Enhanced sensitivity and specificity for point-of-care (POC) micro biochip
Inventors
LEE, Eon Soo • Nunna, Bharath Babu
Assignees
New Jersey Institute of Technology
Publication Number
US-11480567-B2
Publication Date
2022-10-25
Expiration Date
2038-02-15
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Abstract
An apparatus and method to detect disease-specific antigens assists in disease diagnosis. Point-of-care (POC) micro biochip incorporates at least one hydrophilic microchannel for controlled and self-driven flow of body fluid. Metallic nano-interdigitated electrodes disposed within the channels give enhanced sensitivity detection. Microchannel controls flow and amplifies a capillary effect. Electrodes are fabricated on microchannel surface to detect biomolecular interactions. When a sample flows through microchannel, disease-specific antigens from the sample form antigen-antibody complex with antibodies immobilized on electrodes. Antigen-antibody interaction is detected via an electrical change in the biochip's nano circuit. Each electrode may include a different antibody to detect different antigens. Capacitance during antigen-antibody interaction without microfluidic flow is higher than with microfluidic flow due to immobilized antibodies instability on sensing surface caused by shear stress. POC biochip provides nano level detection of many disease-specific antigens of any type based on micro volume or single drop sized sample.
Core Innovation
The invention describes a point-of-care (POC) micro biochip for detecting disease-specific antigens to assist in disease diagnosis. This biochip integrates at least one hydrophilic microchannel, fabricated from a typically hydrophobic PDMS material that is rendered hydrophilic through oxygen plasma treatment. This approach enables controlled, self-driven flow of bodily fluids such as blood, urine, saliva, or spinal fluid through the microchannels, utilizing capillary action for sample mobility without the need for external pumps.
Within the treated microchannels, metallic nano interdigitated electrodes are incorporated on the channel surface. These electrodes are functionalized with disease-specific antibodies that form antigen-antibody complexes when the target antigen is present in the sample. The resulting biomolecular interaction induces a change in the electrical properties of the nano circuit—such as capacitance—which is detected as an indicator of the presence of disease antigens. Multiple electrodes may be present, each immobilized with a different antibody to enable simultaneous detection of different antigens from a single sample drop.
The invention targets challenges in early disease detection, specificity, and sensitivity prevalent in current diagnostic methods, including limitations in conventional biochips like glass-based construction, poor sensitivity, lack of personalization, and requirement for large sample volumes or specific sample types. The improved micro biochip provides high sensitivity and selectivity for disease antigen detection, supports various body fluids, operates without external pumps, and can employ diverse channel geometries—including spiral patterns for sample separation—using flexible 3D-printed designs.
Claims Coverage
The patent contains several independent claims that highlight three main inventive features related to a POC micro biochip device and method for disease diagnostics.
Hydrophilic microchannel with controlled capillary flow via oxygen plasma treatment
The invention features at least one PDMS microchannel that is hydrophilic due to oxygen plasma treatment (duration 75–100 seconds), resulting in a contact angle between 47.07° to 62.65°, which enables controlled and improved capillary flow of bodily fluids without the need for external pumps. The hydrophobic nature of untreated PDMS is specifically not suitable for fluid analysis, and the transition to hydrophilicity is critical in achieving efficient, pump-free microfluidic operation in the device.
Metallic nano interdigitated electrodes functionalized with antibodies for enhanced sensitivity
Within the treated hydrophilic microchannels, a plurality of metallic nano interdigitated electrodes (IDEs) are disposed, each capable of being functionalized with at least one type of disease-specific antibody. The arrangement and composition (including various metals such as gold, silver, platinum, etc.) of the electrodes enable enhanced sensitivity in disease detection by promoting antigen-antibody complex formation at the sensor surface, which affects measurable electrical properties.
Detection of disease-specific antigens through electrical property changes in a nano circuit
The invention detects antigen-antibody interactions in the device by monitoring changes in electrical properties—most notably capacitance—of the incorporated nano circuit. The interaction between disease-specific antigens and immobilized antibodies alters the capacitance, and this change (measured at distinct stages: before and after complex formation) provides information on the presence and concentration of disease antigens. Specific claim coverage includes both microfluidic and non-microfluidic flow conditions and their respective differences in capacitive sensitivity.
The claims broadly cover a POC micro biochip and its use in disease diagnostics, focusing on the integration of hydrophilic, plasma-treated microchannels for controlled fluid flow, metallic antibody-functionalized nano electrodes for enhanced sensitivity, and the detection of disease antigens via changes in nano circuit electrical properties. The inventive features also include device and method embodiments, with compatibility for various bodily fluids, multiplexing via multiple electrodes, and flexible microchannel designs.
Stated Advantages
The device allows for early and enhanced sensitivity and specificity in detecting disease-specific antigens, improving chances for early diagnosis.
It simplifies the diagnostic process, enabling use in doctor offices, hospitals, laboratories, or home settings without external pumps or complex equipment.
The biochip is versatile and cost-effective, accommodating various bodily fluids including blood, urine, saliva, and spinal fluid.
Multiple antigens can be detected from a single sample on the same device, supporting simultaneous and/or personalized disease biomarker detection.
Microchannels made from polymers such as PDMS can be quickly and flexibly fabricated using 3D printing, permitting varied and optimized channel designs.
The electrical sensing methodology (e.g., capacitance) provides high sensitivity even for minimal biomolecular interactions, with low power requirements and freedom of sensor size variation.
Documented Applications
Diagnosis of complex diseases such as various cancers, including ovarian cancer, in clinical, laboratory, or home settings.
Detection and monitoring of lifestyle-related diseases such as hypertension and diabetes.
Detection and monitoring of infectious diseases including influenza.
Simultaneous detection of multiple disease antigens from a single drop of blood or other bodily fluid.
Use with different bodily fluids, such as blood (from a finger prick), urine, saliva, spinal fluid, or tissue dissolved in solution.
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