Aim
We present extended depth-of-field (EDoF) miniscope, which integrates an optimized thin and lightweight binary diffractive optical element (DOE) onto the GRIN lens of a miniscope to extend the DoF by 2.8×2.8×<math><mrow><mn>2.8</mn><mo>×</mo></mrow></math> between twin foci in fixed scattering samples. Approach: We use a genetic algorithm that considers the GRIN lens' aberration and intensity loss from scattering in a Fourier optics-forward model to optimize a DOE and manufacture the DOE through single-step photolithography. We integrate the DOE into EDoF-Miniscope with a lateral accuracy of 70μm70μm<math><mrow><mn>70</mn><mtext> </mtext><mi>μ</mi><mi>m</mi></mrow></math> to produce high-contrast signals without compromising the speed, spatial resolution, size, or weight.
Conclusions
Built from off-the-shelf components and augmented by a customizable DOE, we expect that this low-cost EDoF-Miniscope may find utility in a wide range of neural recording applications.
Results
We characterize the performance of EDoF-Miniscope across 5- and 10-μm10-μm<math><mrow><mn>10</mn><mtext>-</mtext><mi>μ</mi><mi>m</mi></mrow></math> fluorescent beads embedded in scattering phantoms and demonstrate that EDoF-Miniscope facilitates deeper interrogations of neuronal populations in a 100-μm100-μm<math><mrow><mn>100</mn><mtext>-</mtext><mi>μ</mi><mi>m</mi></mrow></math>-thick mouse brain sample and vessels in a whole mouse brain sample. Conclusions: Built from off-the-shelf components and augmented by a customizable DOE, we expect that this low-cost EDoF-Miniscope may find utility in a wide range of neural recording applications.
Significance
Fluorescence head-mounted microscopes, i.e., miniscopes, have emerged as powerful tools to analyze in-vivo neural populations but exhibit a limited depth-of-field (DoF) due to the use of high numerical aperture (NA) gradient refractive index (GRIN) objective lenses. Aim: We present extended depth-of-field (EDoF) miniscope, which integrates an optimized thin and lightweight binary diffractive optical element (DOE) onto the GRIN lens of a miniscope to extend the DoF by 2.8×2.8×<math><mrow><mn>2.8</mn><mo>×</mo></mrow></math> between twin foci in fixed scattering samples. Approach: We use a genetic algorithm that considers the GRIN lens' aberration and intensity loss from scattering in a Fourier optics-forward model to optimize a DOE and manufacture the DOE through single-step photolithography. We integrate the DOE into EDoF-Miniscope with a lateral accuracy of 70μm70μm<math><mrow><mn>70</mn><mtext> </mtext><mi>μ</mi><mi>m</mi></mrow></math> to produce high-contrast signals without compromising the speed, spatial resolution, size, or weight. Results: We characterize the performance of EDoF-Miniscope across 5- and 10-μm10-μm<math><mrow><mn>10</mn><mtext>-</mtext><mi>μ</mi><mi>m</mi></mrow></math> fluorescent beads embedded in scattering phantoms and demonstrate that EDoF-Miniscope facilitates deeper interrogations of neuronal populations in a 100-μm100-μm<math><mrow><mn>100</mn><mtext>-</mtext><mi>μ</mi><mi>m</mi></mrow></math>-thick mouse brain sample and vessels in a whole mouse brain sample. Conclusions: Built from off-the-shelf components and augmented by a customizable DOE, we expect that this low-cost EDoF-Miniscope may find utility in a wide range of neural recording applications.