Field portable, handheld, recirculating surface acoustic wave and method for operating the same
Inventors
Shachar, Yehoshua • Kornberg, Roger
Assignees
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Publication Number
US-11020741-B2
Publication Date
2021-06-01
Expiration Date
Abstract
A system and method for performing a portable, fast, field assay of a small sample biological analyte includes a microfluidic cartridge and a reader with which the microfluidic cartridge is selectively communicated. A closed microfluidic circuit mixes and recirculates the analyte with a buffer. A shear horizontal surface acoustic wave (SAW) detector communicates with the microfluidic circuit and has a plurality of channels including at least one functionalized sensing channel in which the mixed analyte and buffer is recirculated and sensed. Capture of the analyte is amplified by recirculation of the analyte and buffer, and detection is amplified by use of an all-purpose endospore display mass amplification.
Core Innovation
The invention is a portable field biosensing system for detecting an analyte in a small-volume biological sample using a shear horizontal surface acoustic wave (SAW) detector with an antibody-functionalized sensing lane. Sample delivery uses convection enhanced delivery (CED) that includes a distributing manifold and an active mixer coupled to the distributing manifold to uniformly distribute the mixture and increase kinetics of the analyte within a buffer solution. The system actively recirculates the biological sample through the system for a predetermined number of cycles within a predetermined time period to reduce time required for detection by increasing the probability of encounter of the analyte with the antibody in the sensing lane of the SAW detector.
The described microfluidic architecture forms a closed microfluidic circuit that repeatedly recirculates small-volume analyte with buffer using an active convection enhanced delivery mixer/pump and includes components such as a bubble trap and manifolds. The SAW detector implements functionalized sensing channels with antibody-functionalized binding interactions and non-functionalized reference channels. The recirculation and mixing are used to increase analyte-antibody encounter probability and to achieve fast assay completion within a stated time-to-result range.
Detection sensitivity is further improved by using an endospore bio-amplification approach in an ELISA-like sandwich or multi-stage sequence, where an all-purpose endospore display system can be used together with antibody- or scFv-conjugated endospore and ELISA chain recognition. Non-specific binding is reduced by detergent washing to remove non-specifically bound amplifiers and reduce false positives. The system is supported by quantitative design rationale for SAW limit of detection and modeling of convection/diffusion and binding kinetics to justify recirculation and mixing for rapid saturation.
Claims Coverage
The document includes two independent claims. Across these claims, the core inventive coverage centers on a SAW detector with an antibody-functionalized sensing lane and on convection enhanced delivery (CED) using a distributing manifold and an active mixer to uniformly distribute analyte-buffer mixture and actively recirculate the sample for a predetermined number of cycles within a predetermined time period to reduce detection time and increase analyte-antibody encounter probability. One claim further specifies the SAW interface circuit and microcontroller architecture, and another specifies the CED arrangement upstream from the SAW detector.
SAW detector with antibody-functionalized sensing lane
A shear horizontal surface acoustic wave (SAW) detector with a sensing lane functionalized with an antibody.
CED with distributing manifold and active mixer for uniform distribution and active recirculation
CED means for convection enhanced delivery of the sample to the SAW detector, including a distributing manifold and an active mixer coupled to the distributing manifold for uniformly distributing the mixture to increase kinetics of the analyte within a buffer solution and for actively recirculating the biological sample through the system for a predetermined number of cycles in a predetermined time period to reduce time required for detection by increasing the probability of encounter of the analyte with the antibody in the sensing lane of a SAW detector.
SAW interface circuit and microcontroller control architecture
A SAW interface circuit and a microcontroller, where the SAW interface circuit comprises a clock oscillator, an RF synthesizer coupled to the clock oscillator, a low pass filter and splitter having an input coupled to the RF synthesizer and an output coupled to the SAW detector, a phase/gain detector coupled to the low pass filter and the splitter and having a data input coupled to the SAW detector, an analog-to-digital converter having an input coupled to an output of the phase/gain detector and having an output coupled to the microcontroller, a pump driver, and a motor with a motor driver for mechanically loading a microfluidic cartridge.
CED upstream from SAW detector for mixture distribution and active recirculation
CED means for convection enhanced delivery of the sample to the SAW detector, including a distributing manifold and an active mixer coupled to the distributing manifold upstream from the SAW detector for uniformly distributing the mixture to increase kinetics of the analyte within a buffer solution in the SAW detector and for actively recirculating the biological sample through the SAW detector.
Across the independent claims, the patent’s claim coverage focuses on combining an antibody-functionalized shear horizontal SAW detector with a CED delivery approach using a distributing manifold and an active mixer. The CED features uniformly distribute analyte within a buffer and actively recirculate the biological sample for predetermined cycles within a predetermined time period to increase analyte-antibody encounter probability and reduce detection time, with one independent claim further specifying the SAW interface circuit and microcontroller architecture and the other specifying the CED arrangement upstream of the SAW detector.
Stated Advantages
Reduces time required for detection by increasing the probability of encounter of the analyte with the antibody in the sensing lane of a SAW detector.
Improves detection sensitivity via endospore bio-amplification while reducing false positives by reducing non-specifically bound amplifiers using detergent complex washing.
Increases kinetics of the analyte within a buffer solution in the SAW detector to support faster detection.
Documented Applications
Portable field biosensing using a disposable microfluidic cartridge and handheld reader for detecting an analyte in a small-volume biological sample.
Detection in very small analyte molecule-count samples, supported by quantitative targets such as detection when the sample contains one molecule or 10 or fewer molecules of analyte.
Virus detection where a virus analyte is specifically attached via an ELISA chain to an endospore conjugated with an Ab or scFv.
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