Magnetic sensing devices, and methods of reuse

Abstract

A method for reuse of a magnetic sensing device includes, after a detection of complexes of magnetic nanoparticles and target molecules bound to nanowell-based bioactive surfaces of the device, applying one or more debonding processes to selectively remove a biological sample, magnetic nanoparticles, and elements of one or more detection agents from the patterned surface before introduction of another biological sample. After a number of iterations of reuse and / or a verification of the operation of the device, the patterned surface is replaced.

Description

MAGNETIC SENSING DEVICES, AND METHODS OF REUSE CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 788299, filed April 14, 2025, and is related to PCT Application No.PCT / US2026 / 012376, filed January 23, 2026. the entire contents of each of which is herein incorporated by reference.BACKGROUND

[0002] In recent years, magnetic nanoparticles (MNPs) have been used for molecule detection in various fields such as biosensing, environmental monitoring, and medical diagnostics. As their name suggests, MNPs possess magnetic properties, and they can be manipulated using external magnetic fields. In addition, MNPs can be functionalized to bind or attach with target molecules (e.g., to form complexes) and allow selective detection of the target molecules.

[0003] Some existing methods for detecting molecules from tested samples face the issues of failing to detect at low analyte concentration and / or from nonspecific binding or misplacement of analytes across sensor areas apart from detection-sensitive / specific locations. To detect at single molecule level, some sensing systems have bioactive detection areas made down to several hundred nanometers.

[0004] Challenges are faced in manufacturing molecular sensor components at smaller scale while retaining reliability / consistency in detection performance. Many such devices incorporate potentially millions of magnetic sensors to ensure reliable detection.

[0005] When using such systems, such as for analyte detection, sensor components incorporating millions of bioactive surfaces and sensors can become exposed to assays and sample materials, which may interfere with subsequent and reliable reuse involving multiple distinct samples and / or assays. Replacing exposed components of such detection systems between uses can be time consuming, inefficient, and costly.

[0006] Therefore, there is a need for improvements in design and efficiency in magnetic sensor manufacture and use.SUMMARY

[0007] This summary represents non-limiting embodiments of the disclosure.

[0008] A magnetic sensing device for detecting magnetic nanoparticles and biomolecules is arranged with patterned surface of nanosized wells configured with a surface energy for binding / isolating particular types of complexes of the targeted nanoparticles / biomolecules. Proximate each of the nanowells is a magnetic sensor which is configured and arranged to detect the presence of the magnetic particles (MNPs) and of connected target biomolecules by generating and receiving responsive signals indicating a change in a magnetic field strength and / or magnetoresistance in or about the sensor.

[0009] After use of the magnetic sensor to detect target biomolecules from a sample, and rather than disposing of the sensor (or magnetic sensor array components), a process of detaching / removing molecules from on and around the patterned surface (debonding) is performed to prepare the device for additional tests of samples. The debonding process is utilized to remove detection agents (e.g., assay components) and sample material that may interfere in selectively isolating and detecting target molecules introduced from a new sample, and may include multiple debonding steps or sub-processes.

[0010] In some embodiments, detection agents include surface tethers with functional ends used to bind with a bioactive surface of the nanow ells and attach / tether additional elements of select complexes to a bioactive surface, including MNPs and target biomolecules. Elements of complexes may include detection-antibodies utilized to attach MNPs with target analytes (e.g., antigens) and capture- antibodies utilized to attach the target analytes with the surface tether, and thereby attach the complexes to the bioactive surfaces proximate respective magnetic sensors.

[0011] In some embodiments, the debonding process disrupts antigen-antibody or other interactions (e.g., PEG linker attachment) that attach MNPs and target analytes with each other and to the bioactive surface, including interactions between capture / detection- antibodies and target antigens. The debonding processes for disrupting antigen-antibody and / or other interactions may include one or more of increasing the salinity or pH of an aqueous media immersing the patterned surface. Introduction of a saline solution may increase salinity, for example, and introduction of an acid may decrease the pH of aqueous media around the patterned surface.

[0012] In some embodiments, the temperature of the patterned surface of the device is controlled (e.g., heated / cooled) to a achieve a predetermined temperature level inorder to interrupt particular interactions. For example, the temperature of an aqueous media may be controlled when introduced to the device and its patterned surface.

[0013] The salinity, acidity, and / or temperature of a debonding solution may be selected to achieve desired disruption of targeted antigen-antibody interactions without interfering with other chemical interactions intended to be maintained for a subsequent sample testing (e.g., bonding between surface tether and bioactive surface). For example, while these applications may interfere with or block captureantibody interactions with antigens, a surface tether bonding with a bioactive surface will not be significantly impacted.

[0014] In some embodiments, a cleansing process is applied to the patterned surface to remove materials that are not otherwise elements of complexes and / or may not be covalently bonded to surfaces of the device. In some embodiments, detection agents may include nonfouling solutions that prevent non-selective attachment of materials during the detection process. Certain nonfouling agents (e.g., bovine serum albumim (BSA)) may also interfere with debonding processes described herein and are subsequently removed before and / or during a debonding process. For the removal of nonfouling and other materials, debonding agents may include cleansers applied to the patterned surface during or prior to application of other debonding processes (e.g., pH / acid / temperature). In some embodiments, cleansers include a phosphate-buffered saline (e.g., sodium dodecyl sulfate (SDS)) and / or surfactants such as Polysorbate 20.

[0015] In some embodiments, the patterned surface of the device is cleansed with stronger agents to remove substantially all materials / molecules introduced during a detection process. Removal of particular surface tethers bonded with a bioactive surface may be desired, for example. In some embodiments, debonding / removal / cleansing processes include applying one or more of potassium hydroxide (KOH), sodium hydroxide (NaOH), concentrated hydrochloric acid (HC1), SC-1 solution (water, ammonia water and hydrogen peroxide mixture, used the standard RCA wafer cleaning process), or hydrofluoric acid (HF). In some embodiments, a debonding / removal / cleansing processes include one or more of applying electrochemical desorption or O2 plasma to the patterned surface.

[0016] After one or more debonding / removal / cleansing processes are applied, a sensor device is ready to be reused to test another sample. The reintroduction of thesame or other assay components (e.g., removed during the debonding process) may occur in coordination with introduction of a new sample under test.

[0017] In some embodiments, debonding and reuse of sensor devices is limited to predetermined numbers of iterations, as an eventual buildup of material or degradation of the sensor’s surfaces may impact target molecule detection reliability or quality. Limiting of such reuse may occur with the assistance of software configured to track the (re)use of particular sensor chips / components and the amount or types of debonding agents and / or cleansers the component(s) are be exposed to. In some embodiments, a component of a sensing device including the patterned surface (e.g., removable chip / cartridge) is replaced with anew component.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Objects, features, and advantages of the disclosure will be readily apparent from the following description of certain embodiments taken in conjunction with the accompanying drawings in which:

[0019] FIG. 1A is an illustrative cross-sectional view of magnetic sensing device with a target analyte and MNP captured in a nanowell proximite to a magnetic sensor according to some embodiments.

[0020] FIG. IB is an illustrative cross-sectional view of the magnetic sensing device of FIG. 1 A after debonding of a target analyte and MNP according to some embodiments.

[0021] FIG. 2 is a flow diagram of a method for reusing magnetic sensor array components for sensing biomolecules according to some embodiments.

[0022] FIG. 3 is a flow diagram of a method for reusing magnetic sensor array components for sensing biomolecules with immunoassays according to some embodiments.

[0023] FIG. 4 is an illustrative perspective view of a magnetic sensing device with a microfl uidic chamber and replaceable wafer design according to some embodiments.

[0024] It is contemplated that elements disclosed in one embodiment may be beneficially utilized in other embodiments without specific recitation. Moreover, the description of an element in the context of one drawing is applicable to other drawings illustrating that element.DETAILED DESCRIPTIONMethods and systems include magnetic sensing devices adapted for reuse to separately detect target molecules in multiple different samples (e.g., biological samples). The devices include patterned surfaces with bioactive areas (e.g., nanowells) configured to selectively isolate complexes of target molecules and magnetic nanoparticles (MNPs) detectable with magnetic sensors of the devices. Debonding processes are utilized to clear the patterned surfaces of some or all parts of the complexes between testing of separate samples.

[0025] FIG. 1 A is an illustrative cross-sectional view of magnetic sensing device 100 with a target analyte 170 and MNP 140 captured in a nano well 150 proximite to a magnetic sensor 130 according to some embodiments.

[0026] A bioactive layer 110 is configured to bind with a functional end of tether 160. Tether 160 has another functional end configured to tether with complexes 115 nanoparticles 140 and target analytes 170. The bioactive layer 110 can have a surface energy with an affinity for binding with tether 160. Bioactive layer 110 may include silicone dioxide (S1O2). for example, and tethers 160 may include a functional end of silane for binding with the bioactive layer 110.

[0027] Target complexes 115 are selectively formed with tethers 160, capture antibodies 175 adapted to bind with target analytes 170, and detection antibodies adapted to be linked with MNPs 140 and bind with analytes 170. Non-fouling agents 125 may be used to limit or prevent non-specific attachment of MNPs and other molecules from direct attachment to bioinert surface 120 (e.g., bovine serum albumin).

[0028] MNPs 140 can include magnetic materials including base metal (e.g., iron) or ferrite (e.g., iron oxide) material that can be sensed by a magnetic sensor 130. MNPs 140 can include other materials (e.g., a shell / coating) for reacting / attaching with a linker 135 that further connects with detection antibodies 145.

[0029] Layer 120 is selected / configured to be bioinert (and / or chemically inert) to the particular type of nanoparticle 140 and other elements of complexes 115 other than tether 160. Bioninert layer 120 is patterned to form nanowells 150 that expose the surface of the bioactive layer 110.

[0030] For example, a bioactive layer 110 including SiCL may be paired with a second layer 120 including a diamond like carbon (DLC). In some embodiments, tethers 160 include a functional end of silane for binding with the S1O2 surface and MNPs 140 that include iron or iron oxide cores configured to be substantially inert toDLC. In some embodiments, complexes include biotin-streptavin and / or oligonucleotide base pairings between linkers / tethers and MNPs. The surfaces of layers 110 and 120 may be further processed (e.g., with non-fouling agents 125) to reduce reactivity with target MNPs 140, tethers 160, and other materials used with a linking / binding / detection process .

[0031] A magnetic sensor 130 is arranged from beneath the exposed surface of bioactive layer 110 so as to detect the presence of an MNP 140 tethered with a complex 115. In some embodiments, sensor 130 is a magnetic tunneling junction (MTJ) sensor that senses changes to a magnetic field and / or magnetoresistance when MNP 140 is sufficiently proximate.

[0032] FIG. IB is an illustrative cross-sectional view of the magnetic sensing device of FIG. 1 A after debonding of a target analyte and MNP according to some embodiments. Prior to introduction and testing of anew sample, a debonding process is utilized to remove elements of complexes 115, including analytes 170 and other artifacts of a previously tested sample. The process may include an agent to disrupt the antigen-antibody interaction between analytes 170 and capture antibodies 175. In some embodiments, the process includes increasing the salinity and / or acidity of the media over the surfaces of layers 120 and 110, after which the surfaces are rinsed of the detached materials. Tethers 160 bound to bioactive layer 110 may be left intact and attached, including to capture antibodies 175.

[0033] FIG. 2 is a flow diagram of a method for reusing magnetic sensor array components for sensing biomolecules according to some embodiments. At block 210, a magnetic sensing device is provided, the device including a patterned surface with bioactive areas proximate magnetic sensors (e.g., device 100 of FIGs. 1A and IB). The device may be pre-configured with tethers (e.g., tethers 160) bound to the bioactive surface areas, such as bound with capture antibodies (e.g., capture antibodies 175) for capturing target analytes (e.g., target analytes 170).

[0034] At block 220. assays including reagents and MNPs are introduced to the patterned surfaces of the device and will assist in selectively attaching MNPs and target molecules / analytes to bioactive surface areas proximate to magnetic sensors (e.g., sensors 130). Samples that may include target molecules / analytes are introduced to the patterned surfaces before, during, and / or after introduction of assay elements. For example, after introduction of samples and assay elements for formingcomplexes (e.g., complexes 100), the surfaces may be washed to remove unbound materials from the surfaces (e.g.. non-target materials of samples).

[0035] At block 230, measurements from magnetic sensors are obtained for detecting the presence of target molecules / analytes. When target complexes of MNPs and target molecules form on a bioactive surface and proximate magnetic sensor (e.g., sensor 130), a change in magnetic field and / or magnetoresistance is analyzed and represented in signals received through the sensors.

[0036] The device is configured to be reused and test multiple samples separately utilizing a debonding / removal process in between tests such as further described herein.

[0037] At block 240. after processing of signals from magnetic sensors for the detection of target molecules, a determination is made of the device’s capability for further reuse / testing. In some embodiments, the determination is made based on a threshold number of testing I debonding / cleansing processes the device has been subject to and which may influence the integrity of the device surfaces and ability of the device to repeat accurate and consistent testing.

[0038] Each time a device is used in testing, information about the testing may be maintained in a computer database, for example, including the processes and agents used in a debonding I removal process between tests. In some embodiments, a relative impact on a device's capability to perform testing is maintained (e.g., an estimate of the integrity of device surfaces). In some embodiments, after a threshold number of reuses or level of reuse impact is exceeded, a warning or report may be generated indicating that the device should not be used for additional testing. The device may be discarded at block 260 in response to a determination that the device is not adequately capable of performing additional tests.

[0039] At block 250, after determining that a device is capable of reuse and further testing, the device is prepared for processing a new sample separately. Removal of remnants of the past sample is performed, including removal of target molecules. The removal or debonding process may include selective removal / debonding of detection agents used for isolating target molecules including, for example, tethers bound to bioactive surfaces (e.g., tethers 160) and / or attached molecules (e.g., of complexes 115).

[0040] In some embodiments, the removal / debonding process includes introducing debonding agents for breaking bonds between detection agents (e.g., captureantibodies) and target molecules / analytes, and results in the detachment of the target molecules from the testing surfaces of the device. For example, debonding may include increasing the salinity, temperature, and / or acidity of the media around the device surfaces. In coordination with debonding, cleansing agents may be applied to clear the surfaces and (and areas around the surfaces) of detached molecules.

[0041] In some embodiments, substantially all or all of the materials (e.g., including tethers and non-fouling agents) attached or bonded with the surfaces of the device during testing are removed. Agents for removal, debonding, and cleansing may include, for example, potassium hydroxide, sodium hydroxide, hydrochloric acid, ammonia, hydrogen peroxide, electrochemical desorption, O2 plasma, and / or hydrofluoric acid.

[0042] In some embodiments, cleansing agents that may be used to remove unbound materials (e.g. BSA) while leaving tethers bound to bioactive surfaces include, for example, Polysorbate 20 and Sodium Dodecyl Sulfate (SDS). Concentrations or types of certain acids may also be utilized for selective removal of particular materials.

[0043] After the debonding / removal / cleansing process(es) are complete, the device may be reused at block 220 for testing additional samples. The device may be identified by an identification or serial number used to store information (e.g., externally or on the device) about the device’s status for reuse.

[0044] FIG. 3 is a flow diagram of a method for reusing magnetic sensor array components for sensing biomolecules with immunoassays according to some embodiments. At block 310, complexes including target molecules are formed on bioactive areas of a device's patterned surface (e.g., complexes 100 of FIG. 1).

[0045] The complexes include tethers bound to the bioactive areas and are adapted to bind with capture antibodies (e.g., capture antibodies 175). In some embodiments, a device’s bioactive surface areas are preconfigured with the tethers attached and adapted to further attach with a variety of capture antibody types (e.g., selected for particular types of target antigens). Nonfouling agents may be introduced that help prohibit the non-specific binding of molecules to bioactive and / or non-bioactive surfaces of the device.

[0046] A sample under test (e.g., blood, saliva) is introduced to the bioactive surfaces of the device which, when containing target molecules (e.g., antigen), selectively and specifically permit the formation of the complexes by completing a connectionbetween a capture antibody and detection antibody along with an attached MNP (e.g., as illustrated in FIG. 1A).

[0047] At block 320, magnetic sensor elements (e.g., magnetic tunnel junctions (MTJs)) of the device are utilized to detect the presence of MNPs (e.g., as part of complexes selectively bound to bioactive surface areas) within the proximity of the magnetic sensor elements. Signals received from the sensing elements are used to identify the presence (or lack thereof) of target molecules (e.g., analytes) that form the complexes.

[0048] After analysis of a sample within the device is completed, a verification process at block 330 determines whether the device is qualified or capable of performing additional testing with separate samples. As further described herein, qualification may be based on a monitored number of prior tests / reuses and / or debonding / removal processes that have occurred (e.g., not to exceed a particular threshold).

[0049] In some embodiments, a verification process includes performing a diagnostic test with the device. The diagnostic test may include testing of a control sample, for example, and determining if the sensors are providing results consistent with the control. Verification may be based on either or both of exceeding a threshold number of (re)uses and diagnostic testing.

[0050] At blocks 340 and 350. surfaces of the device are processed with agents for debonding / cleansing / and removal of materials / molecules that may interfere with further testing / reuse involving separate samples. In some embodiments, the processes are conducted to retain the presence of tethers bound to bioactive surfaces (e.g., tethers 160 of FIG. 1) while debonding attached target molecules (e.g., analytes 170 from capture antibodies 175) and other elements of complexes.

[0051] Debonding of target molecules (e.g., antigens) may include introduction of agents and / or processes that modulate the salinity, acidity, and / or temperature around surfaces of the device to levels that are known to interrupt an antibody I antigen interaction.

[0052] For example, a temperature of about 70 degrees Celsius is utilized to disrupt the antibody / antigen interaction of many tested target molecules. Temperature may be increased by the introduction of solutions at predetermined temperatures and / or placement of device components (e.g.. a replaceable cartridge containing the active surfaces) in a thermocyler or oven. Utilization of a PEG tether attached with afunctional end of silane to a bioactive surface of SiCh will not generally be disrupted by a temperature of about 70 or by increases in salinity or moderate acidity (e.g., having a pH of about 4 or greater).

[0053] In some embodiments, nonfouling agents and / or other materials present on the device surfaces (e.g., BSA) from a prior test are first cleansed at block 340 ensure removal of undesired materials (e.g., sample materials). Cleansing agents may include detergents like tween 20 (polysorbate 20) and SDS (sodium dodecyl sulfate), for example.

[0054] At block 360, a process for separately testing a new sample includes introducing detection agents for forming complexes adapted for the testing and detection of newly introduced target molecules. Nonfouling agents (e.g., if previously removed) may be introduced in order to prevent non-specific binding of non-targeted molecules to the device’s surfaces.

[0055] With tethers and capture antibodies intact (e.g., as illustrated in FIG. IB), MNPs and detection antibodies (including linkers for linking them together) are introduced to the areas around the device’s active surfaces, along with sample materials under test. Target molecules within the samples will cause complexes to form with MNPs, and detection utilizing magnetic sensors commences again at block 320.

[0056] If verification of reuse / retesting with the device cannot be made at block 330, the device is discarded at block 370 and / or a communication generated indicating a lack of verification.

[0057] FIG. 4 is an illustrative perspective view of a magnetic sensing device with a microfluidic chamber and replaceable wafer design according to some embodiments. A MNP sensing device 400 includes a microfluidic chamber 410 configured to flow and introduce test materials (e.g., samples, MNPs, reagents) over a magnetic sensor array 440 including surfaces / layers and sensors such as further described herein. An inflow 420 receives the test materials, which are further directed toward and over the magnetic sensor array 440, where detection of MNPs and target molecules occurs. Magnetic sensor array 440 can include a plurality (e.g., grid) of nanowells (e.g., nanowells 150 of FIG. 1).

[0058] Magnetic sensing device 400 is configured with electronics for providing power to magnetic sensor array 440. processing / propagating magnetic signals and control signals, and / or facilitating suction / pressure applied to materials with device400. Signals include those received in response to changes in magnetic fields and / or magnetoresistance in or around the sensors and indicative of the presence of MNPs, and may subsequently be directed to a computing device for further processing and storage of data.

[0059] Materials that may be passed through the device include solutions of MNPs, linkers, antibodies, surfactants, tethers, samples, debonding agents, and cleansers such as further described herein. After materials are introduced to the device through inflow 420 and microfluidic chamber 410, they may pass out of or be removed from chamber 410 via outflow 430. Flow may be assisted with pumping, suction, and / or passive force mechanisms.

[0060] Magnetic sensor array 440 and / or surfaces under which the array is integrated may be incorporated into a replaceable component 445 (e.g., cartridge), that can be inserted, removed, and replaced such as when reuse of the array and / or its surfaces cannot be verified based on the history of past uses, debonding, and / or cleaning. An identification (e.g.. programmed, RFID, barcode serial number) may be associated / integrated with device 400 and / or replaceable element 445, and used for tracking reuse as further described herein.

[0061] A computer system 450 including one or more processors is programmed and configured to assist in operation of device 400. For example, computer system 450 may be utilized to receive signals from magnetic sensor array 440 and analyze them to determine whether target molecules are present in a sample. Data and analysis obtained in connection with device 400 may be transmitted through a computer network 455 and stored in a computer database 460 or other suitable storage means.

[0062] Computer system 450 may be programmed and configured to automate introduction and removal of assay components, samples, and debonding, removal, and / or cleansing agents, powering sensors, and transmitting signals there between. For example, a pumping and / or suction mechanism may be actuated through signals from system 450 such as through a computer interface and prompting from a computer user.

[0063] Computer system 450 may be further utilized to track what debonding / removal / cleansing processes have been applied to the surfaces (e.g., of replaceable element 445) of device 400. A verification of the device’s (or element's) status for continued reuse (e.g., block 240 of FIG. 2. block 330 of FIG. 3) may be determined based on tracking and analysis by system 450.

[0064] Computer systems (e.g., computer system 450 of FIG. 4) may be utilized for assisting in performing the methods described herein, such as for controlling and powering the described magnetic sensing devices, receiving, transmitting, and processing data from the magnetic sensing devices, controlling inflow and / or outflow of samples and detection agents to and from the devices, and controlling the manufacturing processes. The computer systems may utilize any suitable number of subsystems.

[0065] In some embodiments, a computer system includes a single computer apparatus, where the subsystems can be the components of the computer apparatus. In other embodiments, a computer system can include multiple computer apparatuses, each being a subsystem, with internal components. A computer system can include desktop and laptop computers, tablets, mobile phones and other mobile devices. In some embodiments, a cloud infrastructure (e.g., Amazon Web Services), a graphical processing unit (GPU), etc., can be used to implement the disclosed techniques.

[0066] The subsystems may be interconnected via a system bus. Additional subsystems such as a printer, keyboard, storage device(s), monitor, which is coupled to a display adapter, and others (not shown). Peripherals and input / output (I / O) devices, which couple to I / O controller, can be connected to the computer system by any number of means known in the art such as input / output (I / O) port (e.g., USB, FireWire®). For example, I / O port or external interface (e.g. Ethernet, Wi-Fi, etc.) can be used to connect the computer system to a wide area network such as the Internet, a mouse input device, or a scanner. The interconnection via a system bus allows a central processor to communicate with each subsystem and to control the execution of a plurality of instructions from a system memory or other storage device(s) (e.g., a fixed disk, such as a hard drive, or optical disk), as well as the exchange of information between subsystems. The system memory and / or the storage device(s) may embody a computer readable medium. Another subsystem is a data collection device, such as a camera, microphone, accelerometer, and the like. Any of the data mentioned herein can be output from one component to another component and can be output to the user.

[0067] A computer system (e.g., including computer 450 of FIG. 4) can include a plurality of the same components or subsystems, e.g., connected together by external interface or by an internal interface. In some embodiments, computer systems, subsystem, or apparatuses can communicate over a network (e.g., network 455). Insuch instances, one computer can be considered a client and another computer a server, where each can be part of a same computer system. A client and a server can each include multiple systems, subsystems, or components.

[0068] Aspects of embodiments can be implemented in the form of control logic using hardware (e.g. an application specific integrated circuit or field programmable gate array) and / or using computer software with a generally programmable processor in a modular or integrated manner. As used herein, a processor includes a single-core processor, multi-core processor on a same integrated chip, or multiple processing units on a single circuit board or networked. Based on the disclosure and teachings provided herein, a person of ordinary' skill in the art will know and appreciate other ways and / or methods to implement embodiments of the present invention using hardware and a combination of hardware and software.

[0069] Machine learning models utilized herein, such as for analyzing magnetic sensor data for determining the presence of MNPs and attached molecules, may include one or more of a Naive Bayes (NB) model, a logistic regression (LR) model, a random forest (RF) model, a support vector machine (SVM) model, an artificial neural network model, a multilayer perceptron (MLP) model, a convolutional neural network (CNN), a Large Language model (LLM), and / or other machine learning or deep leaning models, etc. The machine learning models can be updated / trained using a supervised learning technique, an unsupervised learning technique, etc.

[0070] Any of the software components or functions described in this application may be implemented as software code to be executed by a processor using any suitable computer language such as, for example, Java, C, C++, C#, Objective-C, Swift, or scripting language such as Perl or Python using, for example, conventional or object-oriented techniques. The software code may be stored as a series of instructions or commands on a computer readable medium for storage and / or transmission. A suitable non-transitory computer readable medium can include random access memory (RAM), a read only memory (ROM), a magnetic medium such as a harddrive or a floppy disk, or an optical medium such as a compact disk (CD) or DVD (digital versatile disk), flash memory-, and the like. The computer readable medium may be any combination of such storage or transmission devices.

[0071] Such programs and / or data may also be encoded and transmitted using carrier signals adapted for transmission via wired, optical, and / or wireless networks conforming to a variety of protocols, including the Internet. As such, a computerreadable medium may be created using a data signal encoded with such programs. Computer readable media encoded with the program code may be packaged with a compatible device or provided separately from other devices (e.g., via Internet download). Any such computer readable medium may reside on or within a single computer product (e.g. a hard drive, a CD, or an entire computer system), and may be present on or within different computer products within a system or network. A computer system may include a monitor, printer, or other suitable display for providing any of the results mentioned herein to a user.

[0072] Any of the methods described herein may be at least partially performed with a computer system including one or more processors, which can be configured to perform the steps. Thus, embodiments can be directed to computer systems configured to perform elements of the steps of any of the methods described herein, potentially with different components performing a respective steps or a respective group of steps. Steps of methods herein can be performed at a same time or in a different order. Additionally, portions of these steps may be used with portions of other steps from other methods. Also, all or portions of a step may be optional. Additionally, any of the steps of any of the methods can be performed with modules, units, circuits, or other means for performing these steps.

[0073] The specific details of particular embodiments may be combined in any suitable manner without departing from the spirit and scope of embodiments of the invention. However, other embodiments of the invention may be directed to specific embodiments relating to each individual aspect, or specific combinations of these individual aspects.

[0074] The above description of example embodiments of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form described, and many modifications and variations are possible in light of the teaching above.

[0075] A recitation of "a", "an" or "the" is intended to mean "one or more" unless specifically indicated to the contrary. The use of "of is intended to mean an “inclusive or,” and not an “exclusive or” unless specifically indicated to the contrary. Reference to a “first” component does not necessarily require that a second component be provided. Moreover reference to a “first” or a “second” component does not limit the referenced component to a particular location unless expressly stated.

[0076] All patents, patent applications, publications, and descriptions mentioned herein are incorporated by reference in their entirety for all purposes. None is admitted to be prior art.

Claims

CLAIMS1. A method for reuse of a magnetic sensing device, the method comprising: obtaining a magnetic sensing device with a patterned surface comprising nanowells configured to selectively isolate and bind particular types of complexes of target biomolecules and magnetic nanoparticles (MNPs) to bioactive surfaces of the nanowells, the bioactive surfaces proximate to respective one or more magnetic sensors;introducing one or more detection agents of MNPs and binding elements to the magnetic sensing device for forming first complexes of the particular types of complexes;introducing a first biological sample to the magnetic sensing device; receiving a signal from the one or more magnetic sensors of the sensing device, the signal representing a change in a magnetic field strength or direction proximate to the sensor;determining, based on the received signal, the presence of a first target biomolecule of the biological sample attached to or comprising the particular type of nanoparticle;applying one or more debonding processes to selectively remove the first biological sample, magnetic nanoparticles, and elements of the one or more detection agents from the patterned surface of the sensing device;introducing a second one or more detection agents of MNPs and binding elements to the magnetic sensing device for forming and binding second complexes to the bioactive surfaces of the nanowells;introducing a second biological sample to the magnetic sensing device; receiving a signal from the one or more sensors of the sensing device, the signal representing a change in a magnetic field strength or direction proximate to the sensor;determining, based on the received signal, the presence of a second target biomolecule of the second biological sample attached to or comprising the particular ty pe of nanoparticle.

2. The method of claim 1 wherein the one or more detection agents comprise a surface tether with a first functional end configured to bind with the bioactive surface and a second functional end configured to connect the particular types of complexes to the bioactive surface.

3. The method of claim 1 wherein the debonding processes comprise disrupting an antigen-antibody interaction.

4. The method of claim 3 wherein the t pes of complexes comprise a captureantibody configured to bind with a target analyte, and wherein disrupting an antigenantibody interaction comprises disrupting interactions between the capture antibody and the target analyte.

5. The method of claim 4 comprising disrupting interactions and connections between the capture antibody and a surface tether configured to bind with the bioactive surface.

6. The method of claim 1 wherein the one or more debonding processes comprise introducing a solution to the patterned surface that increases one or more of a salinity or change the pH of an aqueous media immersing the patterned surface.

7. The method of claim 1 wherein the one or more debonding processes comprise introducing a detergent that cleanses the patterned surface.

8. The method of claim 7 wherein the detergent is applied to remove non-covalently bonded materials from the patterned surface prior to performing additional debonding processes.

9. The method of claim 1 wherein the one or more debonding processes comprise heating the patterned surface to a predetermined temperature.

10. The method of claim 9 wherein the ty pes of complexes comprise a biotin-streptavin and / or oligonucleotide base pairing and the one or more debondingprocesses comprise heating the patterned surface to about 70 degrees Celsius or above.

11. The method of claim 1 wherein the debonding processes comprise disrupting a bonding between a surface tether and the bioactive surface.

12. The method of claim 1 wherein the debonding processes comprise introducing a solution to the patterned surface comprising at least one of potassium hydroxide (KOH), sodium hydroxide (NaOH), concentrated hydrochloric acid (HC1), SC-1 solution, or hydrofluoric acid (HF) to the patterned surface.

13. The method of claim 1 wherein the debonding processes comprise applying at least one of electrochemical desorption or O2 plasma to the patterned surface.

14. The method of claim 1 further comprising:determining, after a plurality of applications of the one or more debonding processes, that a replacement of the patterned surface is indicated, wherein the determining is based on at least one of exceeding a threshold number of applications of the one or more debonding processes or verifying operation of the sensing device by performing a controlled test;in response to determining that the replacement of the patterned surface is indicated, performing at least one of generating an alert of the indication or causing a removal and replacement of the patterned surface to occur.

15. A system for reuse of a magnetic sensing device, the system comprising: a magnetic sensing device comprising:a patterned surface comprising nanowells configured to selectively isolate and bind particular types of complexes of target biomolecules and magnetic nanoparticles (MNPs) to bioactive surfaces of the nanowells;one or more magnetic sensors proximate to respective bioactive surfaces of the patterned surface; anda fluid chamber and mechanism for introducing and removing a flow of detection agents, debonding agents, and cleansing agents on and around the patterned surface;one or more processors programmed and configured to:cause the introduction of one or more detection agents of MNPs and binding elements through the fluid chamber for forming first complexes of the particular types of complexes;cause the introduction of a first biological sample through the fluid chamber;receive a signal from the one or more sensors of the sensing device, the signal representing a change in a magnetic field strength or direction proximate to the sensor;determine, based on the received signal, the presence of a first target biomolecule of the biological sample attached to or comprising the particular type of nanoparticle;cause the application of one or more debonding agents to the patterned surface to selectively remove the first biological sample, magnetic nanoparticles, and elements of the one or more detection agents from the patterned surface;cause the introduction of a second one or more detection agents of MNPs and binding elements to the magnetic sensing device for forming and binding second complexes to the bioactive surfaces of the nanowells;cause the introduction of a second biological sample through the fluid chamber;receive a signal from the one or more sensors of the sensing device, the signal representing a change in a magnetic field strength or direction proximate to the sensor;determine, based on the received signal, the presence of a second target biomolecule of the second biological sample attached to or comprising the particular type of nanoparticle.

16. The system of claim 15 wherein the one or more detection agents comprise a surface tether with a first functional end configured to bind with the bioactive surface and a second functional end configured to connect the particular types of complexes to the bioactive surface.

17. The system of claim 3 wherein the types of complexes comprise a captureantibody configured to bind with a target analyte, and wherein disrupting an antigenantibody interaction comprises disrupting interactions between the capture antibody and the target analyte.

18. The system of claim 15 wherein the one or more debonding processes comprise introducing a solution to the patterned surface that increases one or more of a salinity, temperature, or pH of an aqueous media immersing the patterned surface.

19. The system of claim 15 wherein the one or more debonding agents comprises a detergent applied to remove non-covalently bonded materials from the patterned surface prior to performing additional debonding processes.

20. The system of claim 15 wherein the one or more processors are configured to:determine, after a plurality of applications of the one or more debonding processes, that a replacement of the patterned surface is indicated, wherein the determining is based on at least one of exceeding a threshold number of applications of the one or more debonding processes or verifying operation of the sensing device by performing a controlled test;in response to determining that the replacement of the patterned surface is indicated, performing at least one of generating an alert of the indication or causing a removal and replacement of the patterned surface to occur.

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