provide uniform magnification across the deflected beam B 2 . Cylindrical lenses can also be included in the imaging telescope 16 to provide magnification to vary the size of the deflected beam B 2 along an axis of the incident beam B 3 that is established by the orientation of the cylindrical lenses. For example, a first pair of cylindrical lenses can provide a first magnification along a first axis perpendicular to the direction of propagation of the deflected beam B 2 , while a second pair of cylindrical lenses orthogonal to the first pair of cylindrical lenses can provide a second magnification along a second axis perpendicular to the first axis and perpendicular to the direction of propagation of the deflected beam B 2 .

The imaging telescope 16 also enables the incidence angle of the incident beam B 3 at the target T to be a multiple of the deflection angle φ of the optical beam B 2 . A multiplication factor relates the deflection angle φ of the deflected beam B 2 to the incidence angle Φ INC of the incident optical beam B 3 . The range ΔΦ INC of incident angles Φ INC can be greater than, less than, or equal to the range Δφ of deflection angles φ. For example, when the beam deflector 14 provides deflected beams B 2 over a range of angles of 2.9 degrees, a magnification factor of two provided by the imaging telescope 16 correspondingly multiplies the range of incidence angles Φ INC to 5.8 degrees, provided that the magnification is in the plane that includes the deflection angle φ.

The multiplication provided by the imaging telescope 16 can be selected based on a designated range of incidence angles at the target T, the size and shape of the target T, a nominal angle of incidence at the target T, and a range Δφ of deflection angles φ. In one example, for a range ΔΦ INC of incident angles Φ INC of 5.8 degrees, a nominal incidence angle of 65 degrees, a spot size of 14 mm, and a range range Δφ of deflection angles φ of 2.9 degrees, a multiplication of two is suitable and can be achieved via the factor F 2 /F 1 . However, the magnification or multiplication provided by the imaging telescope 16 can also be selected according to the size, type and orientation of the optical devices, elements, or systems included in the imaging telescope 16 . The imaging telescope 16 also maintains collimation of the deflected beam B 2 at the incident beam B 3 .

In a typical application of the measurement system 10 , a detector 20 intercepts a reflected optical signal B 4 from the target T. The detector 20 is in signal communication with the target T, detecting an intensity of the reflected optical signal B 4 as the incident angle Φ INC of the incident optical beam B 3 is swept, tuned or otherwise adjusted over the range ΔΦ INC of incident angles Φ INC that is provided by the sweeping, tuning or adjusting of the deflection angle of the deflected beam B 2 and the multiplication or magnitude provided by the imaging telescope 16 . The detector 20 is typically a device, element or system, or an array of devices, elements or systems, that convert detected optical intensities to corresponding electrical signals. In one example, the detector 20 includes one or more Si, In GaAs, or Ge detection elements.

A processor 22 coupled to the detector 20 synchronizes the adjustment of the incidence angles Φ INC via the control signal 15 that is applied to the beam deflector 14 . The processor 22 can also process the detected intensity of the reflected beam B 4 to provide an SPR sensorgram 23 or other output that indicates a shift in resonant incidence angle Φ RES associated with the target T. FIG. 5A shows one example of the detected intensity of the reflected beam B 4 indicating ΔΦ a shift in resonant incidence angle Φ RES induced by a change in refractive index of the target T. FIG. 5B shows one example of an SPR sensorgram 23 provided by the measurement system 10 , indicating refractive index shown in micro-refractive index units (10 6 RIU).

Since the target T can contain one or more designated regions or samples for illumination, a lens or other imaging element 24 can be interposed between the target T and the detector 20 to image the one or more designated regions or samples of the target T to corresponding positions on the detector 20 . This enables the measurement system 10 to measure shifts in resonant incident angle, or corresponding shifts in refractive indices of multiple samples or regions at a transducing interface 17 of an SPR transducer 18 , either in parallel or sequentially.

While a single measurement system 10 is shown in FIG. 2 , alternative embodiments of the present invention can include two or more measurement systems 10 that illuminate a single target T. In these embodiments, each of the measurement systems 10 can operate at a different optical wavelength. In one example, two measurement systems 10 illuminate a target T wherein one of the measurement systems operates at an optical wavelength of 700 nm and the other of the measurement systems operates at an optical wavelength of 1600 nm.

A polarizer P is shown included in the propagation path of the reflected beam B 4 to designate the polarization state of the reflected beam B 4 . Alternatively, polarizers can be included in the propagation paths of any of the other beams B 1 -B 4 . The measurement system 10 can also include beam splitters and optical detection elements at various locations in the optical propagation paths to monitor one or more of the beams B 1 -B 4 for calibration of the measurement system 10 . In the example shown in FIG. 2 , an optionally-included half-wave plate λ/ 2 is shown interposed between the beam deflector 14 and the imaging telescope 16 to align the polarization of the incident beam B 3 at the target T. When the target T is associated with the transducing interface 17 of an SPR transducer 18 , the half-wave plate λ/ 2 provides a p-polarization of the incident beam B 3 at the target T.

According to alternative embodiments of the present invention, the swept-angle SPR measurement system 10 is implemented according to a method 30 shown that is shown in the flow diagram of FIG. 6 . The method 30 includes varying the deflection angle φ of the deflected beam B 2 within a range of deflection angles Δφ (step 32 ). The deflected beam B 2 results from applying the optical beam B 1 provided by the optical source 12 to the beam deflector 14 and sweeping, tuning or otherwise adjusting the deflection angle (n of the deflected beam B 2 via the control signal 15 applied to the beam deflector 14 .

The method 30 then includes mapping the deflection angles φ of the deflected beam B 2 that are within the range Δφ of deflection angles φ to corresponding incidence angles Φ INC within a corresponding range ΔΦ INC of incidence angles Φ INC to provide the incident beam B 3 that illuminates the target T (step 34 ). The target T has a fixed position when the incident angle is within the range of incidence angles.

The method 30 then includes measuring the reflected beam B 4 from the target T as the incidence angle Φ INC of the optical beam B 3 at the target T is varied within the range ΔΦ INC of incidence angles Φ INC (step 36 ). Measuring the reflected beam B 4 from the target T typically includes detecting the intensity of the reflected beam B 4 and processing the detected intensity to provide an SPR sensorgram 23 .

Optional step 35 includes imaging one or more locations of the target T to one or more corresponding positions at a detector 20 .

While the embodiments of the present invention have been illustrated in detail, it should be apparent that modifications and adaptations to these embodiments may occur to one skilled in the art without departing from the scope of the present invention as set forth in the following claims.