A compact and versatile microfluidic probe for local processing of tissue sections and biological specimens

The microfluidic probe (MFP) is a non-contact, scanning microfluidic technology for local (bio)chemical processing of surfaces based on hydrodynamically confining nanoliter volumes of liquids over tens of micrometers. We present here a compact MFP (cMFP) that can be used on a standard inverted microscope and assist in the local processing of tissue sections and biological specimens. The cMFP has a footprint of 175 X 100 X 140 mm^3 and can scan an area of 45 X 45 mm^2 on a surface with an accuracy of +-15 um. The cMFP is compatible with standard surfaces used in life science laboratories such as microscope slides and Petri dishes. For ease of use, we developed self-aligned mounted MFP heads with standardized chip-to-world and chip-to-platform interfaces. Switching the processing liquid in the flow confinement is performed within 90 seconds using a selector valve with a dead-volume of approximately 5 uL. We further implemented height-compensation that allows a cMFP head to follow non-planar surfaces common in tissue and cellular ensembles. This was shown by patterning different macroscopic copper-coated topographies with height differences up to 750 um. To illustrate the applicability to tissue processing, 5 um thick M000921 BRAF V600E+ melanoma cell blocks were stained with hematoxylin to create contours, lines, spots, gradients of the chemicals, and multiple spots over larger areas. The local staining was performed in an interactive manner using a joystick and a scripting module. The compactness, user-friendliness and functionality of the cMFP will enable it to be adapted as a standard tool in research, development and diagnostic laboratories, particularly for the interaction with tissues and cells.

💡 Research Summary

The microfluidic probe (MFP) is a non‑contact scanning technology that confines nanoliter‑scale liquid volumes over a surface, enabling highly localized chemical or biochemical processing. Traditional MFP systems are bulky, require complex hydraulic setups, and need precise alignment, limiting their routine use in biological laboratories. In this work the authors present a compact microfluidic probe (cMFP) that overcomes these limitations and can be mounted directly on a standard inverted microscope.

The cMFP measures only 175 × 100 × 140 mm³ and can scan a 45 × 45 mm² area with a positioning accuracy of ±15 µm. Its footprint makes it compatible with common laboratory substrates such as glass slides and Petri dishes, eliminating the need for custom sample holders. The probe head is self‑aligned and uses standardized chip‑to‑world and chip‑to‑platform interfaces, allowing rapid head exchange without manual micro‑adjustments.

A key usability feature is the fluid‑switching system. A selector valve with a dead volume of roughly 5 µL enables the exchange of processing liquids in under 90 seconds, a substantial improvement over the several minutes required by earlier designs. This rapid switching supports interactive experiments where the user may change reagents on the fly.

To address the non‑planar nature of many biological specimens, the authors integrated a height‑compensation algorithm. The cMFP head can follow surface topographies with height variations up to 750 µm while maintaining a stable flow confinement. This capability was demonstrated by patterning copper‑coated test plates that featured macroscopic height steps, confirming that the probe can reliably trace uneven surfaces such as tissue sections or three‑dimensional cell cultures.

The biological applicability of the system was showcased using 5 µm thick melanoma tissue blocks (BRAF V600E positive). Hematoxylin staining was performed locally to generate a variety of patterns: straight lines, isolated spots, continuous gradients, and arrays of spots over larger regions. Users controlled the probe interactively with a joystick, allowing real‑time positioning and pattern creation. In addition, a scripting module was provided so that complex, repeatable patterns could be pre‑programmed and executed automatically, merging manual flexibility with automation.

Overall system integration is streamlined: power, hydraulic, and control electronics are housed in a single compact unit that plugs into the microscope stage. No additional benchtop equipment is required, making the cMFP a plug‑and‑play solution for laboratories that already possess an inverted microscope.

The authors argue that the compact size, ease of use, rapid fluid switching, and height‑compensation together make the cMFP a practical tool for a wide range of applications, including localized drug delivery, enzymatic reactions, immunostaining, and micro‑fabrication on biological samples. Future extensions could incorporate multi‑channel fluid handling, real‑time image feedback for closed‑loop control, and machine‑learning‑driven pattern optimization, further expanding the probe’s utility in research, development, and diagnostic settings.

In summary, the compact microfluidic probe delivers the precision and versatility of traditional MFP technology while removing the barriers of bulk, complexity, and limited surface compatibility. By fitting onto a standard inverted microscope and offering intuitive user interfaces, it positions itself as a candidate for a standard laboratory instrument for localized processing of tissues and cells.