Microtomography for microfluidics at Photonics West

Microfluidics is a technique for controlling, processing, and analyzing small volumes of liquid in submillimeter devices. The small scale befits biology especially. Not only are cells and microorganisms themselves small, but they are often available only in small, precious quantities.

Monitoring a microfluidic device is usually done through an optical microscope, which is typically a hundred times as big as the device itself. What’s more, because conventional microscopes rely on lenses, high spatial resolution is obtained at the expense of a small field of view. Paradoxically, big microscopes yield small images.

At this year’s SPIE Photonics West , graduate student Serhan Isikman from Aydogan Ozcan’s biophotonics lab at UCLA described a lensless tomographic imaging system whose 4- by 6-mm CMOS sensor array is not much bigger than a typical microfluidic device. Like a hospital CT scanner, the UCLA imager takes multiple two-dimensional images from which 3D images are reconstructed. Isikman and Ozcan call the technology optofluidic tomography.

The figure shows the basic principle. Each 2D image consists of a so-called in-line hologram. Spherical wavefronts emanate from a coherent light source and either pass right through the objects in the microfluidic device or are scattered and absorbed by them. What the CMOS sensor records is the interference pattern formed by the unaffected and affected wavefronts. The 2D image is reconstructed directly from the hologram (that is, the interference pattern) without the need to send a second reconstruction beam through the hologram, as is the case in standard “off-line” holography.

The 2D images are created in quick succession by a bank of LEDs arranged in a circular arc above the microfluidic device. A second round of reconstruction, called filtered back projection, is used to create a 3D image from the 2D images.

Because the UCLA system lacks magnification, its spatial resolution is ordinarily limited by the pixel size of the sensor, 2.2 μm. But finer resolution can be obtained thanks to a technique called pixel superresolution (PSR). Assuming that an object doesn’t change size or shape as it passes over a patch of pixels, you can use the signals recorded in the pixels to interpolate the object’s shape. If the object is stationary, rocking the light sources with electromagnetic actuation enables PSR to be applied.

Using PSR, Isikman, Ozcan, and their colleagues have obtained a resolution of less than 1 μm. That’s comparable to the resolution of an optical microscope, but it’s achieved over a bigger field of view (about 100 times as wide as an optical microscope at ×40 magnification). Despite its significantly enlarged field of view, the lensless tomographic microscope can fit in a small volume of 96 × 89 × 40 mm, and weighs only about 110 grams.

In his talk, Isikman reported results of imaging two microorganisms, the nematode worm and model invertebrate Caenorhabditis elegans and the eggs of the dwarf tapeworm Hymenolepis nana.

The lensfree tomography and computational microscopy work of Ozcan’s bio-photonics lab has yielded several patent applications over the last few years. They’re licensed by Holomic LLC , a startup based in Los Angeles.