MULTIPLEXED PHOTONIC MEMBRANES AND RELATED DETECTION METHODS FOR CHEMICAL AND/OR BIOLOGICAL SENSING APPLICATIONS
Photonic detection systems and methods are shown. A flow through photonic membrane is provided with pores which are distributed along multiple regions. The pores of one region have walls to which a first type of target specific anchor can be attached, while pores of another region have walls to which a second type of target specific anchor can be attached. An additional region of pores without anchors can be provided, so that optical detection occurs differentially. A stack of photonic membranes is also provided. The diameter of the pores of one photonic membrane is larger than the diameter of the pores of another photonic membrane, thus allowing also determination of the size of a target organism flown through the stack of membranes.
The present application claims the priority benefit of U.S. Provisional Application 60/993,740 filed on Sep. 13, 2007, which is incorporated herein by reference in its entirety.
FIELDThe present disclosure relates to photonic membranes. More in particular, it relates to flow through photonic membranes for chemical and/or biological sensing applications and related detection methods.
BACKGROUNDRecently, interest has emerged in label-free optical affinity-based biosensors, which allow to study bio-organisms without fluorescence or radiolabels, and thus dramatically simplify assays. Typically, affinity-based biosensors detect the presence of a target molecule by selective binding to a capture probe. For optical biosensors, binding translates into a change of optical properties, i.e. the complex refractive index or luminescence.
Optical detection methods based on complex refractive index transduction include interferometry in micro and nanofabricated devices, including porous thin films, Bragg reflectors, and microcavities, all of which require an optical measurement system with large beams and sensing areas (about 1 mm2). See E. Chow, A. Grot, L. W. Mirkarimi, M. Sigalas, and G. Girolami, Ultracompact biochemical sensor built with two-dimensional photonic crystal microcavity, Optics Letters 29, 1093 (2004); L. L. Chan, B. T. Cunningham, P. Y. Li, D. Puff, Self-referenced assay method for photonic crystal biosensors: Application to small molecule analytes, Sens. Actuators B 120, 392 (2007); V. S.-Y. Lin, K. Motesharei, K. Motesharei, K.-P. S. Dancil, M. J. Sailor, and M. R. Ghadiri, Science 278, 840 (1997); F. Morhard, J. Pipper, R. Dahint, and M. Grunze, Sens. Actuators B 70, 232 (2000); M. Loncar, A. Scherer, and Y. Qiu, Appl. Phys. Lett. 82, 4648 (2003).
Within this scenario, photonic crystals constitute an emerging alternative technology, due to their powerful light-confinement abilities which would enable local, and therefore, sensitive, refractive index measurements.
Extensive work has been performed during the last fifteen years to build and investigate photonic crystals, the optical analogues to electronic semiconductors. In semiconductors electrons propagate in a periodic potential, which originates from the atomic lattice. This modifies the dispersion of free electrons and opens a bandgap in the energy diagram, as shown in
In particular,
Photonic crystals are materials built to present a periodic variation of refractive index. The periodicity being of the same order of magnitude as the wavelength of the electromagnetic (EM) waves, these structures exhibit band gaps for photons, as indicated in
Most of these devices are designed with opto-electronic applications in mind and despite a recent step in the bio-sensing direction with blind 1D structures (see Schmidt, B., Alemeida, V., Manolataou, C., Prebel S., & Lipson, M., Nanocavity in a silicon waveguide for ultrasensitive detection, Appl. Phys. Lett. 85, 4854 (2004)), and non-specific chemical detection with blind 2D crystals, no selective chemical or biological detection has ever been reported with a 2D photonic platform (see the previously mentioned paper and also Levine, M. J. et al. Zero-mode waveguides for single molecule analysis at high concentration, Science, 299 (2003)).
The ability to manipulate photonic bandgaps in the crystals by design offers the possibility of engineering highly resonant structures, and therefore high-Q microcavities, which makes photonic crystals attractive candidates for ultra compact, highly sensitive assays. Over a few μm2 sensing area a few fL amount of sample analyte could be studied, providing the backbone for a very dense platform with single organism detection limit (lab-on-chip).
The various schemes and diagrams of
The top scheme of
The darker lines of the two upper center diagrams are data collected after functionalization of the device with TWCP (tetratryptophan ter-cyclo pentane), a molecule that selectively binds lipid A present in the viral coat of Gram(−) bacteria. The lighter lines of the two upper center diagrams are data collected after exposure of the functionalized device to Gram(−) bacteria (right) and Gram(+) bacteria (left). The lines of the two lower diagrams represent the difference between the darker and lighter lines discussed above and allow to measure the spectral shift in photonic band gap resulting from the increase of refractive index in the DBRs upon binding of bacteria. The data is summarized in the bottom table of
Although it provides a proof of concept for the use of chemically functionalized 1D photonic crystals for bio-organism detection, the device presented on
Functionalized silicon membranes were fabricated by electrochemistry and their ability demonstrated to selectively capture simulated bio-organisms. A photonic membrane can be defined as a photonic crystal formed of a periodic array of through-holes fabricated in a free-standing membrane waveguide, where the refractive index of the membrane material is larger than the refractive index of the surrounding air or liquid. A photonic membrane provides strong confinement of light both along and perpendicularly to the plane of the membrane. In particular,
Through channels or pores with diameters ranging from a few hundreds of nanometers to many microns were etched on pre-patterned silicon substrates and covalently functionalized with antibodies (see Létant, S. E., Hart, B. R., Kane, S. R., Hadi, M., Shields, S. M. & Reynolds, J. G. Enzyme immobilization on porous silicon surfaces, Adv. Mat. 16, 689 (2004) and Hart, B. R., Létant S. E. et al. New method for attachment of biomolecules to porous silicon, Chem. Comm. 3, 322 (2003)), in order to add chemical specificity to size selectivity. See also U.S. Pat. No. 7,155,076, incorporated herein by reference in its entirety.
The ability of the functionalized membranes to capture simulated bio-organisms was then successfully tested (as shown in
According to a first aspect, a photonic detection system is provided, comprising: a photonic membrane with through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached; an optical input to the photonic membrane; and an optical output detecting arrangement connected with the photonic membrane, wherein the through pores are distributed on the photonic membrane along multiple regions of through pores, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached, and so on.
According to a second aspect, a photonic detection system is provided, comprising: a plurality of photonic membranes stacked on each other, each photonic membrane having through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached; an optical input arrangement to the plurality of photonic membranes; and an optical output detecting arrangement connected with the photonic membranes, wherein the through pores are distributed on each of the photonic membranes along multiple regions of through pores, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached and so on, and a diameter of the through pores of the first photonic membrane is larger than a diameter of the through pores of the second photonic membrane, the diameter of the through pores of the second photonic membrane is larger than a diameter of the through pores of a third photonic membrane and so on.
According to a third aspect, a method of detecting target organisms of an analyte comprising non-target organisms and said target organisms is provided, the method comprising: flowing the analyte through a photonic membrane with through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached, the through pores being distributed on the photonic membrane along multiple regions, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached, and so on; and photonically detecting said target organisms through binding of said target organisms with one or more of said chemical or biological target specific anchor.
According to a fourth aspect, a method of detecting target organisms of an analyte comprising non-target organisms and said target organisms is provided, the method comprising: flowing the analyte through a plurality of photonic membranes stacked on each other, each photonic membrane having through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached, the through pores being distributed on of each the photonic membranes along multiple regions of through pores, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached and so on, wherein a diameter of the through pores of the first photonic membrane is larger than a diameter of the through pores of the second photonic membrane, the diameter of the through pores of the second photonic membrane is larger than a diameter of the through pores of a third photonic membrane and so on; and photonically detecting type of said target organisms through binding of said target organisms with one or more of said chemical or biological target specific anchors, and size of said target organisms through the diameter of the one or more pores associated with said one or more anchors.
According to a fifth aspect, a flow through photonic membrane is provided, comprising: through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached, the through pores distributed on the photonic membrane along multiple regions of through pores, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached, and so on.
Further embodiments of the present disclosure can be found in the written specification, drawings and claims of the present application.
According to an embodiment of the present application, Applicants show a 2D photonic crystal, in particular a 2D flow through photonic membrane, in which the refractive index periodicity is constituted of alternating layers of bulk silicon and air (well defined channels). This design leads to a dramatic reduction of the detection limit since the device is sensitive to local changes of refractive index in each channel (by opposition to the effective refractive index change that has to occur across the entire porous silicon structure shown on
The teachings of the present disclosure provide a viable solution to technology gaps in the Biological Warfare (BW) and Chemical Warfare (CW) detection areas. A real-time capability has been identified to detect, identify, characterize, locate, and warn against BW (and CW) agent threats. The proposed devices and methods combine collection, concentration, and detection of differently sized bio-organisms or chemical agents onto a single platform: an integrated system of photonic waveguiding silicon membranes.
The approach of the present disclosure eliminates the current spatial and temporal disconnection between on-field sample collection and laboratory analysis. Because of the strong light-confinement properties of photonic crystal microcavities (high quality factor, or high-Q), it is expected that detection is allowed down to a single organism and will only require a very small sensing area (˜10-100 μm2) and very small amounts of sample (˜1-10 fL). In addition, since the membrane allows flow-through, Applicants also expect that much larger volumes of analyte can be accommodated when available, and even further promoted by a three-dimensional staggered filtration architecture. A further advantage of the flow-through geometry according to the present disclosure is that it improves the binding probability of the target organism to the molecular probes anchored on the pore walls.
In particular, during the analyte flow (70), light is input (80) into the photonic membrane (10) and output (90) from the photonic membrane (10). The output light (90) is detected through a detector (100) and the results evaluated through a data processing system (110). In particular, as shown in the bottom graph of
As shown in the embodiment of
Similarly to what explained in
With reference to the embodiments of
The transmission of light through the photonic crystal can be recorded before and after binding of the organisms using the end-fire technique described with reference to
The membrane in accordance with the embodiments of
A further embodiment of the present disclosure is shown in
As shown in
In this way, a progression of pore diameters, starting, for example, from large bacteria-sized channels and progressively reduced, for example, to virus size, is obtained. Such geometry also reduces the clogging probability while allowing multiplexing. Moreover, the size of the organism can be determined vertically and chemical composition of the coat can be detected horizontally (for each size range, various antibodies can be anchored on parallel channel rows). The structure of
With reference to the embodiments of the previous figures, the applicants believe that no more than 10 pores are necessary in each row to open the photonic band gap. According to an embodiment of the present disclosure, a possible number of pores would be 5-10 per line. The number of pores per line is subject to competing conditions: on one side more pores provide a long range periodicity and, therefore, a well defined photonic band gap; on the other side, more pores also imply a longer distance for the photons to travel and, therefore, a higher probability of losses. Point defects can also be inserted in each row to engineer and control modes in the photonic band gap.
If a bio-organism (represented by the bead (850) in
The wavelength of the light used in the embodiments of the previous figures can also be an ultraviolet (UV) or near-infrared (IR) frequency.
Each photonic waveguide slab or membrane can be made, for example, of silicon or other materials such as SiONy, SiOx, SiC, GaN, PbTe and, more generally, oxides, III-V or II-VI semiconductors, and polymers. Various interrogation wavelengths can be used across the device, as already explained above. In particular, smaller pore sizes mean a photonic bandgap at a lower wavelength. As also mentioned before, a broad source can be used to record the entire band gap transmission, while a single wavelength can be used to interrogate specific modes in the photonic band gap. The device can be used for biological (bacteria, viruses, toxin) and chemical sensing.
Future applications can also include the generation of fingerprints for the detection and classification of non-traditional agents and emerging threat agents. In particular, the system according to the present disclosure could be trained like artificial noses. In other words, a very broad set of known organisms would be tested and the corresponding data stored in a database. When an unknown sample is processed by the membrane stack, the data can be analyzed via PCA (Principal Component Analysis) and compared to the database. The data from the entire device stack (all the lines, from all the stacks) can be seen as a fingerprint.
Accordingly, what has been shown are photonic membranes for detection of biological and/or chemical organisms and related detection methods. While the membranes and methods have been described by means of specific embodiments and applications thereof, it is understood that numerous modifications and variations could be made thereto by those skilled in the art without departing from the spirit and scope of the disclosure. It is therefore to be understood that within the scope of the claims, the disclosure may be practiced otherwise than as specifically described herein.
Claims
1. A photonic detection system comprising:
- a photonic membrane with through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached;
- an optical input to the photonic membrane; and
- an optical output detecting arrangement connected with the photonic membrane,
- wherein the through pores are distributed on the photonic membrane along multiple regions of through pores, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached, and so on.
2. The system of claim 1, wherein the optical input to the photonic membrane comprises a plurality of optical input lines, one for each region of through pores.
3. The system of claim 1, wherein the optical output detecting arrangement comprises a plurality of detectors, one for each region of through pores.
4. The system of claim 1, wherein the photonic membrane comprises an additional region of through pores to which no chemical or biological target specific anchors are attached.
5. The system of claim 4, wherein measurement of a detection output of the photonic detection system occurs differentially, by subtraction of a detection output of the additional region of through pores from a detection output of each region of through pores.
6. The system of claim 1, wherein the optical input is a laser light.
7. The system of claim 1, wherein the optical detecting arrangement is a multichannel detector.
8. The system of claim 1, wherein the optical detecting arrangement is connected with a processing unit downstream of the photonic membrane.
9. The system of claim 8, wherein the processing unit is a portable computer.
10. The system of claim 1, wherein the photonic membrane is a silicon photonic membrane.
11. The system of claim 1, wherein the multiple regions of through pores are shaped differently from each other.
12. The system of claim 1, wherein each region of through pores is selected from the group consisting of: a line of through pores with a ridge geometry, a perfect photonic crystal comprising an array of through pores, and a photonic crystal comprising an array of through pores and a defect.
13. The system of claim 12, wherein the defect is selected from the group consisting of: a pore with a different diameter or shape than the remaining through pores of the array, and a removed pore.
14. A photonic detection system comprising:
- a plurality of photonic membranes stacked on each other, each photonic membrane having through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached;
- an optical input arrangement to the plurality of photonic membranes; and
- an optical output detecting arrangement connected with the photonic membranes,
- wherein
- the through pores are distributed on each of the photonic membranes along multiple regions of through pores, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached and so on, and
- a diameter of the through pores of a first photonic membrane is larger than a diameter of the through pores of a second photonic membrane, the diameter of the through pores of the second photonic membrane is larger than a diameter of the through pores of a third photonic membrane and so on.
15. The system of claim 14, wherein a first region of through pores of the first photonic membrane is in spatial correspondence with a first region of through pores of the second photonic membrane, a second region of through pores of the first photonic membrane is in spatial correspondence with a second region of through pores of the second photonic membrane and so on.
16. The system of claim 14, wherein the photonic membranes are vertically stacked on each other.
17. The system of claim 14, wherein the photonic membranes are vertically stacked on each other, the first region of through pores of the first photonic membrane being vertically aligned with the first region of through pores of the second photonic membrane, the second region of through pores of the first photonic membrane being vertically aligned with the second region of through pores of the second photonic membrane and so on.
18. The system of claim 14, wherein the photonic membranes are silicon photonic membranes.
19. The system of claim 14, wherein the multiple regions of through pores are shaped differently from each other.
20. The system of claim 14, wherein each region of through pores is selected from the group consisting of: a line of through pores with a ridge geometry, a perfect photonic crystal comprising an array of through pores, and a photonic crystal comprising an array of through pores and a defect.
21. The system of claim 20, wherein the defect is selected from the group consisting of: a pore with a different diameter or shape than the remaining through pores of the array, and a removed pore.
22. A method of detecting target organisms of an analyte comprising non-target organisms and said target organisms, the method comprising:
- flowing the analyte through a photonic membrane with through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached, the through pores being distributed on the photonic membrane along multiple regions, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached, and so on; and
- photonically detecting said target organisms through binding of said target organisms with one or more of said chemical or biological target specific anchor.
23. The method of claim 22, wherein said photonically detecting is carried out through coupling of light into the photonic membrane.
24. The method of claim 22, wherein the photonic membrane comprises an additional region of through pores to which no chemical or biological target specific anchors are attached and wherein said photonically detecting occurs differentially, by subtraction of a detection signal of the additional region of through pores from a detection signal of each region of through pores.
25. The method of claim 22, wherein through holes on the photonic membrane are obtained through focused ion beam (FIB) drilling.
26. The method of claim 22, wherein the multiple regions of through pores are shaped differently from each other.
27. The method of claim 22, wherein each region of through pores is selected from the group consisting of: a line of through pores with a ridge geometry, a perfect photonic crystal comprising an array of through pores, and a photonic crystal comprising an array of through pores and a defect.
28. The method of claim 27, wherein the defect is selected from the group consisting of: a pore with a different diameter or shape than the remaining through pores of the array, and a removed pore.
29. A method of detecting target organisms of an analyte comprising non-target organisms and said target organisms, the method comprising:
- flowing the analyte through a plurality of photonic membranes stacked on each other, each photonic membrane having through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached, the through pores being distributed on each of the photonic membranes along multiple regions of through pores, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached and so on, wherein a diameter of the through pores of a first photonic membrane is larger than a diameter of the through pores of a second photonic membrane, the diameter of the through pores of the second photonic membrane is larger than a diameter of the through pores of a third photonic membrane and so on; and
- photonically detecting type of said target organisms through binding of said target organisms with one or more of said chemical or biological target specific anchors, and size of said target organisms through the diameter of the one or more pores associated with said one or more anchors.
30. The method of claim 29, wherein a first region of through pores of the first photonic membrane is in spatial correspondence with a first region of through pores of the second photonic membrane, a second region of through pores of the first photonic membrane is in spatial correspondence with a second region of through pores of the second photonic membrane and so on.
31. The method of claim 29, wherein said photonically detecting is carried out through coupling of light into the photonic membranes.
32. The method of claim 29, wherein each photonic membrane comprises an additional region of through pores to which no chemical or biological target specific anchors are attached and wherein said photonically detecting occurs differentially, by subtraction of a detection signal of the additional region of through pores from a detection signal of each region of through pores of said each photonic membrane.
33. The method of claim 29, wherein the pores are obtained through focused ion beam (FIB) drilling.
34. A flow through photonic membrane comprising:
- through pores, the through pores having inner walls to which chemical or biological target specific anchors are adapted to be attached, the through pores distributed on the photonic membrane along multiple regions of through pores, through pores pertaining to a first region having inner walls to which a first type of chemical or biological target specific anchor is attached, through pores pertaining to a second region having inner walls to which a second type of chemical or biological target specific anchor is attached, and so on.
35. The photonic membrane of claim 34, wherein the multiple regions of through pores are shaped differently from each other.
36. The photonic membrane of claim 34, wherein each region of through pores is selected from the group consisting of: a line of through pores with a ridge geometry, a perfect photonic crystal comprising an array of through pores, and a photonic crystal comprising an array of through pores and a defect.
37. The photonic membrane of claim 36, wherein the defect is selected from the group consisting of: a pore with a different diameter or shape than the remaining through pores of the array, and a removed pore.
38. A method of using the photonic membrane of claim 34, comprising:
- inputting a white light source to the photonic membrane; and
- feeding a corresponding output of the photonic membrane to a spectrometer arrangement.
39. A method of using the photonic membrane of claim 34, comprising:
- inputting a monochromatic light to the photonic membrane; and
- feeding a corresponding output of the photonic membrane to a detecting arrangement.
Type: Application
Filed: Sep 8, 2008
Publication Date: Oct 1, 2009
Inventors: Sonia E. LETANT (Livermore, CA), Tiziana C. Bond (Livermore, CA)
Application Number: 12/206,337
International Classification: G01N 21/01 (20060101);