We integrate magnetic, optical, mechanical, and visual techniques to develop new techniques. For licensing or collaboration, please contact the PI, email, phone.

  1. Scanning magnetic detection
  2. Description: Magnetic detection typically does not provide both signal amplitude and sample location. This is because a single-point measurement is insufficient to provide a unique solution for both parameters. To overcome this problem and consequently quantify magnetically labelled molecules, we developed a scanning detection scheme. In this scheme, the sample is scanned across the magnetic sensor to produce a magnetic field profile, which is fitted according to dipolar magnetic field to produce both the magnetization and distance of the sample. An atomic magnetometer is used in most cases, with sensitivity of approximately 100 fT for 1 s integration time.

    Related patent:
    US patent 8570027: High resolution scanning magnetic imaging method with long detection range.

  3. Force-induced remnant magnetization spectroscopy (FIRMS)
  4. Description: A major limitation for magnetic detection is the lack of a parameter to represent molecular signature, unlike optical methods that often use frequency to yield molecule-specific information. We invented the FIRMS technique that implements mechanical force in magnetic detection to reveal precise molecular binding strength. Here, the two bonding molecules are immobilized via one of them and magnetically labeled via the other. Mechanical force is then applied to induce bond dissociation. When the mechanical force matches the binding force of the molecular interaction, the pair will dissociate and yield a decrease in the magnetic signal. This is because the dissociated magnetic labels will either be removed from the sample or undergo randomization of their magnetic dipoles. FIRMS reaches nearly 2 pN resolution that is sufficient to distinguish a single basepair for DNA duplexes.

    Related patents:
    US patent 8802057: Force-induced magnetization contrast for molecular-specific diagnostics and imaging.
    US patent 9778249: Sequence and chiral selectivity of DNA-drug interactions revealed by force spectroscopy.

  5. Super-resolution force spectroscopy (SURFS)
  6. Description: Built on the success of FIRMS, we used acoustic radiation force instead of centrifugal force to improve the force resolution to 0.4 pN. Amplified ultrasound radiation is fed to a piezo disk, which exerts acoustic radiation force on the magnetic beads used to label the molecules. A constant layer of water was designed to facilitate the coupling between the sample and piezo. This form of force generation also enabled total automation of magnetic detection and force application, an advantage over FIRMS using a centrifuge. The sub-piconewton resolution is able to distinguish a single hydrogen bond, or a fraction of a nucleotide movement during ribosome translocation.

    Related patents:
    Pending US patent application 20150117156: System and method for ultrasound identification and manipulation of molecular interactions.

  7. Exchange-induced remnant magnetization (EXIRM)
  8. Description: This technique is based on the following concept, using miRNA as an example: when the target miRNA strands are incubated with their complimentary strands that have been hybridized with mismatching RNA strands, the target miRNA strands will replace the mismatching strands. The mismatching RNA strands are magnetically labeled and differ from the target miRNA by one base. The exchange reaction will produce a decrease in the magnetic signal; the decreasing amplitude represents the quantity of the target miRNA molecules. The EXIRM technique will offer extremely low detection limit of a few thousands of molecules, an almost unlimited dynamic range, and single-base specificity. This technique is viable of being multiplexed for miRNA profiling and adopted for specific detection of proteins.

    Related patent:
    Pending US patent application 20140309134: Exchange-induced remnant magnetization for label-free detection of DNA, microRNA, and DNA/RNA-binding biomarkers.

  9. Force-induced visualization (FIV)
  10. Description: This technique simplifies EXIRM by replacing the magnetic detection with direct visual detection while maintaining the single-nucleotide resolution. Although the detection limit is not comparable to that of atomic magnetometers, FIV is precise, easy to adopt, and with almost no cost. It is based on the exchange reaction between magnetically labeled nucleic acid strands and unlabeled strands. Immobilization of the former produces a brown color in contrast to the clear color of the latter. Quantification can also be obtained by measuring the absorption using a laser pointer as the light source. FIV is effective in determining the length and motion of nucleic acids when the concentration is in the nM range, resolving the binding specificity of chemotherapeutical drugs, and estimating the concentration of biological samples involving nucleic acids.

    Related patent:
    Pending US patent application (No. 62/517,694): Force-modulated hybridization for visualizing nucleic acid length and function.

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