Sensor pixel and imaging device for examining a sample

Abstract

The subject matter of the invention is a sensor pixel (1) for an imaging device (2) for examining a sample (3), comprising: an emitter (4), the emitter (4) being designed to emit electromagnetic radiation in a frequency band of a range comprising high frequencies and terahertz frequencies; a resonator (6) which is connected to the emitter (4) for transmission of the emitted radiation, such that the radiation can be coupled into the resonator (6), the resonator (6) being designed to form, using the coupled-in radiation, a radiation field in an examination region (8), the examination region (8) being a volume for receiving the sample (3); and a pump unit (10) which is connected to the resonator (6) and to the emitter (4) for transmission of the radiation, the pump unit (10) being designed to pump a bound state of the radiation field in the examination region (8) by means of the emitter (4). In this way, improved imaging with high-frequency radiation and terahertz radiation is provided.

Description

[0001] Sensor pixels and imaging device for examining a sample

[0002] The invention relates to a sensor pixel for an imaging device for examining a sample, comprising an emitter configured to emit electromagnetic radiation in a frequency band encompassing high frequencies and terahertz frequencies, and a resonator connected to the emitter for transmitting the emitted radiation, so that the radiation can be coupled into the resonator. The invention also relates to the imaging device for examining the sample.

[0003] Various techniques are used to examine biological samples and cells, including optical microscopy, electron microscopy, and various spectroscopic methods. These techniques offer high resolution and detailed insights into the structure and function of cells and tissues. Optical microscopy is widely used and allows for the observation of living cells in real time. Electron microscopy offers even higher resolution but is more complex and requires intricate sample preparation. Spectroscopic methods provide detailed information about the chemical composition of samples.

[0004] One disadvantage of these techniques is that they either require invasive procedures that can damage the samples, or they are limited in terms of the depth and type of information they can provide. Optical microscopy, in particular, is limited by the wavelength of the light used and can only provide information from near-surface regions of the sample. Electron microscopy often requires fixation and coating of the samples, which precludes the study of living cells. Spectroscopic methods often require long measurement times and complex evaluation procedures.

[0005] Another disadvantage is that conventional techniques are often unable to measure the dielectric properties of samples at high resolution and in real time. These properties, however, are crucial for understanding many biological processes, as they can provide information about the composition, structure, and function of cells. The inability to capture these properties precisely and quickly significantly limits the applicability of existing methods in life science research and medical diagnostics.

[0006] High-frequency and terahertz radiation have emerged in recent years as promising technologies for the investigation of biological samples. However, examining biological samples using this radiation is time-consuming and complex. Furthermore, many existing systems are expensive and difficult to scale, limiting their large-scale application. Current imaging devices are also limited in their ability to generate detailed 3D images in real time.

[0007] Starting from this, the object of the present invention is to provide a sensor pixel and an imaging device for improved imaging with high-frequency radiation and terahertz radiation.

[0008] This problem is solved by the subject matter of the independent claims. Preferred embodiments of the invention are described in the dependent claims.

[0009] According to the invention, a sensor pixel for an imaging device for examining a sample is thus provided, comprising an emitter, wherein the emitter is configured to emit electromagnetic radiation in a frequency band encompassing high frequencies and terahertz frequencies, a resonator connected to the emitter for transmitting the emitted radiation, so that the radiation can be coupled into the resonator, wherein the resonator is configured to form a radiation field in an examination area with the coupled radiation, wherein the examination area is a volume for receiving the sample, and a pumping unit connected to the resonator and the emitter for transmitting the radiation, wherein the pumping unit is configured to pump a bound state of the radiation field in the examination area with the emitter.

[0010] The sensor pixel is designed to include an emitter. This emitter is configured to emit electromagnetic radiation within a frequency band encompassing high frequencies and terahertz frequencies. This frequency band can be understood as a normally distributed frequency range with low variance and a center frequency located in the high-frequency and terahertz range, i.e., between 1 GHz and 30 THz. Radiation in this frequency range is particularly suitable for non-invasively penetrating materials while maintaining high spatial and temporal resolution. Furthermore, the sensor pixel is designed to include a resonator connected to the emitter for the transmission of the emitted radiation, allowing the radiation to be coupled into the resonator.In this case, the resonator amplifies the coupled radiation and uses it to generate the radiation field, i.e., an electromagnetic field in the area under investigation.

[0011] According to the invention, the sensor pixel further comprises a pump unit connected to the resonator, configured to pump a bound state of the radiation field within the area under investigation. In this case, the pump unit is a device that monitors and increases or decreases the energy supply from the emitter to the resonator to generate the bound state. This suppresses a radiation mode of the radiation field, resulting in more effective confinement of the radiation field. The interaction of the emitter, pump unit, and resonator enables the confinement of the radiation field within the area under investigation. An advantage of this arrangement is the improved efficiency of the resonator and the emitter.The pump unit is preferably designed as an integrated circuit that has a feedback loop between the emitter and the resonator, so that the bound states can be generated in the resonator.

[0012] Suppression of the radiation mode in the sensor pixel is achieved through the specific design of the resonator and the use of the pump unit. This arrangement leads to a more effective limitation of the radiation field and enables continuous monitoring of the resonator's resonance conditions. This is particularly advantageous for real-time analysis and monitoring, as it allows for the rapid and precise detection of changes in the sample.

[0013] When a sample, particularly a biological sample, is introduced into the area under investigation, the radiation field undergoes a detectable change. These changes can occur, for example, due to the sample's dielectric properties or its movement. The essential aspect of the invention is therefore the provision of a sensor pixel that creates a confined state of the radiation field within the area under investigation. This confined state encloses the radiation field within the area under investigation and enables improved sensitivity of the sensor pixel itself, as even the slightest changes in the confined radiation field can be detected, and errors due to radiation field dissipation are significantly reduced. This also concentrates the intensity of the radiation field within the area under investigation, thereby increasing the sensor sensitivity.The sensor pixel according to the invention provides a precise, non-invasive method for the analysis and imaging of samples, offering high resolution and sensitivity. This non-invasive method minimizes the risk of stress or damage to the samples under investigation.

[0014] According to a preferred embodiment of the invention, the radiation emitted by the emitter is emitted in a terahertz frequency band. Terahertz radiation can be understood as electromagnetic radiation in the frequency range between approximately 0.1 and 30 THz. An advantage of terahertz radiation lies in its ability to penetrate various materials while simultaneously offering high resolution. This makes it particularly suitable for the non-invasive examination of biological samples. Damage to the sample due to radiation is excluded. An emitter could, for example, be a cross-coupled oscillator serving as the source of electromagnetic radiation in the terahertz range. Such an oscillator architecture enables the generation of radiation with high frequency and power, which increases the effectiveness of the sensor pixel.

[0015] According to a preferred embodiment of the invention, the pumping unit is designed to maintain the bound state in the area under investigation by means of active pumping. Active pumping can be understood as the continuous supply of energy from the emitter to the resonator over a period of time to maintain the bound state. This arrangement reduces radiation losses and improves the confinement of the radiation field by monitoring and maintaining the resonance conditions of the resonator in the area under investigation. When the sample is introduced into the area under investigation, lossless confinement of the electromagnetic fields is achieved, which increases sensitivity and precision. The continuous monitoring of the resonance conditions enables fast and precise detections, which is particularly advantageous for real-time analysis and monitoring.

[0016] It is possible to configure the investigation area at various distances from the resonator. However, according to a preferred embodiment of the invention, the investigation area is configured in a near-field region of the resonator at a distance of between 1 pm and 5 pm, particularly at a distance of 2 pm. The near-field region can be understood as the area in the immediate vicinity of the resonator where the radiation field is held in a bound state by the pump unit. This arrangement makes it possible to generate spatially limited, lossless electromagnetic resonances, in the sense of the enclosed radiation field, within this investigation area, which further improves accuracy and sensitivity.

[0017] According to a preferred embodiment of the invention, the sensor pixel comprises a sensor pixel area formed between the resonator and the area under investigation, wherein a side of the area under investigation facing the resonator is bounded by the sensor pixel area. A sensor pixel area can be understood as the area that separates the area under investigation from the resonator. This arrangement generates spatially limited, lossless electromagnetic resonances in the near-field region of the sensor pixel, adjacent to the sensor pixel area. The sensor pixel area itself is an active sensor pixel area, which, for example, enables dielectric measurement of samples that are in contact with the sensor pixel area. The sensor pixel area serves to receive the sample and to enclose the sensor pixel from the surrounding environment.According to a particularly preferred embodiment of the invention, the examination area is laterally limited by the area of ​​the sensor pixel area.

[0018] In principle, the sensor pixel area can be configured in various ways. However, according to a preferred embodiment of the invention, the sensor pixel area is formed with a dielectric material having a thickness of 2 pm. The thickness of the sensor pixel area thus advantageously corresponds to the distance between the area under investigation and the resonator. A dielectric can be understood as a non-conductive material that can influence the radiation field. In the near field, this enables the transmission of the radiation field through the sensor pixel area, and thus the generation of the bound state in the area under investigation, with reduced radiation losses. Furthermore, the radiation field can be concentrated directly at the sensor pixel area itself using this type of sensor pixel area.A significantly increased accuracy in detecting changes in the radiation field is achieved by contacting the sample with the sensor pixel surface.

[0019] According to a preferred embodiment of the invention, the sensor pixel area is designed to bind samples in the form of biological cells. Such a sensor pixel area is thus biofunctionalized and can be understood as a surface that has been specially treated to enable the binding of biological cells. For example, cell adhesion molecules can be applied to the sensor surface to facilitate such binding.

[0020] In principle, various resonators can be formed within the sensor pixel. However, according to a preferred embodiment of the invention, the resonator is a double-split-ring resonator. A double-split-ring resonator can be understood as a special resonator structure consisting of two concentric, split rings. This resonator utilizes a 3D topography to enable improved confinement of the radiation field within the area under investigation.

[0021] In principle, the sensor pixel can be configured in various ways. However, according to a preferred embodiment of the invention, the sensor pixel is configured with a detector. The resonator has a resonator input and a resonator output. The resonator input is connected to the emitter for transmitting the emitted radiation, the detector is connected to the resonator output for transmitting the radiation from the radiation field, and the detector is configured to detect changes in the radiation field within the area under investigation. The detector can be understood as a device that measures changes in the radiation field. The radiation from the radiation field is coupled into the detector, thereby enabling precise detection of changes in the radiation field. In principle, it is possible to detect various changes with the detector.According to a preferred embodiment of the invention, the detected change is a detuning of the resonator upon introduction of a sample into the area under investigation. A detuning of the resonator can be understood as a change in the resonator's resonance frequency caused by the presence of a sample in the area under investigation. This arrangement enables precise sample detection, as any change in the radiation field can be reliably measured. A detection principle is therefore based on a change in the local field strength of the bound state within the radiation field. As mentioned earlier, this change can be attributed, for example, to movements of the sample or its dielectric properties.

[0022] According to a preferred embodiment of the invention, the detector is connected to the emitter for transmitting the emitted radiation, and the detector is configured to detect changes in the radiation field within the area under investigation by comparing it to the emitted radiation of the emitter. This enables even more precise detection of the relationship between the emitted radiation and its changes within the radiation field. The detector can compare a target value in the form of the emitted radiation with an actual value in the form of the detected radiation in the radiation field, thereby determining the change in the radiation field or the shift in the resonance frequency.

[0023] According to a preferred embodiment of the invention, the sensor pixel is provided with a control unit and a data processing unit. The control unit is connected to the resonator and the detector for signal transmission, and the data processing unit is connected to the detector for signal transmission. The control unit is configured to detect the intensity of the radiation field in the area under investigation and, based on this detection, to manipulate the sensitivity of the detector in the area under investigation. The data processing unit is configured to convert changes in the radiation field detected by the detector when the sample is introduced into the area under investigation into permittivities. This enables precise control and adjustment of the sensitivity of the sensor pixel's detector, which increases the accuracy and efficiency of the measurements.The data processing unit is designed to convert changes in the radiation field detected by the detector when a sample is introduced into the sensor pixel's detection area into permittivities. In this case, permittivity is a relative permittivity E. r = “ This refers to the dimensionless ratio of the sample's permittivity to the permittivity E0 of the vacuum. "Manipulating" in this context means increasing or decreasing the detector's sensitivity. Sensitivity, therefore, is the accuracy with which changes in the radiation field or changes in the resonator's resonance frequency can be detected.

[0024] According to a preferred embodiment of the invention, the sensor pixel is designed as an integrated circuit. An integrated circuit can be understood as an electronic circuit integrated on a single semiconductor chip. This arrangement offers the advantage of a compact and efficient design, which increases the performance and reliability of the sensor pixel. In this context, according to a particularly preferred embodiment of the invention, the integrated circuit is deposited on a silicon chip. The silicon chip can be understood as a thin silicon wafer that serves as a substrate for integrated circuits. This arrangement offers the advantage of high integration and compatibility with existing technologies, which further increases the efficiency and performance of the sensor pixel. In principle, the sensor pixel area can have various sizes.However, according to a preferred embodiment of the invention, the sensor pixel area is rectangular and has an area of ​​0.1575 mm. 2 exhibits. In particular, an edge length of 350 pm and an edge length of 450 pm are preferred. With this sensor pixel area, a high resolution in the submillimeter range is possible.

[0025] The invention further relates to an imaging device with a plurality of sensor pixels, as described above, wherein the sensor pixels are arranged in a sensor pixel matrix such that the examination areas of the sensor pixels are laterally adjacent to one another. The sensor pixel matrix can be understood as an arrangement of sensor pixels in an ordered pattern, typically in the form of a grid. The lateral adjacency of the examination areas means that the individual examination areas are adjacent to one another without gaps, so that larger samples or a multitude of samples can be examined by forming the sensor pixel matrix. The lateral extent of the examination area of ​​the individual sensor pixel determines the resolution at which the samples can be examined. An advantage of this arrangement is the seamless coverage and the formation of an enlarged examination area.An enlarged sensor pixel area results in continuous and seamless imaging of the sample. This increases the spatial resolution and accuracy of the generated images, as there are no gaps between the areas examined by the individual sensor pixels. The continuous coverage enables more precise capture of details within the sample and improves the efficiency and accuracy of imaging and analysis.

[0026] Another advantage of this arrangement is the increased sensitivity and signal intensity. Since the examination areas are directly adjacent to each other laterally, the radiation can be used more efficiently, leading to improved detection and analysis.

[0027] This imaging device with multiple sensor pixels provides a precise, fast, and efficient method for the analysis and imaging of samples, particularly biological samples. The high resolution, seamless coverage, and improved sensitivity make the imaging device according to the invention especially suitable for detailed and accurate investigations.

[0028] According to a preferred embodiment of the invention, each sensor pixel is further provided to be connected to at least two other sensor pixels of the plurality of sensor pixels for signal transmission. This arrangement enables the sensor pixels of the sensor pixel matrix to be correlated with each other and allows image reconstruction of a sample when the sample is introduced into the examination areas of the sensor pixels of the sensor pixel matrix.

[0029] In this context, "correlated" means that each sensor pixel knows its position relative to the other sensor pixels. This is achieved by the sensor pixels communicating with each other, thus determining their relative positions. If each sensor pixel has a control unit, the radiation field can be detected using a parallel collective readout method as soon as the sample is within the investigation area or the near-field region of the sensor pixel area.

[0030] One advantage of this arrangement is the improved accuracy and precision in image reconstruction. Because each sensor pixel knows its position and can communicate with neighboring sensor pixels, a detailed and accurate imaging of the sample is possible. This leads to higher resolution and more precise analysis of the samples under investigation. Another advantage is the efficient use of computing power and storage capacity, as the data is read and processed in parallel and collectively. This reduces acquisition and processing time, enabling faster and more effective sample analysis. Furthermore, the ability for correlated signal transmission between sensor pixels results in coherent data processing, which improves the quality of the generated images.The integration of this sensor pixel matrix into the imaging device enables a precise, fast, and non-invasive method for the analysis and imaging of samples, particularly biological samples, offering high resolution and sensitivity. It is especially preferred that only sensor pixels located at the corners of the sensor pixel matrix are connected to two additional sensor pixels for signal transmission. Sensor pixels at the edge of the sensor pixel matrix, but not located at the corners, are connected to three additional sensor pixels for signal transmission. Sensor pixels in the sensor pixel matrix that are neither located at the edge nor at the corners are preferably connected to four additional sensor pixels for signal transmission.

[0031] According to a preferred embodiment of the invention, the imaging device is equipped with an imaging unit, wherein the imaging unit is connected to the sensor pixel matrix for signal transmission, and the imaging unit is configured to detect changes in the respective radiation fields in the respective examination areas of the respective sensor pixels over a predetermined period of time, and the imaging unit is further configured to generate images by means of a spectrogram analysis based on the changes in the radiation fields over the predetermined period of time. An imaging unit can be understood as a unit that detects images based on the individual changes in the radiation fields in the respective examination areas of the respective sensor pixels and reconstructs them taking into account the correlation of the sensor pixels.By recording changes in the respective radiation fields within the respective measurement areas of the respective sensor pixels over a predetermined period, a multiple of images are generated in the form of a video. The images are preferably captured at a frequency of 5 Hz.

[0032] Spectrogram analysis for image reconstruction utilizes the temporal and frequency representation of signals to obtain detailed information about the structure and properties of a sample. These signals represent changes in the radiation fields of the sensor pixels at the times captured by the imaging unit. The spectrogram thus shows how the frequency spectrum of the changes in the sensor pixel radiation fields alters over time, which is particularly useful for analyzing complex, dynamic processes within a sample. The individual image is achieved by converting time and frequency data into a visual representation that depicts the intensity of different frequencies at different times. Spectrogram analysis makes it possible to detect fine details and dynamic processes within the sample that would be difficult to capture using other methods.By correlating the sensor pixels, it is possible to read out the changes in the radiation fields in the investigation areas in parallel and collectively with the imaging unit, so that the changes in the radiation fields in the investigation areas can be detected at identical times in each of the sensor pixels of the sensor pixel matrix.

[0033] If, in addition, the distance between the sample and the resonators of the sensor pixels is changed over a predetermined period, changes in the radiation fields of the areas under investigation are obtained by the imaging device in the form of depth information, enabling the reconstruction of three-dimensional images over the predetermined period. If the sample is a moving biological sample, such as a roundworm or several roundworms, the pharyngeal pumping action of the roundworms can be reconstructed in the form of three-dimensional images using the imaging unit according to the invention. The pharyngeal pumping action in roundworms corresponds to a swallowing movement that leads to a change in the diameter of the roundworm itself along its longitudinal axis.With this change in diameter, the distance of the roundworm to the resonators of the sensor pixels in the areas under investigation where the roundworm is located changes over the predetermined period of time.

[0034] One advantage of this arrangement is its ability to generate detailed and accurate three-dimensional images of the sample. The parallel and collective data acquisition by the sensor pixel matrix ensures that changes in the radiation fields within the areas under investigation are processed quickly and efficiently, thus making efficient use of the imaging device's computing power and storage capacity.

[0035] According to a preferred embodiment of the invention, the sensor pixel matrix is ​​designed as an integrated circuit. This arrangement offers the advantage of a compact and efficient design, which increases the performance and reliability of the imaging device.

[0036] By combining spectrogram analysis with the integrated circuits in the imaging device, bandwidth is used efficiently, as changes in the radiation fields in the areas under investigation can be captured and processed in real time. This leads to faster and more accurate image reconstruction, which is particularly advantageous for real-time monitoring and analysis of biological samples. The ability to obtain a three-dimensional image based on spectrogram analysis offers improved visualization and analysis of samples, significantly expanding the diagnostic and analytical capabilities of the imaging device.

[0037] According to a preferred embodiment of the invention, the imaging device is equipped with a plurality of sensor pixel matrices, the sensor pixel matrices being arranged on the sides of a cuboid such that the sensor pixel surfaces face outwards. This makes it possible to introduce the imaging device as a closed system into fluids. For example, cell cultures in solution can be examined in this way. The cuboid-shaped imaging device is introduced into the solution. If, in addition, the sensor pixel surface is designed to bind samples in the form of biological cells, the cells in solution can adhere to the sensor pixel surface and be examined. Particularly preferred is the examination by determining the permittivity of the adhering cells, which allows conclusions to be drawn about sample contamination or unhealthy cells.By arranging the sensor pixel matrices on the faces of the cuboid, the overall sensor pixel area is increased compared to a two-dimensional arrangement, allowing more cells or samples to be acquired in a shorter time. This also eliminates blind spots on the imaging device.

[0038] The invention is described in more detail below with reference to the drawings and preferred embodiments.

[0039] The drawings show

[0040] Fig. 1 schematically shows a sensor pixel according to a preferred embodiment of the invention,

[0041] Fig. 2 schematically shows an imaging device according to a first preferred embodiment of the invention, and

[0042] Fig. 3 schematically shows an imaging device according to a second preferred embodiment of the invention.

[0043] Figure 1 shows a sensor pixel 1 for an imaging device 2 for examining a sample 3 according to a preferred embodiment of the invention. The sensor pixel has an emitter 4, which in this case is a cross-coupled oscillator. The emitter 4 emits electromagnetic radiation in a terahertz frequency band and is connected to a resonator 6 via an intermediate pump unit 10 for transmitting this terahertz radiation. The resonator 6 is a double-split-ring resonator with which a terahertz radiation field is generated in the examination area 8 of the sensor pixel 1. The examination area 8 is separated from the resonator 6 in a near-field region by a 2 pm thick dielectric sensor pixel area 12. The pump unit 10 is a feedback loop with which the energy supply from the emitter 4 to the resonator 6 is continuously monitored and increased or decreased.The power is reduced to actively pump a bound state in the terahertz radiation field. The pump unit 10 and the emitter 4 are connected to a resonator input 16 of the resonator. A detector 14 is connected to a resonator output 18 for transmitting the radiation from the radiation field. The detector 14 is connected to transmit the radiation emitted by the emitter 4, so that a change in the radiation field when the sample 3 is introduced into the investigation area 8 is detected by comparison with the emitted radiation. The radiation of the radiation field from the resonator 6 is compared with the emitted radiation from the emitter 4. The change in the radiation field corresponds in this case to a detuning of the resonator 6, i.e., a frequency change. Both the resonator 6 and the detector 14 are connected to a control unit 20.The control unit 20 is designed to detect the intensity of the radiation field in the investigation area 8 and, based on this detection, to manipulate the sensitivity of the detector 14 in the investigation area 8. A data processing unit 22 converts the frequency changes detected by the detector 14 into permittivities. Dielectric properties of the sample 3 alter a group velocity of the electromagnetic waves of the terahertz radiation field; the associated change in the radiation field frequency (fcldcs) is converted into a permittivity by the data processing unit 22. The sensor pixel 1 is designed as an integrated circuit with a rectangular sensor pixel area 12. The sensor pixel area 12 has a surface area of ​​0.1575 mm². 2The sensor has an edge length of 350 pm and an edge length of 450 pm. The examination area 8 is laterally limited by the sensor pixel area 12.

[0044] Figure 2 shows an imaging device 2 according to a first preferred embodiment of the invention. The imaging device 2 has a plurality of sensor pixels 1 arranged in a sensor pixel matrix 24. The sensor pixels 1 are interconnected for signal transmission, so that the sensor pixels of the sensor pixel matrix 24 are correlated and the position of each sensor pixel 1 relative to the other sensor pixels 1 is known. The sensor pixel matrix 24 is connected to an imaging device 26 for transmitting the changes in the radiation fields detected by the detectors 14 of the sensor pixels 1. In this specific embodiment, the sensor pixels 1 therefore do not have a data processing unit 22. The sensor pixels 1 are arranged in the sensor pixel matrix 24 such that the examination areas 8 are laterally adjacent to one another.The imaging unit 26 is designed to reconstruct the changes in the radiation fields of those sensor pixels 1, into whose examination areas 8 the sample 3 was introduced, by means of a spectrogram analysis. Changes in the radiation fields, i.e., frequency changes, are recorded over a predetermined period of time. The recorded frequency changes are read out in parallel and collectively by the imaging unit 26.

[0045] Sample 3, introduced here into examination area 8, is a live roundworm. Roundworms such as Caenorhabditis elegans have become a prominent model organism and a versatile tool for studying aging and age-related diseases such as neurodegeneration. Pharyngeal pumping behavior, a serotonin-dependent behavior, is assessed as an age-related and neuronally associated change. The pharynx is a neuromuscular organ that performs rhythmic contractions to facilitate feeding. The rate increases as the animals mature, reaching a maximum of approximately 300 pumps per minute after two days of adulthood. This rate is a good indicator of the worm's neuronal health and thus a valuable research tool. However, current methods for measuring the rate of hiccup-like movements are costly and time-consuming or require manual counting.

[0046] During pharyngeal pumping, roundworms perform rhythmic contractions of their pharynx, changing its shape while their permittivity remains unchanged. The roundworm thus locally alters its diameter. Fig. 2 shows a cross-section through the roundworm before pharyngeal pumping 28 and immediately during a contraction 30, as well as its projection into the study areas 8 of the sensor pixels 1. As soon as the roundworm performs its pharyngeal pumping, the increasing area is detected by the correlated sensor pixels 1, and the new shape can be observed in real time. With the change in diameter, the distance of the roundworm to the resonators 4 of the sensor pixels 1 in the study areas 8, where the roundworm is located, changes over the predetermined time period.The imaging unit 26 then generates three-dimensional images at a frequency of 5 Hz using spectrogram analysis, allowing precise observation of the roundworm's pharyngeal pumping. Fig. 3 shows an imaging device 2 according to a second preferred embodiment of the invention. The imaging device 2 is cuboidal and has sensor pixel matrices 24 arranged on the sides of the cuboid. Corresponding to the number of sides of the cuboid, the imaging device 2 thus has a total of six sensor pixel matrices 24. The sinusoidal lines directly adjacent to the sensor pixel surfaces 12 of the individual sensor pixels 1 symbolize the terahertz radiation field in the respective area of ​​investigation 8. In this specific embodiment, the sensor pixel surfaces 12 are biofunctionalized. They are thus designed such that biological cells 32, which in this embodiment correspond to sample 3, adhere to them. In Fig.2 Three of these imaging devices 2 were introduced into a solution containing cells 32 in order to examine the cells 32 contained in the solution.

[0047] Cellular profiling is an essential tool for understanding the physiological changes that occur in cells in response to various stimuli, including contamination with toxic metals. Toxic metals such as arsenic, cadmium, chromium, lead, and mercury can cause various health problems in humans. Therefore, it is important to correlate metal-induced toxicity with the amount of metal present in the cell. Current methods are time-consuming, expensive, and invasive.

[0048] The sensor pixels 1 of the imaging device 2 of the second embodiment correspond to the sensor pixel from Fig. 1. They make direct contact with the cells 32 via the sensor pixel surfaces 12 and detect the permittivities of the cells 32 using the respective detectors 14 and the associated data processing units 22. Toxic metals alter the naturally occurring permittivity of the cells 32 and can be detected by the imaging device 2. Similarly, the permittivity of the cells 32 changes depending on various cell properties, including cell size, shape, and morphology. Therefore, changes in cell proliferation rate, viability, and gene expression can also be detected using the imaging device 2.The sensor pixels 1 in the present imaging device 2 are uncorrelated, but are also connected to an imaging unit 26 formed in the imaging device 2 for transmitting the permittivities, so that the permittivities can be recorded over the predetermined time period. The control unit 20 can detect the intensity, i.e., in this case, the concentration of cells 32 in the solution in the investigation area 8 of the sensor pixel 1, whereupon the sensitivity of the detector 14 of the sensor pixel 1 can be manipulated accordingly, i.e., increased or decreased.

[0049] Finally, the imaging unit 26 enables the imaging device 2 to record a cell population and its changes over a predetermined period. The imaging unit 26 is configured to determine statistical parameters such as mean, variance, and autocorrelation of the cells 32 at intervals of the predetermined period or over a plurality of predetermined periods.

[0050] The invention underlying this patent application arose in the project funded by the DFG with grant number DFG PF 661 / 7-2.

[0051] Reference symbol list

[0052] 1 sensor pixel

[0053] 2 Imaging device

[0054] 3 Sample

[0055] 4 emitters

[0056] 6 Resonator

[0057] 8 Examination area

[0058] 10 pump units

[0059] 12 sensor pixel area

[0060] 14 Detector

[0061] 16 Resonator input

[0062] 18 Resonator output

[0063] 20 Control unit

[0064] 22 Data processing unit

[0065] 24 sensor pixel matrix

[0066] 26 Imaging unit

[0067] 28 Roundworm before the pharyngeal pump

[0068] 30 roundworms during pharyngeal pumping

[0069] 32 cells

Claims

Patent claims 1. Sensor pixel (1) for an imaging device (2) for examining a sample (3), comprising an emitter (4), wherein the emitter (4) is configured to emit electromagnetic radiation in a frequency band of a range encompassing high frequencies and terahertz frequencies, a resonator (6) connected to the emitter (4) for transmitting the emitted radiation, such that the radiation can be coupled into the resonator (6), wherein the resonator (6) is configured to form a radiation field in an examination area (8) with the coupled radiation, wherein the examination area (8) is a volume for receiving the sample (3), and a pumping unit (10) connected to the resonator (6) and the emitter (4) for transmitting the radiation, wherein the pumping unit (10) is configured to pump a bound state of the radiation field in the examination area (8) with the emitter (4).

2. Sensor pixel (1) according to claim 1, wherein the radiation emitted by the emitter is emitted in a frequency band of the terahertz radiation.

3. Sensor pixel (1) according to one of the preceding claims, wherein the pump unit (10) is configured to maintain the bound state in the investigation area (8) by active pumping.

4. Sensor pixel (1) according to one of the preceding claims, wherein the detection area (8) is formed in a near field region of the resonator (6) with a distance to the resonator (6) between 1 pm and 5 pm, in particular with a distance of 2 pm.

5. Sensor pixel (1) according to one of the preceding claims with a sensor pixel area formed between the resonator (6) and the area of ​​investigation (8). (12) wherein a side of the investigation area (10) facing the resonator (6) is bounded by the sensor pixel area (12).

6. Sensor pixel (1) according to claim 5, wherein the sensor pixel area (12) is formed with a dielectric having a thickness of 2 pm.

7. Sensor pixel (1) according to one of claims 5 or 6, wherein the sensor pixel area (12) of the sensor pixel (1) is configured to bind samples (3) in the form of biological cells.

8. Sensor pixel (1) according to one of the preceding claims with a detector (14), wherein the resonator (6) has a resonator input (16) and a resonator output (18), the resonator input (16) is connected to the emitter (4) for transmitting the emitted radiation, the detector (14) is connected to the resonator output (18) for transmitting the radiation of the radiation field, and the detector (14) is configured to detect a change in the radiation field in the area under investigation (8).

9. Sensor pixel (1) according to claim 8, wherein the detector (14) is connected to the emitter (4) for transmitting the emitted radiation and the detector (14) is configured to detect a change in the radiation field in the investigation area (8) by comparing it with the emitted radiation of the emitter (4).

10. Sensor pixel (1) according to claim 8 or 9 with a control unit (20) and a data processing unit (22), wherein the control unit (20) is connected to the resonator (6) and the detector (12) for signal transmission and the data processing unit (22) is connected to the detector for signal transmission, the control unit (20) is configured to detect an intensity of the radiation field in the investigation area (8) and to manipulate a sensitivity of the detector (14) in the investigation area (8) upon detection of the intensity of the radiation field. and the data processing unit (22) is designed to convert changes in the radiation field detected by the detector (14) when the sample (3) is introduced into the investigation area (8) into permittivities.

11. Sensor pixel (1) according to one of the preceding claims, wherein the sensor pixel (1) is designed as an integrated circuit.

12. Imaging device (2) with a plurality of sensor pixels (1) according to one of claims 1 to 11, wherein the sensor pixels (1) are arranged in a sensor pixel matrix (24) such that the examination areas (8) of the sensor pixels (1) are laterally adjacent to each other.

13. Imaging device (2) according to claim 12, wherein each sensor pixel (1) is connected to at least two further sensor pixels (1) of the plurality of sensor pixels (1) for signal transmission.

14. Imaging device (2) according to one of claims 12 or 13 comprising an imaging unit (26), wherein the imaging unit (26) is connected to the sensor pixel matrix (24) for signal transmission, and the imaging unit (26) is configured to detect changes in the respective radiation fields in the respective investigation areas (8) of the respective sensor pixels (1) over a predetermined period of time, and the imaging unit (2) is further configured to generate images by means of a spectrogram analysis based on the changes in the radiation fields over the predetermined period of time.

15. Imaging device (2) according to one of claims 12 to 14 with a plurality of sensor pixel matrices (24), wherein the sensor pixel matrices (24) are arranged on sides of a cuboid such that the sensor pixel areas (12) point outwards.

Images