Nanotechnology has advanced and played a pivotal role in today's society. Plasmonic sensing has demonstrated unprecedented detection reliability and resolution in a compact form factor. Traditional plasmonic sensors leverage bio-functionalized metallic grating structures whose frequency response in transmission or reflection changes according to a presence of targeted biomarkers.
Existing biosensing setups require bulky measurement equipment to couple light to and from sensors for excitation and detection. In parallel with the development of plasmonic nano-sensing, the nanoscale electromagnetic communication community has been using plasmonic structures to transmit information at the nanoscale efficiently.
The inventors have recognized that these two realms of sensing and communication may be co-implemented in embodiments in a manner to produce advantages over either one alone and to enable nanoscale biosensing with simultaneous communication in order to enable both technologies to the implanted within a living being within the same biosensor. Disclosed herein are embodiments that take implement joint nanoscale communication and biosensing enabled by biosensing nano-antennas. Sensing nano-nodes can communicate from nano-node to nano-node for intra-body networks and from nano-node to a wearable device. In addition, edge computing and networking can be leveraged in order to process and transmit the sensing information to the cloud. This has the further advantage of enabling accurate diagnosis and reducing load on the medical testing infrastructure.
Disclosed herein is a modeling of the changes in frequency response of a bio-functionalized plasmonic nano-antenna when exposed to different biomarkers. Further disclosed herein is a chirp-spread spectrum excitation and detection method that can be implemented in the embodiments as one way of enabling simultaneous communication and sensing at the nanoscale. A data-driven human tissue model of communication through human tissue is included. Numerical results to demonstrate superior performance of embodiments are also disclosed.
In one particular embodiment, a biosensor includes:
Among other optional features, the biosensor can further optionally and advantageously include a detector at the biosensor, the detector configured to detect the emitted light and to provide an output indicative of the receipt or nonreceipt of the biomarker by the bio-functionalized element. The combination of the light source and the plasmonic nano-antenna optionally and advantageously can be further configured to encode the output indicative of the receipt or nonreceipt of the biomarker into the optical communication signal.
The light source, the plasmonic nano-antenna, and the detector optionally and advantageously mounted onto a common chip.
In another embodiment, a communication node includes
The communication node can further include a bio-functionalized element joined to the plasmonic nano-antenna and configured to receive a biomarker if the biomarker is available, the bio-functionalized element configured to effect a change in the spectral signature as a function of receipt or nonreceipt of the biomarker.
The communication node can further include a detector configured to detect the emitted light exhibiting the spectral signature and provide an output indicative of whether the biomarker is received based on the spectral signature.
The communication node can further include a modulator configured to modulate the source light with a modulation as a function of the output indicative of whether the biomarker is received, the modulation causing the output indicative of whether the biomarker is received to be encoded into the communication signal.
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The foregoing will be apparent from the following more particular description of example embodiments, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments.
A description of example embodiments follows.
The light source and plasmon nano-antenna are “at” the biosensor 100, indicating that they are part of the same implantable biosensor forming one biosensor unit. In one example, the light source 102 and plasmonic nano-antenna 110 can be encompassed by, or held within, a biocompatible housing of the biosensor, as illustrated in example
The biosensor 100 is configured to be implanted in a living being 108, as illustrated at the left of
The light source 102 is configured to generate source light 104 that has a source light spectrum, such as the example source light spectrum 106 illustrated in
The plasmonic nano-antenna 110 is optically coupled to the light source 102 in a manner such that the plasmonic nano-antenna 110 is configured to receive the source light 104. The plasmonic nano-antenna 110 is further configured to emit light 112 therefrom, with the emitted light 112 exhibiting a spectral signature of the plasmonic nano-antenna. A bio-functionalized element 116 is joined to the plasmonic nano-antenna and configured to receive a biomarker 118 (e.g., a disease biomarker) if the biomarker is or becomes available (sufficiently proximal to) the bio-functionalized element 116. Bio-functionalized elements are described further hereinafter, by way of example, in connection with
The bio-functionalized element 116 is configured to effect a change in the spectral signature as a function of receipt or nonreceipt of the biomarker 118. Receipt of the biomarker 118 is illustrated schematically via an arrow 120. An example spectral signature 114a of the emitted light 112 is illustrated in
A combination of the light source 102 and the plasmonic nano-antenna 110 is configured to encode an optical communication signal into the emitted light 112. Transmission of the optical communication signal is illustrated in
In one example, the optical communications signal encoding can include an encoded indication of whether the biomarker 118 is received by the bio functionalized element 116 (e.g., indicating whether a disease is present if the biomarker is a disease biomarker). However, any other type of information or data that are desired to be communicated from the biosensor 100 to the communication node 126 can also be encoded into the emitted light 112 additionally or alternatively. This option is represented and described hereinafter in part in connection with the optional “other data in” 164 illustrated in
The emitted light 112 should be understood broadly to include any light, such as covering any wavelength or frequency range of the source light 104, that emanates from the plasmonic nano-antenna 110 as the light 104 is received by the plasmonic nano-antenna 110, and as changed or not changed by receipt or nonreceipt of the biomarker 118 by the bio-functionalized element 116. In one example, illustrated in
In some embodiments, different components of the emitted light 112 can have different spectral compositions. In one example, emitted light 112 that is reflected by the plasmonic nano-antenna 110 can have a power peak at a resonant frequency of the plasmonic nano-antenna 110, while emitted light 112 that is transmitted includes a valley in power spectral density at the same frequency position as the peak in the reflected light. In other embodiments, emitted light 112 that is transmitted through the plasmonic nano-antenna 110 can be used both for the optical communication signal transmission 124 and for detection by the detector 128.
As part of the optional features of the biosensor 100, the detector 128 provides an output 132 that is indicative of the receipt or nonreceipt of the biomarker 118 by the bio-functionalized element 116. This can be a Boolean value or can be represented by more complex data, such as a representation of the spectral signature of the emitted light, for example. The modulator 134 is configured to receive the output 132, as well as “other data in,” represented by the arrow 164. The modulator 134 provides modulation, represented at arrow 136, of the light source 102. Combined with the plasmonic nano-antenna, this is further configured to encode the output 132 indicative of the receipt or nonreceipt of the biomarker into the optical communication signal 124.
The modulator 134 effects modulation in the source light, resulting in the corresponding modulation being exhibited in the emitted light 112. The combination of the light source 102 and the plasmonic nano-antenna 110 are thereby configured to encode the optical communication signal into the emitted light 112 via the corresponding modulation 136 exhibited in the emitted light. As described in connection with
The bio-functionalized elements 116 can include a dielectric surface having nanosphere or microsphere particles situated thereon, as illustrated in example
As illustrated in
The plasmonic nano-antenna 110 can include a gold or gold alloy layer situated between dielectric layers, as illustrated in
Certain of these and additional features of embodiments are described hereinafter in the following order. In Sec. I, an introduction to the further subject matter, and context for this, is provided. Sec. II presents relevant related work focusing on the human tissue channel model for optical signals, plasmonic biosensors, bio-functionalization and joint communication and sensing. Sec. III presents a design of an embodiment optical nano-antenna. Sec. IV provides data evaluating performance of the designed embodiment nano-patch antenna as a biosensor. Sec. V presents a design of the chirp waveform signal to extract the sensing information and carry the data in certain embodiments. Sec. VI presents a channel model for understanding the sensor-sensor and sensor-wearable device interactions in certain embodiments. Sec. VII presents one detection mechanism that can leverage the chirp waveform and the antenna response for performing sensing detection along with joint communication packet decoding in certain embodiments. Sec. VIII describes communication link analysis for different scenarios and model factors such as channel and noise on the received signal and bit error rate. Sec. IX presents numerical analysis results showcasing results from the analytical and numerical models, and in Sec. X, highlights of key advantages and study results for embodiments are presented.
With technological advances in science and technology, we are in the most-connected era of human society history ever. We live in a society where information travels at the speed of light, and traveling is easier than it ever has been in history. In such a dynamic paradigm, early pathogen detection and diagnosis are the key to defer the next pandemic in such a connected world. Traditionally, pathogen detection has been performed by using several sensing mechanisms such as color-changing chemical titration, microscopy, spectrometry, and recent RNA/DNA-based detection methods.
In parallel to these techniques, plasmonic sensing is an upcoming sensing technology that promises unprecedented accuracy for biomarker detection. Plasmonic sensing leverages molecular interactions at the nanoscale and bridges that with the macro world using light as an information carrier. Light, i.e., electromagnetic radiation in the optical spectrum, is utilized because its small wavelength enables molecular scale interactions with matter. Plasmonic nanostructures are designed to couple the incident light into plasmonic waves on metallic-dielectric interfaces. These plasmonic surface waves are sensitive to the surface structure properties and are therefore leveraged for sensing. The surface is made biomarker selective using molecular engineering where a bio-functionalized molecular layer is deposited on this plasmonic surface. The bio-functionalized layer binds only to the biomarker of interest and offers very high selectivity. This unprecedented selectivity allows for accurate detection at an ultra-low concentration.
Despite the unique capabilities of plasmonic sensors for biomarker detection and selectivity, currently, bulky test equipment is needed to interrogate the sensors, limiting their practical application. In parallel to these advances in sensing technology, nano-structural engineering and nano-photonic designs are also advancing the optical technology to nanoscale applications. In the last decade, lasing devices with ultra-small footprints, on-chip waveguides, plasmonic waveguides, power-splitters, phase shifters, nano-antennas, and metamaterials have enabled unprecedented nano-photonic advancements. While most of these technologies aim at solving communication bottlenecks by enabling ultra-compact broadband communication, these can be tailored to support nanoscale sensing applications.
Besides light-based nano-sensing, nanoscale communication has become an emerging field that can be leveraged to communicate intrabody nanomachine to nanomachine or implanted nano-machine to wearable. For such communications, different technologies are proposed such as galvanic coupling, ultrasound waves, electromagnetic waves in radio frequency band, TeraHertz band, and optical band, as well as molecular communications. Together, the aim has been to enable an Internet of Nano-Bio Things that bridges the macro world in which we live with the biological world inside our body. This opens the door to unprecedentedly precise sensing of disease biomarkers and real-time recovery monitoring and, ultimately, the next wave in healthcare technology that bridges the nano-bio scale with the power of cloud computing through edge networks. Such systems promise timely diagnosis, real-time monitoring and will play a key role in early detection of infectious diseases and mitigating future pandemics. Nevertheless, while these technologies provide a roadmap for the future of Internet of Nano-Bio Things, the technological bridges that can translate these models into real nano-device designs have been missing.
Disclosed herein are biosensors and communication nodes that can include plasmonic nano-antennas that can also work as bio-functionalized sensors to bridge the gap of the nano-sensing device and nanoscale intra-body communications.
All of these features and others are situated on a common chip 474 to achieve optical integration. Part of this integration is provided by a light guide 446. The light guide 446 conveys source light from the light source 402 to the nano-sensing antenna 210. Emitted light from the nano-sensing antenna 210 varies according to a spectral signature of the nano-sensing antenna 210, depending on whether a disease biomarker 418 is received at the bio-functionalized layer 210 that is joined to the plasmonic nano-antenna 210.
The emitted light that is reflected back from the nano sensing antenna 210 is further received at the processing and memory unit 402 via the light guide 446. The processing and memory unit 402 provides not only a light source, such as the light source 102 in
With the light source 402, the plasmonic nano-antenna 210, the detector present in the processing and memory unit 402, and other components all mounted on the common chip 472, a high degree of integration and compactness is provided. With the plasmonic nano-antenna optically coupled to the light source via the light guide 446 on the common chip, the detector is further configured to receive the emitted light (not shown in
The system 400 of
Research groups have previously modeled human tissue as a channel for optical signal propagation. These works rely on experimental data and the spectrometric analysis of tissue types such as skin, blood, adipose, muscle, brain tissue, and melanin concentrations. While many of these measured properties help model human tissues to some degree, in reality these models have large variance and any multi-layer or bulk tissue model without some modification cannot perfectly fit all humans. This is because the composition of human body varies from person to person. However, a fair approximation can be made to guide the engineering design with factors such as layer thickness and concentration. The concentrations of factors such as fat, melanin content, and blood concentration affect the optical signal propagation. For the special case of optical communication at nanoscale, along with these factors, non-homogeneity of the tissues and cellular composition also affects the signal propagation making it even more challenging to predict the response. Some works have attempted to create models that aim to target such nanoscale communication links for cell-cell or nanomachine-cell interactions.
Plasmonic biosensors have been an active area of research in last decade and there has been a myriad of advances made in this field. Plasmonic biosensing relies on plasmon polariton waves which can be excited using a prism and coupling the light in reflection from the sensor. The surface of a plasmonic sensor is coated with bio-functionalized layer that binds to target molecule and changes structure resonance. This effect is then detected in reflection or transmittance to perform sensing. Plasmonic biosensing can be performed using different mechanisms: Surface plasmon resonance (SPR) sensing, localized surface plasmon resonance (LSPR) biosensing, Chiral plasmonic biosensing, Magnetoplasmonic biosensing, and Quantum plasmonic biosensing.
The LSPR biosensing is done using subwavelength particles, which, due to the small size, are more sensitive to their surrounding media properties. Traditionally, they have been used to enhance the spectroscopic measurements such as in surface-enhanced infrared absorption spectroscopy, surface-enhanced Raman scattering, surface-enhanced fluorescence, and by detecting a shift in absorption spectra (sensitive to surrounding molecules).
Chiral plasmonic biosensing relies on the fact that chiral symmetry causes different absorption for right-hand circularly polarized light and left-hand circularly polarized light. This difference can be leveraged at the plasmonic level to identify the mechanisms of chiral bioactivity in proteins. Chiral plasmonic has, therefore, become an active area of research to develop chiral sensitive plasmonic structures for sensing in visible and NIR region.
Magnetoplasmonics biosensing relies on magnetic nanoparticles and magneto-optical structures to amplify surface plasmon polariton waves. These merged effects of plasmonic with magneto-optics are called magnetoplasmonics. They have gained their popularity for in-vitro sensing and bio-imaging applications.
Quantum plasmonic biosensing tries to overcome the fundamental limit of plasmonic waves carrying information. By using the quantum properties of light, such as quantum correlation, and shielding, the information carried from the noise floor is defined by the shot-noise limit defined by the Heisenberg uncertainty principle. In addition to these types, there have been demonstrations of sensing based on functionalized graphene nanoribbon-based biosensors, bio-functionalized optical waveguide-based plasmonics sensors and bio-functionalized field effect transistor channel biosensors that leverage plasmonics to perform sensing.
Plasmonic biosensors are sensitive to their surrounding layers, and to make them sensitive to a particular biomarker, they need to be coated with a bio-functionalized layer. The binding process results in a change of physical properties such as refractive index, conductivity, or pH value, among others. These changes influence the resonance frequency of the SPR sensor. The successful coating of an SPR sensor with a bio-functionalized layer requires two main components, namely, a primer layer and a bio-functionalized layer. The primer binds to the metal surface of the sensor and allows the biomarker selective coating to bind reliably on the sensor.
Based on their type of binding, sensors can be classified into four categories: DNA-, immuno-, cell-, antigen- and imprinting-based sensors. DNA-based sensing lever-ages single-stranded DNA (ssDNA) and its affinity to bind with the virus. A layer of ssDNA with preserved reactivity towards the host-virus is deposited on the SPR. Such ssDNA layer is carefully designed to be stable and relies on nucleic acid hybridization. Peptide nucleic acids, which are structurally similar to DNA, have also proved to be a promising candidate for DNA detection.
Immunosensors rely on using the antigens created by the bodies in response to the virus for detection. These antigens have a higher affinity for the virus proteins and thus bind with them, similar to a lock-key mechanism. Such binding results in the change of the structural properties of the surface layer, which changes the response of the SPR sensor, thus allowing for the detection by an optical signal transmitted or reflected by the sensor. To reduce dependency on the immune-generated antigens, active research is going on to develop DNA and peptide aptamers that resemble immune-generated antigens, which have been demonstrated for the detection of viruses. Antigen-based sensors work on the principle of coating the surface with a virus, and when the antigens come in contact with the surface, they change the surface properties. For testing such sensors, antigens are extracted from an infected person's serum. These sensors are limited by the concentration of antigens produced by the person at different stages of infection. These types of sensors are currently limited to out-of-body testing in laboratory setups.
Cell-based sensors cover the surface of the sensor with the host cells. When the virus attaches and infects the cell, it causes the changes, thus providing the ability to analyze cytopathic effects. These sensors provide an alternative to studying viral infections other than hosts or animals.
Imprinting-based sensors rely on using the molecular imprinted polymers, which are synthetically designed to provide complimentary vacancies in the polymer matrix that allows for the deposition of the target antibody or virus on the surface. These perform similar to the biological methods of detection but improve on increasing reliability and function in harsh operating environments with re-usability and reduced cost.
Biosensors can be impacted by other elements besides their target biomarker. More specifically, while they might not chemically react, other blood components, including red and white blood cells and platelets, might obstruct the implant. Correspondingly, sensor defouling and reusability are currently at the center of several studies, and multiple different methods have been proposed, from ultrasonic cleaning to electrochemical defouling.
Joint communication and sensing have recently gained popularity in the context of 5G and even 6G networks. Mainly, in joint communications and sensing systems, the same hardware, the same spectrum, and ultimately, the same signals are utilized to both carry information from the transmitter to the receiver while performing radar, i.e., extracting information from the channel itself. These types of systems leverage properties of signal propagation for multipurpose applications. However, other sensing methods utilize the communication channel changes for sensing, such as optical fiber-based earthquake detection and waveguide-based optical sensing. With some known properties about the channel, they all rely on the spectrographic properties of the molecules composing the channel and try to predict the presence of a certain molecule based on its band of absorption. These systems rely on a relatively wide band transmitter and a sensitive detector that can sweep across the band of interest accurately for valid detection signals. Traditionally, these sensing measurements were performed by spectrometers, but with advances in device technology and the access to low-cost high-quality sources and detectors widely available for communications, these measurements can be performed using the communication equipment.
Optical nano-antennas covering the 1-770 THz frequency range in some embodiments are functionally similar in some respects to their radio-frequency counterparts. They rely on the electromagnetic (EM) wave propagation length and the resonating structural parameters. However, materials such as metals, which are perfect electric conductors at radio frequencies, do not behave as perfect electric conductors at optical frequencies. These material properties influence the EM wave propagation inside the material and thus the overall geometry of the resonating structure.
At optical frequencies, metals exhibit complex frequency-dependent conductivity. This complex conductivity arises/originates from the plasmon polariton waves on metal-dielectric interfaces. Plasmon waves are surface waves that exist in the electron cloud of the metal present on the metal-dielectric interface. These oscillations and their effect on the permittivity of the metal can be represented by the Drude-Lorentz model as:
where εm is the permittivity of the metal, ωp is the plasma frequency of the material, τd is the electron relaxation time, εm (ϑ) is the high frequency dielectric constant and ω=2πf is the angular frequency.
Using this complex conductivity model, the propagation wave vector kspp can be calculated accounting for the dispersion along the structure as per equation:
where k0=ω/c is the free space vector, β stands for the complex propagation constant parallel to the surface, ε1 and ε3 are the permittivity of the layers surrounding the metal sheet, and εm is the permittivity of the metal as described in (1). Using kspp, we can calculate the plasmonic wavelength using the relation:
At optical frequencies, λspp governs the antenna design equations instead of the free space wavelength.
Therefore, it is established that the resonating frequency of our antenna is sensitive to not only the structure length but also to the surrounding material properties. This property can be harnessed for sensing. Sec. IV presents further details on the performance of such a plasmonic antenna as a sensor.
Patch antennas have become a popular choice for design in modern wireless applications. One of the main advantages a patch antenna offers is its flat design which makes it suitable to be produced on a mass scale with reliable manufacturing processes such as integration with printed circuits. Even at the nanoscale, flat designs allow for easier fabrication by using techniques such as metal deposition, masking, and etching.
A patch antenna usually includes three main components, a meticulously designed resonating patch, a ground plane, and a dielectric material in between the patch and ground plane. The geometry of patch is a deciding factor for its resonating frequency, and for perfect conductors is usually in the range of L>λ0/3 and L<λ0/2, where λ0 is the free-space design wavelength. However, the E-field distribution between ground plane and the patch is affected by the dielectric material properties. Therefore, a patch antenna resonance is highly sensitive to the surrounding dielectric properties. Patch antennas are usually designed to function as broadside radiators, radiating maximum power perpendicular to the antenna plane. However, with a careful selection of excitation mode and design parameters, they can also be designed as end-fire radiators, radiating maximum power in the direction of the antenna plane.
Unlike dipole antennas, there is no closed-form expression to dictate the patch antenna geometry. However, there are models that approximate these dimensions, such as cavity model, but these models rely on assumptions that antenna material is a perfect electric conductor, and the models fail to account for phenomena such as plasmonic waves on the antenna-dielectric surface and Fabry-Perot effect from the patch-ground plane cavity. Due to the complexity of formulating these models analytically, FEM analysis is often used as a standard practice to design and predict patch antenna performance.
The inventors have used finite-element methods (FEM) with COMSOL Multiphysics to design and model patch antennas at optical frequencies. The active antenna element and the ground plane have been modeled with the complex-valued material properties of gold. The dielectric substrate sandwiched between the ground plane and the patch is chosen to be of dielectric constant εr=4 (˜ Dielectric constant of SiO2=3.9). The antenna performance parameter S11 has been utilized as the objective function, parametric sweeps have been performed across antenna length, width, and thickness, parameters illustrated in
A biosensor is basically a transducer that converts one form of bio-signal into another form which can be extracted and analyzed to perform detection. Most existing sensors convert the measured bio-signal into a change in properties such as electric/optical conductance, reflected signal, or chemical binding properties. Localized surface plasmonic sensors can transduce the detection results into a difference in their resonating frequency, which can be read in reflection, transmittance, or conductance. To perform detection, these sensors can be coated with a bio-functionalized layer that binds to the biomarkers of interest. This binding results in a change in their surface properties, which affects the propagation of plasmonic waves on the sensor surface.
Generally, an antenna is designed to resonate at the desired frequency. However, in the case of a plasmonic antenna, this frequency can significantly change based on the properties of its surrounding material. This phenomenon offers an unprecedented way to accurately sense the environment with an existing antenna geometry. By bio-functionalized the antenna itself, when the target biomarker is present, both the electrical properties of the antenna building material and the thickness itself change. By tracking those changes, detection is performed.
Modeling a particular biomarker and the corresponding bio-functionalized layer would require an extensive study of the material properties, which is part of many ongoing works. Meanwhile, to analyze the detection performance of the indicated, preferable designed patch antenna, these effects are modelled in FEM analysis with a parameter sweep, as described in following.
To extract the sensing information from the antenna, a wide-band waveform that spans all the possible resonant frequencies of the antenna when sensing should preferably be used. Considering the limited capabilities of a nanomachine, a frequency-sweeping chirp signal can be advantageously used. The simplest chirp waveform is the linear chirp signal, in which the frequency increases with time (up chirp) or decreases with time (down chirp). Chirp waveforms have been widely used for sensing, as the multi frequencies translate to multi-resolution sensing. Chirp waveforms offer several advantages for communications, such as immunity to channel frequency selectivity.
A chirp signal in time domain is defined as
where ϕ0 is the initial phase of the signal and
where C is the chirp rate/slope and fstart is the starting frequency. For linear chirp signals,
where fstop is the chirp stop frequency and fstart is the chirp start frequency and T is the time of sweep.
When this sweeping chirp signal is transmitted through the antenna, the antenna response is imprinted on it, which can be used for sensing. The power spectral density Pt of the imprinted transmitted signal is given by
where Pchirp is the power spectral density of generated chirp signal and Rant is the antenna input reflection coefficient or S11 parameter and depends on the sensed information, as described in Sec. IV.
To model the communication performance for the proposed joint sensing and communication system effectively, an accurate channel model should be used. For this analysis, two scenarios are considered: A) Nano-sensor to nano-sensor link, and B) Nano-sensor to wearable link. The channel losses can be classified as the combination of the following phenomena:
Reflective loss: This is the result of the refractive index mismatch between the different tissue layers in the body. These losses can be modeled using the following equation:
where n1 and n2 stand for the refractive index of Layer 1 and Layer 2, respectively. The refractive index of different tissue types for the wavelengths λ of interest is summarized in Table II.
Scattering and absorption loss: These losses account for the absorption and scattering from the medium. A general calculation for scattering and absorption losses can be performed using the equation:
where μscr is the scattering coefficient, μobs is absorption coefficient and dis the distance/layer thickness. The absorption and scattering properties (user and Jabs) are compiled from literature. For the 400 nm-2000 nm band, plots of absorption and spreading coefficients for blood (for 98% oxygenated blood), adipose tissue, and skin (for Caucasian skin) are shown in
Spreading loss: This captures the fact that the signal propagates as a wave and spreads into the medium. This can be calculated using the equation:
where d is the distance from the radiation source, D is the directivity gain (D=4π/Ω4), for a point directional source such as a laser emitting with the radiated beam angle θ and ϕ, the directivity D can be expressed as:
Total loss: All the previous losses in dB can be added to obtain the total loss suffered by the signal as:
This total channel loss is frequency dependent and can be used to calculate the channel transfer function (H(f)).
For the sensor-to-sensor channel model, the sensors are assumed to be in different tissues, and thus we can create multiple cases. For the present analysis, presented are analytical calculations for two cases: Blood and Adipose (Fat) tissue.
Case 1 is to imagine the sensors are flowing in the bloodstream, as shown in
In case 1, the channel can be modelled as per the optical properties of blood as shown in
Case 2 is when embodiment biosensors are implanted in the fat layer of the human tissue and there is an adipose fat layer between them, as shown in
For the sensor-to-wearable communication, the bulk tissue layered model should be considered. For this analysis, the bulk tissue can be considered to be a collection of different layers, and collective losses from each layer can be determined. For the multi-layer model, the different thickness of the tissue layer used are as follows: Air gap=1 mm, Skin tissue=1 mm, Adipose tissue=(0.1 mm-5 mm), Blood=0.25 mm.
A generated wideband chirp signal, illustrated in
Instead of using the plotting approach and detecting peak power, embodiments biosensors and communication nodes can incorporate a much easier and less computationally intensive method, as illustrated in
The received signals from the narrowband antennas are then fed to a power comparator 1362. If the power at f0 is greater than the power at f1, it can be deduced that the targeted biomarker is absent. However, if the power received at f1 is greater than the power at f0, then the conclusion is that the targeted biomarker is present. According, the detector 1328 uses multiple antenna elements and a power comparator setup similar to those proposed in cooperative spectroscopy. In this manner, calculating sensing output in a nanomachine with the detector 1328 can be facilitated and simplified very advantageously.
With all the building blocks already defined, the communication link is modeled as follows.
A chirp signal is generated as per (7) and radiated by the antenna. Antenna reflection coefficient can be used to derive the antenna transfer function Hant(f) and transmitted signal can be as Xtransmit(f)=X(f) Hant (f), where X(f) is the frequency domain representation of x(t). The power of transmitted signal can be calculated using (10).
The primary channel for the communication link is computed from the human tissue layers model. The total losses are computed using (15). For the bit error rate (BER) analysis, one can focus on the wearable-to-sensor channel shown in
Thus, received signal xr(t) can be calculated by accounting for the frequency-selective channel response.
At the receiver, to maximize the detection, two matched filters may be used, one for the up-chirp and one for the down-chirp. The impulse response of an ideal matched filter is given by h(t)=xr(τ−t), where xr(t) is the received signal at receiver. For the formulation of BER the noise added to the signal can be accounted for, and this can be represented as y(t)=xr(t)+n(t), where n(t) is the additive white Gaussian noise. To perform the detection, the received signal is then multiplied with the corresponding up-chirp s1(t) and down-chirp s0(t) signal to produce detector outputs.
Comparing M0 and M1, the detected bit can be identified. If M0>M1, the detected bit is “0,” and if M0<M1, the detected bit is “1.” The cross-correlation coefficient ρ between up-chirp and down-chirp is defined as:
where Eb is the energy per bit. For a standard chirp signal probability of error can be analytically expressed as:
where N0 is noise power spectral density. The relation between signal to noise ratio (SNR), Eb and N0 is given by:
where Rb is the bit rate, B is bandwidth, Eb is the energy per bit and N0 is power spectral density of noise.
The chirp in the source light can be up or down in frequency with time. Accordingly, a modulator such as the modulator 134 can be configured to cause the light source to output the source light as chirp-up and chirp-down pulses.
The generated chirp signal is then transmitted through the plasmonic nano-antenna of an embodiment biosensor. To account for the effect of the antenna response on the transmitted chirp, the transfer function of the antenna can be calculated, and the power of the transmitted signal can be calculated using (10). The transmitted signal power is plotted in
To perform detection successfully from the received signal, the power is computed and the power spectrum of the received signal is plotted. As shown in
For joint sensing and communication analysis, the up-chip transmitted signal is modeled as bit 1 and down-chirp as bit 0. Using this symbol encoding, the data packet is encoded and transmitted.
In the manner illustrated by
For the performance analysis of this proposed joint communication and sensing system, BER analysis simulation was performed with 10,000 bits. This was compared with the analytical BER of a chirp-based communication system.
In an embodiment biosensor with communication, there is a trade-off between the efficiency in which the spectral resources are utilized and the complexity of the solution to be implemented by a nanomachine. To tackle this trade-off, different system variations can be made to optimize either the complexity of implementation on a nano-node or the bandwidth occupied by the operational system. Such possible cases for optimization are as follows:
Case 1: Nanomachine complexity minimization. In its current form, the presented arrangement is aimed at reducing the nanomachine complexity while utilizing the entire bandwidth for chirp-based communication. This allows a wideband receiver with an up-chirp and down-chirp detector to perform signal detection and communication.
Case 2: Spectral efficiency maximization. Given the performance of the antenna as a sensor discussed in Sec. IV, the frequencies of interest are f0 (no binding) and f1 (biomarker binding). To maximize the spectral efficiency, the nanomachine could transmit a narrow band signal first at f0 and then at f1, as part of an initial Request-to-Send (RTS) in the context of a medium access control protocol for nanonetworks. These two signals could be compared by the receiver and followed by a clear to send (CTS) packet selecting the resonant band of the antenna. Therefore, if Pf0>Pf1, the next packet is sent at f0. Thus, only the resonant antenna band is utilized for transmission to maximize spectral efficiency. The trade-off for such an arrangement is that it requires a 2-way handshake before every data transmission to ensure detection can be reliably made. Such 2-way communication and MAC layer processing will add additional complexity to nano-node architecture. Additionally, if the antenna performs detection between the data packet being sent, it will require initiating a new handshake and might result in the loss of the data packet.
Case 3: Balancing complexity and spectral efficiency. To balance the two previous cases, a solution that can minimize both complexity and bandwidth of operation while resisting the frequency selective channel is needed. Such a unidirectional system can be designed by sending two simultaneous chirps at center frequencies f0 and f1, each with bandwidth X<(f1 f0)/2, namely, one chirp centered at f0 (from f0 X/2 to f0+X/2 for the non-binding state and one chirp centered at f1 (from F1 X/2 to f2+X/2) for the binding state. Thus, for any given transmission simultaneous sensing and detection can be performed. The detection results from detector design in the
In the manner described above and illustrated in the drawings, an embodiment biosensor that encodes and sends communications signals directly into the sensing light is demonstrated. Through the Internet of Nano-Bio Things architecture, embodiments can bridge nanoscale networks with cloud computing through the edge. The use of a nano patch antenna as a sensor has been investigated by modeling the effects of changing patch thickness and conductivity of the top layer of the antenna on its resonant frequency. It has been demonstrated that a change of resonating frequency can be utilized for simultaneous sensing and communication by using broadband chirp signals and performing a thorough numerical analysis. Further, a detection mechanism can be used for sensing by nanomachines such as biosensors has been demonstrated. A comprehensive analysis has been performed and the communication performance benchmarked to a standard chirp signal. The feasibility of a nano-sensing and communication system that offers the ability to perform edge sensing and can reduce the need for high computational resources required by the conventional spectrometric sensors while maintaining a minimal footprint on a nanomachine node has been established.
In one alternative detection method, power spectral density in binding and non-binding states may be compared. The source light can include two narrowband frequency components corresponding, respectively, to a first resonant frequency of the plasmonic nano-antenna in a state in which the biomarker is available and a second resonant frequency of the plasmonic nano-antenna in a state in which the biomarker is not available. The two narrowband components can correspond to the peak response frequencies 2072a and 2072b, for example.
The teachings of all patents, published applications and references cited herein are incorporated by reference in their entirety.
While example embodiments have been particularly shown and described, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the embodiments encompassed by the appended claims.
This application claims priority under 35 U.S.C. § 119 or 365 to United States Provisional, Application No. 63/237,874, filed Aug. 27, 2021. The entire teachings of the above application(s) are incorporated herein by reference.
This invention was made with government support under 2039189 from the National Science Foundation. The government has certain rights in the invention.
Filing Document | Filing Date | Country | Kind |
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PCT/US2022/041765 | 8/26/2022 | WO |
Number | Date | Country | |
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63237874 | Aug 2021 | US |