January 17, 2012 — IBM (NYSE: IBM) scientists have developed a flexible, non-contact, silicon microfluidic probe to accurately stain tissue sections at the micrometer scale for drug discovery and disease diagnostics research.
Tissue staining is widely used in pathology to detect disease markers in a patient’s sample. Traditional staining involves multiple chemical steps and precise exposure times. Mistakes at tissue staining can lead to false diagnoses. Biopsy samples are typically a few millimeters long. Staining is performed on many thin slices of the sample to identify and sub-type diseases.
The probe developed by IBM will "ensure a high diagnostic capability while minimizing patient discomfort," said Prof. Dr. Ali Khademhosseini, Associate Professor at Harvard Medical School and Brigham and Women’s Hospital. The probe stains a very small section of tissue with virtually any biomarker. Multiple stains can be used on the same sample.
The 8mm-wide, diamond-shaped probe comprises a silicon microfluidic head with 2 microchannels at each tip (See Figure 1). The head injects the liquid on the surface, then continuously aspirates the liquid to prevent spreading and accumulation on the surface, which can lead to overexposure.
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| Figure 1. The probe is similar to an inkjet head; however, unlike an inkjet printer cartridge, the head re-aspirates the liquid that it injects on a surface. |
For tissue section analysis, the probe can deliver an antibody very locally in a selected area of a tissue section with pinpoint accuracy. Since analysis can be done on spots and lines instead of on the entire tissue section, the tissue is better preserved for additional tests, if required. In addition, only a few picoliters (one trillionth of a liter) of liquid containing antibodies are needed for each analysis spot.
The microfluidic probe fits to standard workflows in conventional pathology. In addition, it is compatible with current biochemical staining systems and is resistant to a broad range of chemicals. The small size of the probe also enables easy viewing of the sample from above and below by an inverted microscope commonly used in research and clinical laboratories. Pathology can be put on a "modern roadmap," thanks to "the latest developments in silicon-based microfluidics," said Govind Kaigala, a scientist at IBM Research – Zurich. Also read: Microfluidics: $4B in 2016, thanks to life sciences
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| Figure 2. Marios Georgiadis, currently a PhD student at ETH Zurich, Institute for Biomechanics, takes a closer look at a silicon wafer containing dozens of microfluidic probes. |
Prof. Dr. Khademhosseini said, "The developed system may have great potential in applications where sample size and the need for testing various types of biological analysis are required. I am confident that one day such approach will enable us to take small tissue biopsies and be able to obtain significantly more information."
IBM scientists will continue to test and improve the probe and potentially begin using it in laboratory environments in the next several months. The team plans to explore specific clinical applications, possibly with partners in the field of pathology.
IBM’s work is reported in the peer-reviewed journal Lab on a Chip. The scientific paper entitled "Micro-immunohistochemistry using a microfluidic probe" by Robert D. Lovchik, Govind V. Kaigala, Marios Georgiadis and Emmanuel Delamarche, appears at http://pubs.rsc.org/en/content/articlelanding/2012/lc/c2lc21016a.
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| Figure 3. A concept and workflow of micro-immunohistochemistry (μIHC) using a vertical microfluidic probe (vMFP). Dewaxing and rehydration of the tissue are performed according to conventional IHC (1). Using injection and aspiration apertures at the apex of a vMFP head, a solution of primary antibody is hydrodynamically confined (in the presence of an immersion liquid) to selected areas of a tissue section (2). Post-processing for visualization of the antigens on the tissue section continues as in standard IHC: the tissue section is incubated with secondary antibodies, and enzymatic precipitation of 3,3′-diaminobenzidine (DAB) chromogen leads to a visual signal, indicating the expression level of specific antigens in the tissue section semi-quantitatively. Typical parameters for the vMFP scans are indicated. Source: Lab on a Chip, DOI:10.1039/C2LC21016A |
See all the photos from the microfluidic probe development on Flickr
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