A new method for accurately measuring the bending of nano and micron-sized components in diagnostic sensors has been developed by researchers at the London Centre for Nanotechnology.
The method, published in the journal Applied Physics Letters, significantly simplifies the detection of mechanical perturbations, by enabling simultaneous measurement from an array of cantilevers. In doing so, the LCN technique can provide a solution to the challenging problem of multiplexed diagnostics.
Micro-cantilevers are one of the simplest and most common examples of micro systems technology. These devices are designed to respond to minute mechanical changes, and are routinely used in a range of different technologies, such as accelerometers in mobile phones and high-resolution microscopy.
Cantilever arrays can also be applied to a variety of diagnostic tests, including medical diagnostics, food safety, and water quality or threat detection. The surface of each individual cantilever can be modified to detect a particular molecule, for example a specific antibody. As a target molecule attaches to the cantilever, it bends. This bending can be measured to confirm the molecule’s presence and estimate its quantity.
In current diagnostic systems utilising micro-cantilevers, the change in the state of a cantilever due to the presence of a target molecule is read by illuminating each cantilever individually. This introduces the complexity of aligning the illumination beam with each individual sensor, making it tedious and prone to errors.
The LCN method removes the need to align the beam, illuminating a whole cantilever array with a single, broad laser beam and recording a “picture” of the resulting diffraction pattern. The bending of the cantilever is revealed in greater detail by the details of a diffraction pattern, showing tilt, curvature, cubic and higher order bending. The highly accurate system is robust to misalignment as the qualities measured, such as size and shape, are independent to their position in the image.
The unique benefit of this approach is using a single detector for the simultaneous measurement of several markers (multiplexed detection), as for example in HIV diagnosis, where viral load and antibody concentrations could be obtained in one step using this method. The LCN has now designed and constructed a compact table-top prototype that incorporates this novel detection technique along with a state-of -the-art automatized fluid delivery system. It is thought that this technology has potential to be miniaturized at low cost, enabling future development of sophisticated point-of care devices.
Dr. Rodolfo Hermans, lead author of the paper, said "Simple systems work every time and we have solved a detection problem by reducing the complexity of the hardware and therefore making it more reliable”.
The LCN method is the subject of a patent application filed in conjunction with UCL Business, the technology transfer office of UCL.
Figure: The method is based on the observation that the size of the diffraction pattern produced by the light reflected from a curved micro-structure is proportional to the curvature. The background of the figure shows the calculated pattern, from the left a concave structure and to the right, a convex structure. In the foreground the figure shows our fully functional instrument prototype.