New-Tech Magazine - Europe | January Digital edition

Figure 1: ‘Cell sorter’ chip that identifies and sorts 3,000 cells per second

Figure 2: Concept of the high-throughput ‘cell sorter’ chip

to investigate, it is separated in a distinct microfluidic channel. This is done with the help of steam bubbles generated with heating elements In the different output channels, the live cells are collected for further examination A smart combination of silicon technology, lens free microscopy and ultrasmall steam bubbles The ‘cell sorter’ chip is fabricated in silicontechnology,thesametechnology also used to make computer and memory chips. One of the advantages is that all building blocks can be mass- produced extremely compact and be integrated in a cost-efficient way. This cost advantage becomes even greater if more, parallel sorting structures are integrated on the chip. For visualizing and identifying cells, the cell sorter uses lens-free digital holographic microscopy. A laser on top of the microfluidic channel illuminates the cells as they pass. An image sensor placed under the channel captures the interference pattern of the laser light and the light that has passed through the cells. With this interference pattern, an image of

the cell can be reconstructed. The image quality is comparable to that of phase contrast microscopy. We optimized this technology, improving the resolution considerably by using a light point source (which creates a ‘zoom’ effect). Experiments with blood samples have shown that this technique allows to distinguish between three major classes of white blood cells: granulocytes, monocytes, and lymphocytes. These types differ in their size and granularity of the cell contents. In the experiments, we first looked at samples that contain only one type of cell. This allowed to optimize the classification algorithm. Next, we analyzed a full blood sample, with the results shown in figure 5. These results are highly comparable with those obtained with a clinical hematology analyzer (figure 6), which proves the validity of the lens-free microscopy technique. The microfluidic switch that we use to separate the cells of various types is based on small, starlike heating elements (figure 7). Our prototype contains 288 such elements, situated

hospitals, remote points of care, or at the doctor’s practice.

A concept comes alive The idea for the high-throughput ‘cell sorter’ chip was developed two years ago (see https://vimeo. com/82078661 and figure2). R&D manager Liesbet Lagae was awarded a prestigious ERC-grant to further develop the promising idea. And imec scientists made the first building blocks and integrated them in a chip of 4cm x 2cm (figure3), with the following process for a cell analysis: A drop of blood is inserted into the input channel The cells move through a microfluidic channel with a high speed of a few meters per second One by one, the cells pass over an image sensor while they are illuminated by a laser Based on the holographic image on the sensor, a powerful computation chip reconstructs an image of each individual cell The cell is identified (a tumor cell, bacteria ...) If the cell is of a type that we want

New-Tech Magazine Europe l 31