HologLev: A Hybrid Magnetic Levitation Platform Integrated with Lensless Holographic Microscopy for Density-Based Cell Analysis

Abstract

In clinical practice, a variety of diagnostic applications require the identification of target cells. Density has been used as a physical marker to distinguish cell populations since metabolic activities could alter the cell densities. Magnetic levitation offers great promise for separating cells at the single cell level within heterogeneous populations with respect to cell densities. Traditional magnetic levitation platforms need bulky and precise optical microscopes to visualize levitated cells. Moreover, the evaluation process of cell densities is cumbersome, which also requires trained personnel for operation. In this work, we introduce a device (HologLev) as a fusion of the magnetic levitation principle and lensless digital inline holographic microscopy (LDIHM). LDIHM provides ease of use by getting rid of bulky and expensive optics. By placing an imaging sensor just beneath the microcapillary channel without any lenses, recorded holograms are processed for determining cell densities through a fully automated digital image processing scheme. The device costs less than $100 and has a compact design that can fit into a pocket. We perform viability tests on the device by levitating three different cell lines (MDA-MB-231, U937, D1 ORL UVA) and comparing them against their dead correspondents. We also tested the differentiation of mouse osteoblastic (7F2) cells by monitoring characteristic variations in their density. Last, the response of MDA-MB-231 cancer cells to a chemotherapy drug was demonstrated in our platform. HologLev provides cost-effective, label-free, fully automated cell analysis in a compact design that could be highly desirable for laboratory and point-of-care testing applications.

Biomedical Applications of Magnetic Levitation

“…B) Illustration of the lensless MagLev design. [ 50 ] Reproduced with permission. [ 50 ] Copyright 2021, American Chemical Society.…”

“…[ 50 ] Reproduced with permission. [ 50 ] Copyright 2021, American Chemical Society. C) (left) The two‐ring axial MagLev design [ 34 ] and (right) single‐ring MagLev.…”

“…A challenging task in this method is the thresholding because reconstructed holographic images generate an optical artifact presented in LDIHM accompanying severe irregular background noise. [ 50 ]…”

“…An automated MagLev platform with LDIHM was designed for label‐free separation of three various cell lines (i.e., MDA‐MB‐231 [breast cancer cells], D1 [bone marrow stem cells], and U937 [monocytes]) and comparing them to their dead correspondents ( Figure 6 ). [ 50 ] The imaging was based on interferometry, meaning that the undistorted incoming light and the diffracted light from the sample would meet at the sensor to realize an interference (hologram) pattern. Two N52 NdFeB magnets (50 × 2 × 5 mm 3 ), with a separation gap of <1 mm, were used in a stereolithography‐based 3D printed framework.…”

“…With this device, it was possible to acquire high‐resolution images (<2 μm) without costly optical platforms, making this tool useful for portable and affordable point of care (PoC) medical applications. [ 50 ]…”