Microfluidic biochip with enhanced sensitivity
Inventors
LEE, Eon Soo • Nunna, Bharath Babu
Assignees
New Jersey Institute of Technology
Publication Number
US-11020740-B2
Publication Date
2021-06-01
Expiration Date
2038-10-23
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Abstract
A microfluidic biochip for detecting disease antigens using gold nano interdigitated electrode circuit under a controlled self-driven flow condition is disclosed. The biochip incorporates hydrophilic microchannels for controlled self-driven flow and gold nano interdigitated electrodes for capacitive sensing with enhanced sensitivity. The biochip's microchannel has a surface treated with oxygen plasma to control microchannel surface hydrophilicity and flow rate of the biofluid sample. Carbon Nanotubes (CNTs) are utilized as an intermediate layer to enhance the binding capability to nano electrodes to enhance sensitivity. Due to the carboxylic groups of the CNTs, covalent bond binding between the antibodies and the CNTs allows the antibodies to adhere more readily on the surface of the electrodes. The quantity of antibodies attaching to the surface is increased due to the high surface to area ratio in CNTs.
Core Innovation
The invention is a microfluidic biochip that detects disease-specific antigens using a gold nano interdigitated electrode circuit under a controlled self-driven flow condition. The biochip features hydrophilic microchannels, achieved by surface treatments such as oxygen plasma, to enable precise control of the self-driven flow of biofluid samples. The nano interdigitated electrodes provide capacitive sensing with enhanced sensitivity, aided by the use of nanoparticles such as carbon nanotubes (CNTs) as an intermediate layer to increase the binding capability and density of immobilized antibodies on the electrodes.
The primary problem addressed by this invention is the difficulty in early, sensitive, and specific detection of diseases—particularly cancer—using current biochip technologies. Traditional biochips can struggle with low sensitivity and specificity, limited ability to test various sample types, difficulty in manufacturing, and lack of ease in point-of-care use. Furthermore, current biosensors often require external flow control devices, are susceptible to noise, and cannot reliably detect antigens at very low concentrations or under flow conditions.
This biochip allows a range of biofluids, including blood, urine, and saliva, to be analyzed using minimal sample volume. The capillary flow in the hydrophilic microchannels, without pumps or external devices, ensures minimal contamination and controlled reaction environments. The use of CNTs as an intermediate antibody carrier increases immobilization density due to their high surface-to-volume ratio and the presence of carboxylic groups, which permit covalent bonding to antibodies—providing strong adhesion even under shear flow rate conditions. The system detects antigen–antibody conjugations through measurement of capacitance changes in the electrode circuit, enabling detection of disease biomarkers at pico- and femto-scale concentrations.
Claims Coverage
There are two independent claims, each defining key inventive features that provide enhanced sensitivity and specific antigen detection in a microfluidic biochip using particular structural and material innovations.
Microfluidic chip with multichannel distribution, gold nano interdigitated electrodes, and nanoparticle-mediated enhanced antibody binding
The invention comprises a biochip with multiple hydrophilic microchannels originating from a single inlet, allowing controlled self-driven flow of biofluid samples such as blood, urine, or sputum by capillary action—without external pumps. Each microchannel incorporates multiple gold nano interdigitated electrodes (IDEs) positioned at different sections for capacitive biosensing. Enhanced sensitivity is achieved by chemically coated nanoparticles disposed onto a self-assembled monolayer (SAM) on the IDEs, allowing improved antibody binding compared to electrodes lacking nanoparticles. Multiple types of antibodies, such as those detecting CA-125 or HE-4 antigens, can be coated in different microchannels and sections, enabling simultaneous detection of multiple cancer biomarkers in motion within the microchannel. The system is capable of detecting ovarian cancer, including stages 1A and 1B, from very low antigen concentrations (pico- and femto-scale levels) during self-driven flow.
Microfluidic chip with nano circuit, hydrophilic microchannel, nanoparticle-SAM-antibody configuration, and controllable self-driven flow
The invention includes a nano circuit comprising at least one interdigitated nano electrode, a hydrophilic microchannel for the self-driven flow of a biofluid sample (blood, urine, or sputum), and at least one self-assembled monolayer (SAM) covering the electrode. An antibody is disposed on the electrode via deposition onto nanoparticles present on the SAM layer, enabling enhanced and more stable adhesion compared to configurations without nanoparticles. The nanoparticles can be selected from a group consisting of metallic (gold, silver) or non-metallic carbon materials (such as carbon nanotubes, graphene, or active carbon), or combinations thereof. Antigen/antibody complex formation is detected by monitoring changes in capacitance in the nano circuit as the biofluid sample flows through the microchannel by a controlled capillary effect, without external force. This configuration enables the detection of biomarkers such as CA-125 and HE-4 at very low concentrations, specifically facilitating early-stage (1A or 1B) ovarian cancer screening.
The claims focus on a multichannel, self-driven microfluidic biochip incorporating gold nano interdigitated electrodes and nanoparticle-enhanced antibody immobilization, which together enable highly sensitive, multiplexed biomarker detection from biofluids under controlled flow conditions.
Stated Advantages
Enables detection of disease-specific antigens at very low concentrations (pico- and femto-scale), enhancing sensitivity.
Allows controlled self-driven flow of biofluid without external devices, reducing contamination risk and simplifying operation.
Incorporation of nanoparticles, especially CNTs, increases antibody immobilization and stability under shear flow, improving detection sensitivity and reliability.
Can detect multiple biomarkers simultaneously in different microchannels, enhancing diagnostic capability for early-stage disease.
Reduces device size, process time, cost, and complexity compared to conventional biosensor or diagnostic platforms.
Applicable to a variety of sample types, including blood, urine, saliva, and spinal fluid, broadening usability.
Non-optical electrical sensing (capacitance measurement) decreases equipment cost and allows for miniaturization.
Capable of integrating into point-of-care, lab-on-chip, and digital devices (USB, IoT), facilitating clinical and remote diagnostics.
Documented Applications
Detection and early diagnosis of ovarian cancer, including stages 1A and 1B, by measuring CA-125 and HE-4 biomarkers.
Use as a point-of-care device for disease antigen detection in clinical and remote settings.
Lab-on-chip technology for biosensing in small sample volumes.
Point of screening device for health monitoring.
Detection of drug effectiveness via biomarker monitoring.
Detection of multiple diseases by measuring different biomarkers in the same or different channels.
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