Imaging and Sensing

correlative image

Imaging and Sensing

Our quantum sensors must accurately attribute detected signatures to corresponding biochemical phenomena to generate high-precision data relevant to cell biology. In this thrust, we will work to develop small, organized two- and three-dimensional arrays of individually addressable quantum sensors that can produce hyper-resolved images of charge, electric fields, or chemical flux across a small (several nm3) volume. For example, we will seek to design a sensor array that can probe local variations in ion concentration immediately proximal to a cell membrane, or clock the flux of second messengers released during signaling. We will calibrate the quantum sensor arrays using well-characterized spatially correlated biological phenomena including the motion of actin filaments, or patch clamp measurements. These nanoscopic sensor arrays will create a new imaging paradigm for investigation of biological fluxes, gradients, and out-of-equilibrium processes at the nanoscale.

Approach

  • Task 1: An ordered array of quantum sensors that are individually addressable and densely sample a small volume of space would be invaluable in producing hyper-resolved images or maps that would far exceed the diffraction limit or even room temperature super-resolution. To create such an array, we will require a rigidly organized collection of qubits that are individually optically addressable. These arrays can be organized by a molecular structure, within a single crystal, or in a larger cross-braced scaffold of many solid-state quantum nanoparticles.
  • Task 2: The most promising isotopes for tagging are deuterium, carbon 13, and nitrogen 15. Imaging spectroscopies sensitive to molecular vibrations can be used to detect deuterium, but have low sensitivity for 13C or 15N.94,95 However, 13C and 15N have nuclear magnetic moments, which can be detected in conventional NMR spectrometers, raising the intriguing possibility of using high-resolution and high-sensitivity quantum-enhanced magnetometry for detection. Such a tool would enable, for instance, maps of candidate drug distribution through different tissues, and perhaps even which organelles the drug localizes to; or maps of protein synthesis upregulation in the brain in response to learning or memory formation.
  • Task 3: Correlative imaging analyzes conventional microscope images to extract functional relationships96,97 and exploits engineered relationships to develop images below the diffraction limit.98,99 We will utilize correlative imaging to connect specific biochemical events/properties to recorded quantum signals. Our strategy uses traditional advanced imaging and readout techniques to provide readouts that will be directly correlated to the readout of a quantum sensor.
  • Task 4: To achieve spatially dense measurements with high time resolution using our quantum sensors, we will need to integrate quantum sensor measurements with complementary classical sensing modalities that can provide nanoscale chemical sensing across an entire cell. We will exploit the exquisite sensitivity of enzymes to the local biochemical environment. Enzymatic molecular recorders that encode the concentrations of both biomolecular species and ions into the sequences of DNA and RNA molecules have provided a proof-of-principle that a large number of independent measurements within a living cell are possible at a spatial density exceeding what would be allowed if they required a light microscope readout. The recording molecules simply need to be recoverable after the fact so that the traces left behind by their measurement can be read out later by DNA/RNA sequencing. Moreover their precise positions in the cell, again regardless of their spatial density, can be subsequently resolved using a technology called a "DNA microscope" that we have previously published.