The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research.
The proposed integration of microfluidic techniques and tissue slice samples is called “tissue microfluidics” because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets.
The proposed principles represent a paradigm shift in microfluidic technology in three important ways:
- Microfluidic devices are to be directly integrated with, onto, or around tissue samples, in contrast to the conventional method of off-chip sample extraction followed by sample insertion in microfluidic devices.
- Architectural and operational principles of microfluidic devices are to be subordinated to suit specific tissue structure and needs, in contrast to the conventional method of building devices according to fluidic function alone and without regard to tissue structure.
- Sample acquisition from tissue is to be performed on-chip and is to be integrated with the diagnostic measurement within the same device, in contrast to the conventional method of off-chip sample prep and subsequent insertion into a diagnostic device. A more advanced form of tissue integration with microfluidics is tissue encapsulation, wherein the sample is completely encapsulated within a microfluidic device, to allow for full surface access.
The immediate applications of these approaches lie with diagnostics of tissue slices and biopsy samples — e.g. for cancer — but the approaches would also be very useful in comparative genomics and other areas of fundamental research involving heterogeneous tissue samples.
The approach advocates and utilizes the bottom-up customization of microfluidic architectures to biosamples, in contrast to the traditional top-down approach of building the architectures first and then putting the biosamples inside. Further, as particular embodiments of the above principle, novel techniques of sub-sample selection and isolation are presented. These techniques would have wide applicability in fundamental research and biomedical diagnostics.
In particular, an in situ microfluidic technique of single-cell isolation, or multiple single-cell isolations, is described, and is performed upon tissue sections attached to pathology glass slides. The technique combines the advantages of preserving the architectural integrity of the tissue section while allowing flexibility and precision of cell selection, rapid prototyping, and enhanced sample purity, while benefiting from the experience of the pathologist in the selection process. The result is a system that would allow the rapid and reliable biochemical analysis and diagnosis of pathologic processes with sensitivity extended down to the level of even a single cell, with high levels of confidence in the diagnostic determination.
These techniques would allow the extraction of cells and cell nuclei chosen for their potentially pathologic origin, e.g. cancer. The chief advantages of the proposed methods are their speed, ease, reliability, and capacity to select individual cells from a tissue slice population with a higher degree of purity and specificity. The result is the extracted DNA can be biochemically analyzed with a higher degree of diagnostic accuracy, as the isolated sub-sample would not be diluted by unwanted material from the ambient tissue. In comparison to other techniques, the proposed methods would combine high specificity with high speed.
This work was done by Lawrence A. Wade of Caltech and Emil P. Kartalov, Darryl Shibata, and Clive Taylor of the University of Southern California for NASA’s Jet Propulsion Laboratory.
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