Technology

“The reliable detection of molecular interactions in the life sciences might take an unexpected high-tech turn: Lithography on a nanometre scale makes it possible to distinguish between specific and non-specific binding on the surface of a chip.”
Dr. Christof Fattinger; 2016
This “high-tech turn” was achieved in 2019 and lino Biotech was founded to unleash the potential of diffractometric biosensors for sensitive and robust diffractometric biomolecular interaction analysis.

Focal Molography

In short, focal molography is a nanotechnology-based method that cleverly combines photolithography, molecular self-assembly and state-of-the-art optical technology. It is a truly interdisciplinary technology, inspired by physics, tailored for biology and implemented for biomolecular interaction analysis.

Central to the technology is a biological surface structure termed mologram, which is part of our patented sensor chip. Bound biomolecules on the mologram function as “detectives” that recognize the target analyte in the sample through molecular recognition and selective binding and thereby emit a light signal.

This signal indicates the exact measure of binding affinity between recognition site and analyte. This coherent signal is measured in the molographic focus by the instrument’s detector array. One diffraction-limited mologram spot, less than one micrometre in diameter, represents one binding signal. Multiple molograms can be assembled on a tiny chip, meaning that multiple parameters can be measured swiftly, with great selectivity and sensitivity.

“The reliable detection of molecular interactions in the life sciences might take an unexpected high-tech turn: Lithography on a nanometre scale makes it possible to distinguish between specific and non-specific binding on the surface of a chip.”
Dr. Christof Fattinger; 2016
This “high-tech turn” was achieved in 2019 and lino Biotech was founded to unleash the potential of diffractometric biosensors for sensitive and robust diffractometric biomolecular interaction analysis.

Focal molography – a new method for Biomolecular Interaction Analysis (BIA)

Biomolecular interaction analysis (BIA), i.e. the direct and label-free monitoring of binding events between molecules on a sensor surface, is a key method in molecular biology. Over the past 30 years, refractometric biosensors, and in particular surface plasmon resonance (SPR), have matured to the de facto standard of BIA despite their significant cross reactivity to environmental and experimental noise sources.

Two publications regarding focal molography introduce and demonstrate the concept of the “spatial affinity lock-in” as a novel design principle to overcome the drawbacks of established BIA methods. The spatial affinity lock-in is analogous to the time-domain lock-in. Instead of a time-domain signal, it modulates the binding signal at a high spatial frequency to separate it from the low spatial frequency environmental noise in Fourier space. Focal molography applies this fundamental detection principle to BIA.

Combined with the right surface chemistry and recognition elements on the sensor surface focal molography enables robust, sensitive and fundamentally new BIA assays such as the direct and label-free monitoring of biomolecular interaction on the cell membrane.
Further reading: Ultra-stable molecular sensors by sub-micron referencing and why they should be interrogated by optical diffraction —

Part I. The Concept of a Spatial Affinity Lock-in Amplifier:

https://www.mdpi.com/1424-8220/21/2/469

Part II. Experimental Demonstration:

https://www.mdpi.com/1424-8220/21/1/9