Systems for intra-operative collection and analysis of biological tissues

Abstract

To provide a surgical device for using a detection and / or an excision head connected to a suction tube for transferring any biological tissue to a container that receives a sampled tissue for real-time analysis as it moves through the suction tube.SOLUTION: A system for sampling a biological tissue from a zone of interest having received a biomarker prior to or simultaneously with surgery includes: an excision head connected to a receptacle for a tissue sample by a suction transfer tube; a detection sleeve surrounding a reference zone of the suction transfer tube, the detection sleeve comprising at least one sensor sensitive to the biomarker; and an electronic circuit delivering an electrical signal representative of the presence or absence of a marker when the tissue sample passes through the reference zone.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a surgical device for sampling any biological tissue, particularly tumors, using a detection head and / or ablation head connected to a suction tube and transferring the sampled tissue to a container receiving the sampled tissue for real-time analysis as it travels through the suction tube and / or for subsequent anatomic pathological diagnosis, including proteomic, metabolomic or genotypic studies. [Background technology]

[0002] To facilitate the localization of the tissue to be detected and analyzed, products are injected intraoperatively, either close to the area of ​​interest or intravascularly or into the lymphatic system. The three most frequently used products are dyes (injected in the operating room a few minutes before the operation), fluorescent molecules or radioactive substances (injected a few hours before or during the operation). These products may be combined.

[0003] The collected tissue is detected, counted, geolocated within the tumor area, and then stored in an identified and labeled container. The collected tissue is then analyzed in the operating room or sent to a laboratory for immediate pathological analysis or, in some cases, biochemical and genotyping testing.

[0004] These techniques can also be used to improve the accuracy of tumor diagnosis from biopsies by guiding the surgeon to areas of relevant tissue to determine the histological nature of the tumor.

[0005] These techniques make surgical procedures safer by providing surgeons with real-time information regarding the neoplastic or non-neoplastic nature of tissue samples.

[0006] In the prior art, US Pat. No. 5,999,333 relates to a biopsy system including a needle, a cutter movable relative to the needle to cut a tissue sample, a processing module, a tissue sensor, and an indicator. The tissue sensor detects the passage of the tissue sample cut by the cutter. The indicator emits an audible signal and / or a visual indicator. The indication provided by the indicator may vary based on the sensed quality of the tissue sample. The indicator may be incorporated into the biopsy instrument or may be provided as part of a remote unit. The biopsy system may also include a multi-chamber tissue sample holder. A graphical user interface may indicate which chambers of the tissue sample holder are occupied by the tissue sample.

[0007] This solution is used to verify whether the specimen has been captured.

[0008] Patent document 2 describes a tissue cutting device comprising: a central rotatable shaft having a first end and a second end; a motor operably coupled to the first end of the central rotatable shaft, the motor comprising a circuit system configured to rotate the central rotatable shaft; a movable component configured to move along at least a portion of the length of the central rotatable shaft; and an elongated, flexible cutting component having a first end and a second end, the first end of the elongated, flexible cutting component being fixed to the movable component and the second end of the elongated, flexible cutting component being fixed to the central rotatable shaft proximate to the second end of the central rotatable shaft, wherein movement of the movable component along at least a portion of the central rotatable shaft changes a shape formed by the elongated, flexible cutting component.

[0009] Also presented is US Patent No. 5,999,333, which describes a device for in vivo measurement of radiopharmaceuticals used in the diagnosis and monitoring of radiation therapy, including a measurement chamber, a radiation detector, and a cannula that may include a delivery lumen. The device is used to deliver a substance (e.g., a radioactive tracer used in a radiopharmaceutical) to a patient and to measure the level and concentration of the radioactive substance, for example, in the patient's blood, both during and after administration of the radioactive substance. In some embodiments, particles emitted by the radioactive material interact with the scintillation material, resulting in the emission of light that can be transmitted through the scintillation material and / or fiber optic material to a photodetector or processor for processing. In some embodiments, particle absorbing materials may be used to restrict the measurement to materials within the measurement chamber or other regions of interest.

[0010] Also known from the prior art are devices having a part that can be inserted into a tubular cavity, such as a miniaturized gamma ray detection probe including a part that can be inserted into a tubular cavity, comprising at least a scintillator crystal that emits light in response to ionizing radiation, preferably gamma rays, and having a volume of 30 mm 3 and the maximum cross-sectional area of ​​the probe is 10 mm 2 Patent document 4 discloses a scintillator comprising a scintillator crystal having a diameter of less than 1 mm, an optical fiber for collecting at least a portion of the light emitted by the scintillator material and transmitting it to a photoelectric converter, a photoelectric converter to which the crystal is connected via an optical fiber for collecting at least a portion of the light emitted by the scintillator crystal and transmitting it to the photoelectric converter, and optical means for viewing a cavity that can be inserted therein.

[0011] US Patent No. 5,399,633 describes a system for the analysis of biopsy samples, including a tissue sample transport mechanism that links a biopsy sample resection tool to a tissue sample holder located in a staging area of ​​an analysis unit. The tissue sample is automatically transported from the resection tool to the specimen holder, where the tissue sample is analyzed in the staging area of ​​the analysis unit. The transport mechanism may include a tube and a vacuum source. The tissue sample holder may be configured to slow down or temporarily stop the tissue sample for individual analysis, or to collect multiple tissue samples for analysis as a group. A tissue sample sorting mechanism may be used that allows for the separation of samples that can be correlated to analysis.

[0012] US Patent No. 6,399,933 describes a biopsy device including a body, a needle, a cutter, a tissue sample holder, and a gate assembly. The needle extends distally from the body. The cutter is longitudinally translatable relative to the needle and defines a cutter lumen. The tissue sample holder is coupled proximally to the body. The cutter lumen of the cutter defines at least a portion of a fluid conduit extending between the cutter and the tissue sample holder. The gate assembly is configured to selectively block movement of the tissue sample holder within the fluid conduit between the cutter and the tissue sample holder. [Prior art documents] [Patent documents]

[0013] [Patent Document 1] US Patent Application Publication No. 2012 / 2283563 [Patent Document 2] US Patent Application Publication No. 2016 / 100852 [Patent Document 3] U.S. Patent Application Publication No. 2022 / 370024 [Patent Document 4] French Patent No. 2908283 [Patent Document 5] US Patent Application Publication No. 2017 / 131311 [Patent Document 6] International Patent Application Publication No. 2018 / 102713 Summary of the Invention [Problem to be solved by the invention]

[0014] The prior art solutions are not entirely satisfactory, since the collection container contains a mixture of all tissues removed after the procedure, including healthy tissue, complicating subsequent analytical work and preventing focus on the study of pathological tissues. Furthermore, the management of radioactive waste by hospitals is strictly regulated. Indeed, certain pathologies, such as neuropathological pathologies, entail risks and require the destruction of all waste used in treatment. The waste is tracked, stored and sent to identified waste areas. Mixing marked and unmarked tissues increases the volume of special waste, which requires expensive processing for disposal.

[0015] Prior art solutions allow for real-time quantitative monitoring of the usefulness of tumor resection in tissue detected by fluorescent or radioactive markers, but do not allow correlation of count data with other information for more sensitive tracer detection by isolating the detection from the "noise" of the surgical wound.

[0016] The solutions proposed by US Pat. No. 5,999,633 or US Pat. No. 5,999,623 do not provide a solution, since they are able to detect the passage of biological material but are unable to identify whether it is cancerous tissue or not. [Means for solving the problem]

[0017] The system according to the present invention comprises: -Cutting tools(100) - a suction hose (200), preferably disposable -Set of containers(300) - a vacuum source (400) preferably connected to the hospital vacuum source via a connecting tube (325); ·Computer terminals (500) A detection sleeve (600) surrounding the suction tube (200) Includes. [Brief description of the drawings]

[0018] The invention will be better understood on reading the following description of non-limiting exemplary embodiments illustrated by the attached drawings, in which: [Figure 1] FIG. 1 shows a schematic diagram of an example of a collection system according to the present invention. [Diagram 2] FIG. 2 shows a schematic diagram of an alternative embodiment of a collection system according to the invention. [Diagram 3] FIG. 3 is a schematic diagram of a longitudinal section through a detection sleeve of a collection system according to the invention. [Figure 4] 2 is a schematic cross-sectional view of a detection sleeve of a collection system according to the present invention; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] The following description specifies some of the features of the system components. It should be noted that each component can be developed and used independently of the other components, and it should not be assumed that they are all necessarily combined with each other.

[0020] The general principle of the present invention is to provide one or more detectors on the aspiration tube (200) connecting the cutting head (100) to the container (300) for aspirated product to control one or more functions such as routing to a particular container in the set (300) or emitting an audio or optical signal in case of excessive aspiration of unmarked samples in order to characterize in real time the presence and / or nature of the sample collected through the tube during aspiration in the aspiration tube (200).

[0021] Removal tool and detector head The present invention is not limited to a particular type of cutting tool, nor to a single soft suction solution, but can be implemented with any type of cutting or soft suction tool that delivers a sample through a hose.

[0022] In one variant, the excision tool (100) consists of a head (110) (preferably disposable) formed by a tubular element through which a suction channel passes, and has several possible shapes that can be modified according to the required operating cavity, sensitivity or resolution.

[0023] The head (110) is complemented by an optical detection system (120), which is itself coupled to a computer terminal (500) driven by data control, acquisition and visualization software.

[0024] The detector head (110) measures the concentration of beta particles in the tissue near the suction mouthpiece. The signal thus received is converted into an electrical signal by an optical detection system, which is transmitted to a data acquisition module. The data is acquired, processed and displayed on the terminal (500) using computer software.

[0025] The detection and ablation head is connected to an optical fiber with a scintillator crystal at one end. The head can be inserted into the tubular cavity and moved in it to detect the presence of any gamma radiation source corresponding to potential cancer tissue that has reacted with the biomarker. The other end of the optical fiber is connected to a photoelectric converter. This photoelectric converter is the most commonly used. The optical fiber is the means of collecting and transmitting the light emitted by the crystal. The optical fiber can have an inorganic core, for example silica, or a polymer core, for example PMMA. The part of the light emitted by the crystal that is collected by the optical fiber is transmitted to the photoelectric converter, which converts it into an electrical signal, in particular an electrical pulse. Advantageously, the coupling between the optical fiber and the crystal ensures the collection of more than 5%, preferably more than 10%, of the scintillation photons emitted per event. To optimize the light collected, the optical fiber is preferably connected to the face of the crystal in the connection section, and the ratio between the surface area of ​​the crystal to which the fiber is connected and the surface area of ​​the connection section is preferably close to 1, preferably less than 5. The optical fiber is flexible, so that it can deform and adapt to the shape of the cavity into which it is inserted. Depending on the application, it is possible to use very long fibres, in particular lengths of 10 m or more. Advantageously, the core of the fibre has a diameter preferably less than 1.5 mm and the whole fibre (core + cladding) has a diameter preferably less than 3 mm. In a preferred embodiment, the entire insertable part can be bent with a radius of curvature of less than 5 cm, preferably less than 2 cm. To obtain a bending radius of less than 1.5 cm for silica core fibres, several fibres can be bonded to the same crystal. Advantageously, the insertable part has a diameter between 0.1 and 10 mm. 2 , preferably 0.2 to 5 mm 2The device has a maximum cross-sectional area (taken transversely to the longitudinal axis of the probe) of 100 nm. In one variant, the device further comprises means for quantifying the gamma rays received by the crystal by analyzing the electrical signal emitted by the photoelectric converter. This analysis can be carried out, for example, by a counting unit. The count rate then reflects the amount of gamma rays, which is directly related to the distance between the radioactive emission zone and the probe. The device can also incorporate means for calculating the distance between the probe and the detected radioactive zone. The transmitted light can be converted by a photomultiplier or a photodiode before analysis. In one embodiment, the signal from the photoelectric converter (which can be amplified if necessary) is connected to a discriminator (SCA for single channel analyzer). The signal from the discriminator is then transmitted to a count scale. In the case of using two crystals, a slow and a fast one, the signal from the photoelectric converter can be duplicated and redirected to two discriminators. One of the discriminators has a threshold set for the detection of photons emitted by the fast crystal after the absorption of a gamma ray, while the other has a threshold set for the detection of photons resulting from the detection of beta, the latter arriving diluted in time in the case of a slow scintillator. The probe according to the invention can be used to detect gamma radiation from one of the isotopes selected from 99Tc, 123I, 18F or any other isotope emitting gamma photons with an energy of more than 50 KeV. The probe according to the invention is also suitable for detecting high-energy ionizing radiation, in particular gamma radiation with an energy of more than 300 KeV. Thanks to its miniaturization, the probe according to the invention can be integrated or inserted as an accessory into various medical or diagnostic devices, such as catheters, in particular multi-channel catheters, endoscopes, telescopic instruments and devices used during surgical procedures. An endoscope conventionally comprises optical means for viewing the cavity in which it is inserted, as well as an operating channel and / or an insertion channel. The viewing means can be one or more optical fibers connected to an optoelectronic converter to obtain an image of the cavity. It is also possible to use a miniaturized camera placed at the distal end of the endoscope.The very low weight associated with the flexible shape of the optical fiber, which allows to offset the signal emitted by the scintillator crystal, means that the probe according to the invention can be used directly in standard endoscope channels. The optical observation means and the gamma radiation detection probe are placed in a guide tube, which can be compartmentalized. For example, the probe can be inserted directly into the insertion tube or into the operating channel of the endoscope, with the scintillation crystal placed at the distal end of the endoscope. The coupling of conventional optical detection techniques with the probe according to the invention is particularly advantageous. Firstly, the probe detects radioisotopes that accumulate in the tumor, enhancing the optical diagnosis of visible tumors. Furthermore, the probe according to the invention is able to detect tumors that are present deep in the tissue, and therefore cannot be observed directly. Thanks to the probe according to the invention, the detection of markings by ionizing radiation offers an important supplement to existing optical endoscope systems: the detection of small lesions, the detection of non-surface areas (1-5 cm beyond the wall, optically inaccessible) and more generally in high-contrast areas where optical analysis is difficult. This technology has great potential and a wide range of medical applications, which will continue to evolve and grow with the development of more specific probes and radiopharmaceuticals. The following examples illustrate the invention. Example 1: The detector is a rectangular crystal of LYSO:Ce3+ (Fibercryst SAS with 0.5% Ce, France), size 3*1*1 mm, polished on all sides. The optical fiber is a Thorlabs BFH37-800 fiber with a silica core of 800 mm and a numerical aperture of 0.37. The total diameter of the fiber is 1.4 mm. The length of the fiber is 1 m, polished on both ends. The crystal is bonded to one side of the fiber using a two-component epoxy adhesive (Geofix from ESCIL), which is transparent to the light emitted by the crystal. The probe head is then painted with white acrylic paint and the entire probe is painted with black acrylic paint. The output end of the probe is placed on a Hamamatsu R-647 photomultiplier. The signal from the photomultiplier is sent to a preamplifier and then to a shaping amplifier before being fed back to a pulse counter, also known as a stroke counter.The probe is then brought into contact with a radioactive source of 137Cs (gamma emitter 662 KeV) with an activity of 20 KBq. The shape of the source can be likened to a disk with a diameter of 3 mm. The probe is then retracted parallel to the disk axis in steps of 0.25 mm and the measured number of strokes is integrated over a period of 1 second.

[0026] Detection head structure The detector head (120) consists of a set of detector elements arranged in a circle around the ablation tool (110). The scintillation light from the fiber optic detector elements is directly collected and detected by a photodetection system (detector ring) consisting of silicon photomultipliers. The electrical signal generated by each SiPM is sent to an electronic acquisition system that quantifies the spectrum and count rate of beta particles detected on each fiber element.

[0027] Each detection element in the head consists of two parts: a transparent optical fiber covered by a scintillation optical fiber. The scintillation optical fiber detects radioactive emissions (gamma or beta). When a gamma or beta particle interacts with the scintillation optical fiber, a spray of scintillation photons is produced. The transparent optical fiber acts as a light guide, directing the scintillation photons away from the surgical wound.

[0028] After passing through tissue, β+ particles can be annihilated by encountering an electron. Such an annihilation generates two 511 keV γ photons that, if detected, would interfere with the direct measurement of beta particles. Due to their long average path, the detected photons may come from non-specific accumulation zones of the radiotracer located at a distance from the area of ​​interest. This background noise therefore needs to be excluded to ensure the reliability of the measurements.

[0029] To do this, the flux of photons reaching the probe is evaluated by placing detector elements that are sensitive only to gamma radiation. These detector elements are stainless steel shielded optical fibers known as "control" fibers, as opposed to unshielded fibers known as "signal" fibers (Figure 1). The signal from the control fibers is subtracted from the signal fiber, leaving only the pure beta signal.

[0030] The thickness of the scintillating portion of the "signal" fiber is optimized to achieve the best compromise in terms of maximum positron energy deposition and minimum gamma background contamination. The length of the scintillating portion of the "control" fiber is defined to reduce the statistical variability in the gamma signal measurement while minimizing the dependence of the subtraction method on the spatial variation of the background noise.

[0031] To optimize the light collection by each detector element, it was decided to add an optical coating to each fiber, covering them with a thin layer of reflective paint that would retroguide the scintillation photons emitted in the opposite direction through the transparent fiber. This coating would increase the sensitivity of the probe.

[0032] The choice of using optical fibres as the detection element of the probe is explained by the fact that both are suitable for positron detection whilst being relatively insensitive to gamma background noise.

[0033] Moreover, the variety of shapes and sizes of fibers offers flexibility when designing the geometry of the sensing head, so multiple head geometries can be proposed depending on the clinical situation, the pathology to be treated, the geometry of the surgical cavity, the resection tool selected, etc.

[0034] From a clinical point of view, optical fibers also guarantee safety for the patient and the surgeon: they are electrically inert, so they can be introduced into surgical wounds and combined with ablation tools, and finally, their compactness allows the design of miniaturized probes.

[0035] The choice of a disposable detection head simplifies post-operative tool sterilization procedures inherent in surgical practice and allows the device to maintain good sensitivity. An alternative approach is to protect the probe with a plastic cover. The addition of such a cover may reduce the performance of the detection head.

[0036] The detector head consists of a plastic optical fiber and metal parts. The metal parts could possibly be salvaged and reused for the same purpose. As the optical fiber is made of plastic, recycling possibilities could be considered.

[0037] The principle behind the use of such a resection tool is as follows: once the main visible part of the tumor has been removed and radiolabeled, the surgeon introduces a probe into the surgical wound. The surgeon first removes the visible part of the tumor using a resection tool such as an ultrasonic aspirator.

[0038] The beta radioactive tracer is then injected intravenously during surgery, 30-60 min before the tumor margins are checked, to minimize radioactive contact with operating room staff.

[0039] The detection head is then used to measure the beta particle concentration and identify tumor residues, which are then removed and aspirated.

[0040] By measuring the concentration of the radioactive tracer locally around the resection site, it becomes possible to identify any tumor residues. The sensor probe can improve the quality of surgery and increase comfort and safety by speeding up the process of searching for cancerous tissue and allowing surgeons to define tumor resection margins more precisely and in real time.

[0041] Thus, surgeons can more precisely remove tumor tissue while preserving the surrounding healthy tissue, thereby further preserving the affected organ. This less invasive, more conservative surgery allows patients to recover more quickly and maintain a better quality of life, while limiting the number of recurrences.

[0042] When using the detection head (120), the surgeon can choose between two display modes in which he receives real-time information on the location of the tumor tissue: the "counter" mode and the "imager" mode. The counter mode provides the count rate β in the set of optical fibers of which the detection head is composed. The numerical value is displayed on the screen (500) of the terminal, complemented by an audible signal with a frequency proportional to the count rate, allowing the search to be performed without taking one's eyes off the surgical wound. In the imager mode, each optical fiber is visually represented on the screen and the count rate of each fiber is designated with a color whose intensity is proportional to the value indicated. This image can be presented, for example, on a dedicated screen or directly on the microscope used by the surgeon.

[0043] On-line characterization of tissue samples passing through a reference zone The present invention differs from the prior art more specifically in that the flow through the aspiration tube (200) detects the passage of the marked sample before it is transferred to the container (300). This detection is performed by a detection sleeve (600) located in a reference zone of the aspiration tube, at a known distance from the opening to the container (300).

[0044] Tissue characterization, particularly the presence or absence of markers, is performed by a sleeve (600) containing one or more sensors adapted for a traceability mode provided in the ablation system.

[0045] This detection sleeve (600), which passes through the suction tube (200), is positioned on a reference zone of the tube (200), determined by a distance D1 from the downstream end of the tube (200) and a distance D2 from the upstream end of the tube (200). Detection can be performed by a simple light barrier or camera, or by a radiation or particle counter.

[0046] Knowing the distance D1 and the average movement speed of the sample in the suction tube makes it possible to determine the time offset of the passage through the directing valve (230) that directs the marked sample either via a branch (315) to a first container (310) or via another branch (325) to a waste container (320).

[0047] Both vessels are connected to a vacuum source (400).

[0048] Information from the sleeve (600) is used to control the valve (230) depending on whether the marker is detected.

[0049] Processing the data The sleeve (600) includes one or more sensors for detecting the passage of material or for detecting the passage of a marked sample. These sensors include a microcontroller for processing electrical signals generated by the detection. These signals are then processed to include some or all of the following functions:

[0050] Sampling and coding of signals to provide a digital data frame Timestamp of the data frame or data Filtering data to send only the data you want Adding incremental identifiers to data This data is then used by applications on the terminal (500) to provide functionality such as:

[0051] - sample routing to one of the containers (300) depending on the characteristics of the sample in question, Counting the number of marked samples Correlation with other information such as suction pressure or suction actuation or images acquired by the detection head, optionally with time shifting Activate sound or light signals.

[0052] container Alternatively, the set of containers (300) comprises a barrel made up of several containers which are moved after each sample transfer, in which case the information provided by the sleeve (600) is time-stamped and stored in a table relating to the container to which the sample characterized during its passage through the reference zone has been transferred.

[0053] In one variation, the container contains a PBS precision balance that provides real-time information regarding the mass of the collected sample.

[0054] The containers may be fitted with individual radioactivity sensors.

[0055] It may also be refrigerated to improve preservation of the harvested tissue or contain a solution to fix the harvested tissue, such as formaldehyde.

[0056] Radiation protection of a set of containers In a preferred embodiment, the containers (310, 320) are enclosed within a limited radiation-protective enclosure that advantageously features space to accommodate the patient's urinary catheter (450), thus confining all radiation sources from the patient to the radiation-protective enclosure (800).

[0057] The enclosure consists of a box whose walls contain lead sheets, typically sheets of a total thickness suitable for absorbing gamma rays of energy less than 1 MeV, designed to confine the gamma rays emitted by the sample and the patient's urine. The box has a housing for the urine bag, as well as a housing for a set of sample containers (300). Passages are provided for the passage of the urine bag conduit and the sample transfer tube (200), as well as tubes for connecting to the hospital's vacuum source. Alternatively, some passages are replaced by fluid connectors.

[0058] The radiation-safe container (310) preferentially features separate compartments, each equipped with a radiation sensor (360), for containing selected samples, rejected samples, and, if applicable, patient fluid containers. The container preferably contains selected samples, rejected tissue collections (with specific sensors), and a urine bag with sensor (350) and volume indication (the urine bag is not visible through the shielded containment and it is important for the surgeon and anesthesiologist to know the volume, color (e.g., presence of blood), concentration, etc.).

[0059] Sensors Various types of sensors can be used to characterize the sample, in particular a light barrier formed by a light source oriented transversely to the axis of the tube (200) associated with a light detector or an array of light detectors, or a camera for counting the sample and optionally imaging sections of the sample, and / or a light detector for detecting the emission of a sample marked with a phosphorescent marker, or a light detector associated with an excitation source for detecting the emission of a sample marked with a fluorescent marker, or a detector capable of counting the radioactivity of a sample labeled with a radioactive tracer.

[0060] Valve (230) may be controlled automatically based on a signal provided by sleeve (600) or manually by the surgeon. In the latter case, sleeve (600) controls the activation of an audio and / or optical signal upon detection of a marked sample, and the surgeon decides based on perception of this signal, possibly taking into account other criteria resulting from the ongoing operation, whether the sample under consideration is to be retained or rejected.

[0061] The sleeve (600) can also be connected to a mass spectrometer to characterize the presence or absence of specific proteins or exogenous tracers (glucose, dopamine, etc.) or the biochemical signature of a substance of interest.

[0062] Radiosensitive Sensors In a preferred embodiment, the sensor counts the radioactivity of the aspirated sample. For this purpose, the reference zone of the sleeve (600) comprises an inner tubular segment (610) made of a scintillator dedicated to the detection of beta particles. This inner tubular segment (610) is surrounded by a photodetector (630) wired on a printed circuit board (620) and covered with a reflective coating (615) (unless the photodetector is bonded).

[0063] This first scintillator (610) is surrounded by a second tubular segment (640) that is coaxial with the first scintillator and consists of a scintillator dedicated to gamma ray detection, covered with a reflective coating (645) and equipped with a photodetector (660) wired to a printed circuit.

[0064] The detection zone therefore consists of two concentric scintillators (610, 640). Photodetectors (of the Silicon Photomultiplier or SiPM type) are bonded to the scintillators on their outer faces and / or at their ends.

[0065] The inner beta scintillator (610) is an annular organic scintillator that detects beta particles and gamma rays. It is cylindrical on the inside and faceted on the outside for optimal contact with the silicon photomultiplier (630) that collects the signal.

[0066] The outer scintillator, called the "gamma scintillator" (640), is an inorganic scintillator, also annular, denser than the inner scintillator (610), and is superimposed on the inner scintillator (610) to detect only gamma rays. The short average path of the beta particles emitted by the sample does not allow them to reach the gamma scintillator (640).

[0067] Using the data collected by the two scintillators (610, 640) via the photodetectors (630, 660), it is possible to estimate the beta or gamma count rate of the sample, which is proportional to the amount of radioactive tracer present in the sample, using the coincidence method.

[0068] The system thus makes it possible to measure:

[0069] -Beta count rate (with gamma signal correction).

[0070] -Gamma count rate only.

[0071] If a sample passes through the detection sleeve without triggering a beta particle detection, a visual or audible safety warning is triggered. In this case, the sample has been taken from an unmarked, non-cancerous area, and the alert alerts the operator to avoid further unnecessary sampling.

[0072] Additional Sensors Figure 2 shows an example design with an additional sensor.

[0073] A light barrier (390) formed by a light source arranged to form a beam that passes laterally through the pipe (200) and a photodetector delivers a signal that changes as the sample passes through the beam field of the light barrier (390). The microcontroller (380) processes the electrical signal delivered by the light barrier (390) to deliver time-stamped information regarding the passage of the sample, or together with an identifier of the image of the sampling zone acquired with the ablation tool or an identifier that correlates with the timestamp.

[0074] The sensor (370) detects the passage of the sample from the sleeve (600) and provides a timestamp of this passage. The actuation of the sensor can trigger a safety alarm (sound or light signal) and / or control a valve (230) depending on the detection result delivered by the sleeve (600). The two detection zones (390, 600) are separated by a distance D2, and by measuring the time elapsed between them it is possible to determine the migration speed of the sample in the pipe (200) and to characterize any anomalies by comparing it to a nominal migration speed.

[0075] Another light barrier (230) also provides information regarding the time elapsed between the passage of the sample through the sleeve and the movement of the pipe section of length D1, providing an alert if deposition occurs relative to a reference time.

[0076] The system may also be equipped with additional analytical means (700) connected to the detection sleeve (600), such as a mass spectrometer, or a fluorescence counter.

[0077] Sequencing of Samples by Non-Limiting Example The surgeon controls the aspiration of the tissue: the head of the cutting tool, which comes into contact with the patient's tissue, aspirates the tissue sample, which is then drawn via a tube (200) into a set of containers (300).

[0078] The sample is drawn through the tube (200) by this suction and passes to the reference zone where a detection sleeve checks for the presence or absence of marker in the sample passing it at a given time t, allowing it to be directed to a waste container or a container for subsequent analysis.

[0079] According to certain embodiments, a pressure switch type sensor detects the closure of the hole and therefore the start of the sampling sequence, and the state of this sensor is time-stamped and recorded along with an image of the sampling zone of the surgical wound delivered by the detection head (120), also recorded in a time-stamped format.

[0080] The signal provided by the sleeve (600) is also time-stamped.

[0081] Resynchronization of the information takes into account the average time traveled by the sample in the tube (200) over the length D2 between the cutting tool and the sleeve (600) and the length D1 between the container (300) and the sleeve (600).

[0082] This information is used to provide additional information regarding the tissue sampled and collected at a given time. By providing a barrel with multiple containers, each tissue sequence removed is collected in a specific container associated with a reference time that can be used to correlate it with the images provided by the imaging device of the resection tool and the information provided by the sleeve (600).

Claims

1. 1. A system for sampling biological tissue from a target zone receiving a biomarker prior to or concurrently with surgery, comprising: The system includes a cutting head (100) connected to a container (300) for the tissue sample by a suction transfer tube (200); a sensing sleeve (600) surrounding a reference zone of said aspiration transfer tube (200), said sensing sleeve (600) including at least one sensor for sensing said biomarker; an electrical circuit that delivers an electrical signal indicative of the presence or absence of a marker when a tissue sample passes through the reference zone; 1. A system for sampling biological tissue, comprising:

2. 2. The system for sampling biological tissue according to claim 1, characterized in that, when a marker is detected, the electrical signal controls whether the tissue sample that has just passed the reference zone is transported to the container or, by default, to another container.

3. 10. A system for sampling biological tissue as claimed in claim 1, comprising a transfer suction actuator that delivers a time-stamped electrical signal, said electrical signal indicative of the presence of a marker also being time-stamped.

4. 2. A system for sampling biological tissue according to claim 1, characterized in that said sensor is formed by an annular organic scintillator (610) for detecting beta particles and gamma rays and a photodetector (630).

5. 5. The system for sampling biological tissue as described in claim 4, characterized in that the annular organic scintillator (610) detects only gamma rays and is surrounded by a similarly annular inorganic gamma scintillator (640), which is associated with a second photodetector (660).

6. 2. The system for sampling biological tissue as described in claim 1, further comprising a valve (230) that directs the sampled biological tissue to a collection container or a waste container depending on information delivered by the detection sleeve (600).

7. 2. The system for sampling biological tissue according to claim 1, characterized in that the container (300) is constituted by a barrel containing a plurality of collection units.

8. 2. The system for sampling biological tissue according to claim 1, further comprising a pressure switch for detecting activation of sampling by the cutting head (100).

9. 2. A system for sampling biological tissue according to claim 1, characterized in that it comprises an enclosure for containing said container (300) whose walls are made of lead sheets.

10. 10. The system for sampling biological tissue of claim 9, wherein the enclosure comprises a plurality of housings, each housing containing a radiation sensor.

11. 11. The system for sampling biological tissue according to claim 9 or 10, characterized in that the enclosure further comprises a housing for accommodating a urine bag.

12. 2. A system for sampling biological tissue according to claim 1, characterized in that it comprises an electronic circuit for controlling a safety alarm if a biomarker is not detected.

13. 2. The system for sampling biological tissue according to claim 1, further comprising means for analyzing said biological tissue in real time with respect to specific histological and biochemical aspects.

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