The present invention relates to sensor equipment for use in detecting and monitoring molecular interactions. More specifically, the present invention relates to a sensor element which uses a silicon-on-insulator wafer along with a silicon prism.
The field of biological and biochemical research has significantly grown in the past decade. More and more new compounds, medicines, and techniques are being developed in these fields. One key activity for such research is the detection and monitoring of molecular interactions. Molecular binding between compounds are presently detected and monitored using a number of techniques, the most common being SPR (surface plasmon resonance).
SPR is well-known and is, at present, the only label-free sensor technology commercially available for monitoring molecular binding interactions in real time. An SPR system measures the shift in surface plasmon phase velocity or wavevector as the molecules bind to a metal film. This film is usually gold (Au) but other metals such as silver (Ag) may also be used. This measurement is accomplished by measuring the incident angle at which an incident beam couples power into the SPR mode in the metal film. An alternative to measuring this incident angle is to fix the incident angle and then measure that wavelength at which SPR-incident beam coupling is achieved.
In both of the two methods, the incident beam is coupled to the backside of the metal film through a glass prism. The glass prism is necessary to satisfy the required wave vector matching between the incident beam and the plasmon mode. Coupling of power to the SPR mode is observed as a dip in the power of the beam reflected from the metal film.
While useful, SPR has its drawbacks. Specifically, the SPR response is very broad due to the extremely short propagation length of a plasmon. In a gold film at a wavelength of λ=800 nm, this length is only 20 μm. As a result, when molecules bind to the SPR surface, the shift in SPR resonance is a small fraction of the SPR resonance linewidth, and the corresponding change in reflectivity is only a few percent. This, unfortunately, limits the ultimate sensitivity of the SPR technique.
At longer wavelengths (e.g. near λ=1550 nm), the response of SPR to molecular binding is even lower as the plasmon field expands into the upper cladding of the sensor. This reduces the coupling to a molecular film on the metal surface. Working at longer wavelengths is, therefore, inadvisable for the SPR technique.
There is therefore a need for methods and devices that mitigate if not overcome the shortcomings of the prior art. Specifically, there is a need for techniques and devices which can work at longer wavelengths and whose sensitivity is not limited by the short propagation length of a plasmon.
The present invention provides methods and devices related to a sensor element for use in the detection and monitoring of molecular interactions. The sensor element uses a silicon-on-insulator wafer optically coupled to a silicon prism. The wafer has a thin silicon film top layer, a silicon substrate layer, and a buried silicon dioxide layer sandwiched between the silicon film and substrate layers. The wafer is coupled to the prism on the wafer's substrate side while the interactions to be monitored are placed on the wafer's silicon film side. An incident beam is directed at the prism and the incident angle is adjusted until the beam optically couples to the silicon film's optical waveguide mode. When this occurs, a decrease in the intensity of the reflected beam can be detected. The molecular interactions affect the phase velocity or wave vector of the propagating mode. Similarly, instead of measuring the incident angle at which optical coupling occurs, the phase of the reflected beam may be measured.
In one aspect, the invention provides a sensor for use in molecular monitoring and detection, the sensor comprising:
In another aspect, the present invention provides a method for determining a resonance characteristic for use in detecting or monitoring molecular interactions using a prism coupled sensor having a silicon on insulator sensor element, the method comprising:
A better understanding of the invention will be obtained by considering the detailed description below, with reference to the following drawings in which:
Referring to
As can be seen from
It should be noted that the ambient bulk medium above the sensor is water for the data in
It should be noted that the data for
If a silicon (Si) prism is used with the gold film using the same setup as in
According to one embodiment of the invention, the gold film may be replaced with a silicon-on-insulator wafer, and the glass prism with a silicon prism. Referring to
In use, an incident beam 130 passes through the prism 80 at an incident angle θ and is reflected off the silicon layer 110 as reflected light 140. The silicon layer 90C supports an optical waveguide mode that is localized to the near surface region at a wavelength of =1550 nm. This strongly couples to molecules bound to the surface of the silicon layer. As molecules bind to this surface, the phase velocity or wave vector of the propagating mode is perturbed with a corresponding change in the refractive index of the material. This change in phase velocity or wave vector is detectable through a change in the reflectivity of the incident beam 130 in a manner similar to the SPR technique.
Thus, at a critical θ, the incident beam 130 couples to the waveguide mode of the silicon layer 90C and this produces a corresponding decrease in the intensity of the reflected light 140 (or a corresponding decrease in the reflectivity of the incident beam 130). This decrease can be seen as a significant dip in the reflectivity vs. incident angle graph in
The silicon on insulator wafer 90 may be an electronics grade wafer with the substrate layer being transparent to the incident wavelength The substrate layer should allow optical coupling between the prism and the substrate. The silicon dioxide layer should be thin enough to provide optical coupling between the silicon substrate and the silicon film layer (<1 micron). The silicon film layer may be approximately 0.2 microns, significantly thinner than the substrate layer. Experiments have shown optimal results with a silicon layer of 0.22 microns.
Similar to SPR, there should be good optical coupling between the prism 80 and the sensor element 90. Preferably, the wavelength of the incident beam used with the sensor element 90 be in the range where silicon is transparent. This range approximately begins at =1200 nm or longer but experiments have found that =1550 nm is a convenient value as very accurate tunable lasers operating in approximately this wavelength range are available. These lasers, usually used for telecommunications testing, may be used for interrogation, thereby improving the sensitivity of the sensor.
Regarding the prism 80, the silicon prism is provided to ensure that proper wave vector matching conditions can be achieved in a manner similar to an SPR sensor.
It should be noted that while the sensor 70 may be used by measuring the variation of the reflected beam power as either the incident angle or the wavelength is scanned, it may also be used by measuring the variation of the phase of the reflected beam with wavelength or incident angle. Thus, instead of detecting the decrease in the reflectivity of the incident beam or the decrease in intensity of the reflected beam, a phase discontinuity in the reflected beam may be detected. Near resonance (when the incident light couples to the silicon layer's waveguide mode), the reflected beam also undergoes significant phase changes as the incident angle or wavelength pass through the resonance condition. This discontinuity in the phase of the reflected beam may be detected and measured as opposed to the intensity of the reflected light or the reflectivity of the incident beam.
As can be imagined, the process for detecting and monitoring the phase discontinuities of the reflected light is akin to the process for scanning the incident angle and/or the incident light wavelength that causes the coupling between the incident light and the waveguide mode of the silicon layer. First, the incident light is directed at the prism. The phase of the reflected light is then detected. Then, depending on whether incident angle scanning or wavelength scanning is employed, the angle of the incident light or the wavelength of the incident light is adjusted. The angle or wavelength for which the discontinuity of the phase of the reflected light occurs is noted. The angle or wavelength at which the incident light couples to the waveguide mode is usually noted as the angle or wavelength at which the phase crosses the baseline phase value (the regular phase value of the reflected light or a background reference phase value) in a plot of the phase vs either angle or the wavelength. This can be seen as the phase value shifts from a value lower than the baseline to a value higher than the baseline or as the phase value shifts from a higher than baseline value to a lower than baseline value. This can be seen from the plot illustrated in
The plot in
It should also be noted that, while a silicon prism is mentioned as being the type of prism used with the invention, other types of prism may also be used. Any material transparent to the incident light wavelength may be used (e.g. GaAs, InP), but such a material must have an index of refraction sufficiently high that wavevector matching and coupling to the Si film can be achieved.
Regarding the silicon layer, other semiconductor material may be used as the last layer in the sensor element as long as that semiconductor material has a waveguide mode and a high index of refraction comparable to silicon. However, as can be imagined, the ready availability of silicon-on-insulator wafers allows for minimal manufacturing costs.
One possible enhancement to the invention would be to modify the surface of the silicon layer adjacent to the material being sensed. As an example, a pattern may be etched into the silicon layer to enhance the response to the molecular binding. The pattern may be a repeating pattern such as an array of ridge waveguides. Similarly, to improve coupling from the prism to the silicon layer, an etching of a grating may be made on the silicon layer.
A person understanding this invention may now conceive of alternative structures and embodiments or variations of the above all of which are intended to fall within the scope of the invention as defined in the claims that follow.
Filing Document | Filing Date | Country | Kind | 371c Date |
---|---|---|---|---|
PCT/CA2007/001407 | 8/15/2007 | WO | 00 | 6/17/2010 |