Surface acoustic wave biosensor employing an analog front end and DNA encoded libraries to improved limit of detection (LOD) with exemplary apparatus of the same
Inventors
Shachar, Yehoshua • Kornberg, Roger
Assignees
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Publication Number
US-11156542-B2
Publication Date
2021-10-26
Expiration Date
Abstract
A surface acoustic wave (SAW) performs a rapid, label-free detection of biological species. Biosensing and detection of multiple analytes multiplexed by an array of sensing lanes is configured to enable bio-amplification using engineered DNA encoded libraries as the probe through a phage display procedure to enhance specificity, capture statistics for the detection, screening and analyzing of the analyte in vitro. A biochemical formulation minimizes the limit of detection (LOD) at a threshold magnitude on the order of a femtomolar concentration. Additional enhancement of the apparatus is achieved by use of an analog front end to amplify biochemical events.
Core Innovation
The invention relates to a shear horizontal surface acoustic wave (SH SAW) biosensor with improved limit of detection (LOD), increased bandwidth, improved accuracy and resolution. It combines a crystal resonator formed from a 36° Y-cut, X-propagation LiTaO3 substrate with a microfluidic chamber integrated with interdigitated input/output frequency matched electrodes.
The crystal resonator is disposed in combination with a paired sensing lane and reference lane, and a biochemical probe is formed in a surface array on the sensing lane. The sensing lane is configured so that each biochemical probe provides detection with a LOD of at least clinical threshold values.
The biosensor includes an electronic analog front end interface (AFE) with a computational module for algorithmic data analysis and reporting, coupled with a microcontroller. The sensing lane comprises a layering of antibodies, fragmented Ab, and spacer-molecules to eliminate a false positive or a false negative.
The biochemical probe is a protein engineered probe using a phage display combinatorial antibody library. The combinatorial library provides antibodies that bind targets with affinity and specificity, where the antibodies are derived from cloned antibody genes in single-chain Fv (scFv) or Fab format for convenient manipulation.
Claims Coverage
The independent claim covers one SH SAW biosensor architecture with five inventive features: a 36° Y-cut, X-propagation LiTaO3 crystal resonator; a microfluidic chamber with paired sensing lane and reference lane and interdigitated frequency matched electrodes; an AFE plus microcontroller for algorithmic analysis and reporting; a surface-array biochemical probe configured for clinical-threshold LOD; and antibody/fragmented Ab layering with spacer-molecules, together with a phage display combinatorial antibody library for engineered binding affinity and specificity.
36° Y-cut, x-propagation litao3 crystal resonator
A crystal resonator formed from a 36° Y-cut, X-propagation LiTaO3 substrate.
Microfluidic chamber with paired sensing lane and reference lane
A microfluidic chamber integrated with interdigitated input/output frequency matched electrodes in which the crystal resonator is disposed in combination with a paired sensing lane and reference lane.
Algorithmic AFE coupled with microcontroller
An electronic analog front end interface (AFE) with a computational module for algorithmic data analysis and reporting coupled with the microcontroller.
Surface-array biochemical probe with clinical-threshold LOD
A biochemical probe formed in a surface array, with each biochemical probe having a sensing lane configured for detection with a LOD of at least clinical threshold values.
Antibody layering and spacer-molecules to eliminate false results
A sensing lane comprising a layering of antibodies, fragmented Ab, and spacer-molecules to eliminate a false positive or a false negative.
Phage display protein engineered probe
A protein engineered probe using a phage display combinatorial antibody library, with antibodies derived from cloned antibody genes in single-chain Fv (scFv) or Fab format for convenient manipulation.
The claim coverage is directed to the SH SAW crystal resonator and paired sensing/reference lane microfluidic integration with frequency matched interdigitated electrodes, the AFE computational module coupled to a microcontroller for algorithmic analysis and reporting, and the antibody-based surface array probe using fragmented Ab and spacer-molecules to eliminate false positives or false negatives.
Stated Advantages
Improved limit of detection (LOD).
Increased bandwidth.
Improved accuracy and resolution.
Detection with a LOD of at least clinical threshold values.
Elimination of a false positive or a false negative.
Documented Applications
VEGF165-based detection, with discussion of VEGFR binding and a related example of bevacizumab (Avastin) and VEGF-related detection.
Multiplexed arrays for biomarkers/pathogens as discussed in the narrative, including sensitivity/LOD discussion.
Use cases including E. coli O157:H7 and Bacillus anthracis simulant as referenced examples in the narrative.
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