Optical detection of a substance in fluid
Inventors
Neijzen, Jacobus Hermanus Maria • Nieuwenhuis, Jeroen Hans • Van Doorn, Arie Rombertus • Irmscher, Matthias
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Assignees
Siemens Healthineers Nederland BV
Member
Siemens HealthineersSiemens Healthineers is dedicated to pioneering breakthroughs in healthcare, providing innovative technologies and services in diagnostic and therapeutic imaging, laboratory diagnostics, and digital health solutions. Our mission is to enhance healthcare providers' value and improve patient outcomes globally. We are also committed to sustainability, aiming to minimize environmental impact while advancing healthcare.
Siemens Healthineers is dedicated to pioneering breakthroughs in healthcare, providing innovative technologies and services in diagnostic and therapeutic imaging, laboratory diagnostics, and digital health solutions. Our mission is to enhance healthcare providers' value and improve patient outcomes globally. We are also committed to sustainability, aiming to minimize environmental impact while advancing healthcare.
Publication Number
US-12339233-B2
Publication Date
2025-06-24
Expiration Date
2036-12-20
Abstract
The invention relates to a system (1) for optically detecting at least one substance in a fluid (200). The system (1) comprises particles (400, 410) arranged to be dispersed in the fluid (200), each one comprising a magnetic bead (400) and an agent (410). The agent (410) is reactive with said substance such that it gives a specific optical response upon a determined optical excitation or a chemical reaction. The system (1) further comprises a chamber (330) to contain said fluid (200) and particles (400, 410). The chamber (330) is closed at one side by a window (310) optically transparent to the wavelengths of said optical response and said optical excitation. The system (1) further comprises an optical reading system (100) adapted to detect at least a portion of said optical response. The system (1) further comprises magnetic sources (103) arranged to magnetically move the particles (400, 410) onto or close to the window (310). The optical reading system (100) is positioned to receive at least a portion of the optical response from the at least one agent (410) located onto or close to the window (310). The invention relates further to a disposable and a method.
Core Innovation
The invention relates to a system for optically detecting at least one substance in a fluid by using particles dispersed in the fluid. Each particle comprises a magnetic bead and an agent that is reactive with the targeted substance such that it produces a specific optical response upon a determined optical excitation or a chemical reaction. The system includes a chamber to contain the fluid and particles, with the chamber closed at one side by a window that is optically transparent to the wavelengths of the optical excitation and optical response. An optical reading system detects at least a portion of the optical response from the particles located onto or close to this window.
The problem addressed by the invention arises from the difficulty of detecting fluorescent or luminescent responses in opaque fluids due to absorption and scattering of emitted wavelengths within the sample. Conventional methods require processing the sample to increase transparency, which adds complexity and cost. The invention solves this by magnetically moving and retaining the particles containing the reactive agents close to the window to minimize fluid interference and background noise, thus enabling sensitive and reliable detection even in opaque fluids.
The invention further improves detection sensitivity and reduces costs by eliminating the need for sample pre-processing and surface functionalization of the detection chamber. The magnetic manipulation of particles allows capturing the substances in the bulk of the fluid during an incubation time, then bringing and retaining the magnetic bead-agent complexes close to the transparent window for optical detection. Options include using rotating magnetic fields to enhance mixing and facilitate interaction kinetics. The optical detection can be enhanced by using a Totally Internal Reflection system generating an evanescent wave at the fluid-window interface to selectively excite particles close to the window.
Claims Coverage
The patent includes one independent system claim and one independent method claim, covering features of the optical detection system and corresponding detection method. There are twelve main inventive features extracted from these independent claims focusing on the critical aspects of the system and method.
Optical detection system with magnetic bead-agent particles and selective wavelength transparent window
A system comprising particles formed by magnetic beads attached to reactive agents producing an optical response upon interaction with a target substance, a chamber with one side closed by a window that is optically transparent only to a selected portion of the spectrum including the optical response wavelength, enabling specific detection.
Dual optical detectors positioned differently relative to the window
The system includes first and second optical detectors arranged to each detect the optical response with one detector vertically aligned with the window and the other positioned differently on the same side of the window, enhancing detection capabilities.
Magnetic source operable in attraction and repulsion modes to manipulate and retain particles
A magnetic source arranged to operate in a first mode attracting magnetic bead-agent particles toward the window and a second mode repulsing them away, wherein only this magnetic source retains the particles onto or close to the sensor surface at the window-chamber interface.
Processor circuit determining substance quantity based on signals from both optical detectors
A processor circuit that determines the quantity of the target substance in the fluid based on signals from both optical detectors, which receive optical responses from the agents located upon or close to the window.
Use of optical responses including fluorescent, colorimetric, or luminescent signals upon excitation
The system's optical response produced by the agents upon interaction with the substance is selected from fluorescent, colorimetric, or luminescent signals triggered by optical excitation.
Use of Totally Internal Reflection system generating evanescent optical field at the interface
The optical source and window-chamber interface form a Totally Internal Reflection system such that incident electromagnetic waves are totally reflected, creating an evanescent optical field in the fluid near the interface that excites the particles for detection.
Optical detection of chemiluminescence without requiring an excitation source
The system can detect chemiluminescent optical responses resulting from chemical reactions via suitable detectors such as photomultiplier tubes, cameras, or FTIR detectors, without requiring external optical excitation.
Capability to perform spectral analysis on the detected electromagnetic wave
The optical detectors are arranged to perform spectral analysis of the detected optical signal to distinguish different optical responses for accurate identification and quantification.
Detection of a wide range of substances including biomolecules and small molecules
The system is configured to detect substances including proteins, enzymes, ions, small molecules with relative molecular weight smaller than 1000 Dalton, and nucleic acids, specifically listing various clinically relevant analytes.
Use of multiple agent types with different optical responses for multiplexed detection
The system can include at least one second agent reactive to a different substance producing a different second optical response upon excitation or chemical reaction, enabling multiplexed detection of multiple substances.
Sensor surface not functionalized to capture substances or analogues
The interface between the window and chamber is not functionalized with specific bindings to the target substance or analogues, relying solely on magnetic retention of the particle-agent complexes for detection.
Calculation of ratios between optical response intensities for concentration determination
A data processor calculates a ratio between the intensity of the optical response and a reference wavelength in the detected spectrum, using this ratio to determine the concentration of the substance in the fluid.
The independent claims cover a system and method incorporating magnetic bead-agent particles that produce specific optical responses, selective optical transparency at the window interface, dual optical detection, magnetic manipulation and retention of particles, and data processing for sensitive and multiplexed detection of substances in fluids without sample preprocessing or sensor surface functionalization.
Stated Advantages
Enhancement of sensitivity and reliability of existing assays and optical detection systems.
Ability to detect substances in optically opaque fluids without needing pre-processing such as filtering or chemical treatment.
Reduction of costs by avoiding complex fluid pre-processing and simplifying disposable design and manufacturing.
Improved signal-to-noise ratio by magnetically concentrating particles close to the optical window, minimizing background optical noise from the bulk fluid.
Capability to perform rapid detection due to better mixing and faster interaction kinetics via magnetic field manipulation, including rotating magnetic fields.
Compact, robust design adaptable for handheld devices by positioning magnetic sources between optical source and detectors to enhance integration.
Documented Applications
Measurement of chemical substances in biological fluids such as blood, serum, plasma, saliva, and urine.
Healthcare diagnosis via detection of substances linked to specific diseases or health problems.
Identification and quantification of small molecule substances in biological samples, including analytes such as glucose, ions, enzymes, proteins, nucleic acids, and other clinically relevant analytes listed.
Molecular diagnostics applications involving multiple-step fluid processing with potential use of separate chambers for binding steps.
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