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Novel highly sensitive NanoWire sensors for disease biomarker analysis

Periodic Reporting for period 1 - NanoWi (Novel highly sensitive NanoWire sensors for disease biomarker analysis)

Reporting period: 2022-06-01 to 2023-05-31

Early diagnosis of many diseases, such as cancer, significantly improves their prognoses, directly impacting patient survival. Early diagnosis relies on successfully detecting the presence of biomarker molecules, which are often difficult to quantify (due to their low concentration) and represent a time-consuming process. Several technology platforms have been emerging as promising tools for high-throughput analysis of biomarkers. However, few have translated into clinical practice due to two major limitations: i) insufficient sensitivity for multiplexing and ii) weak signal-to-noise ratio, both contributing to Limits of Quantitation above the clinically useful values. 3D NW-platforms can greatly impact disease diagnosis and precision medicine thanks to their high surface-area-to-footprint ratio and optical waveguiding properties. However, the challenge is to cost-effectively produce NWs in a reproducible manner at large scale, for them to become commercially viable.
At Aligned Bio, we are developing the most advanced and customizable NW sensors for use in assay platforms, enabling reproducible results, a 20-times increase in sensitivity over results of current biomarker detection assays, and at a cost that makes mass-scale production feasible. Whereas standards biomarker assays rely on flat surface for detection, 3D NW platforms present a high surface-area-to-footprint ratio effectively increasing the available sensing area thus the number of biomarkers immobilized on the platform. In addition, NWs show a critical optical waveguidance effect, which enables the generation, and subsequent detection, of a signal more than an order of magnitude higher than the one generated by planar platforms. Leveraging on Aligned Bio proprietary NW production technology (Aerotaxy™) and alignment method, we will allow, for the first time, the use of NW for biosensing purposes, and thus the next generation 3D NW platforms to become commercially viable.
Achievements:
- Assembly of ATXY beta tool
- Growth of GaP NW using ATXY
- Production of ≥90% aligned nanowires over 1mm2 using wafer-based NW Si nanowire
- Transition from GaP to Si NW without loss of functionality
We will develop a technology that allows us to vertically align (≥90% alignment) GaP NWs at the correct spacing in a polymer filmand on a large scale. We will also develop the properties of the polymer,so the material is suitable for the application. This typically involves making sure the autofluorescence is low enough so sensitivity is not affected, and that the surface properties (hydrophilicity/-phobicity) are not interfering with the application(e.g. needing a hydrophobic polymer in the case of spotting, or a hydrophillic polymer in the case of a multi-well plate). - This work is in progress. We already achieved >90% alignment and polymer properties are being optimized.

We need to improve upon the design and develop three main physical components for Aerotaxy™. Specifically, we need to revise/test the particle source generator, the particle size selection tool (Differential Mobility Analyzer, DMA), and the reactor itself. These need to be developed for the purpose of growing GaP NWs in a manner that meets the outlined specifications. To accomplish this, we also need to add to our in-house knowledge on the nucleation and growth mechanisms within the system. We will work with the CFD and engineering consultants to optimize gas flows, gas inlet placements and flow speeds to ensure proper length, axial growth and kink minimalization. We will
also look to ensure that these conditions are met while guaranteeing clogging rates that are reasonable for the targeted uptimes. In addition to the optimization of the Aerotaxy™ tool we will implement and optimize a design we purchased as part of our alignment IP for a large-scale alignment production tool. - For the first time ever, we have produced GaP NW using the current ATXY system. This shows that ATXY is technically capable of producing GaP nanowires, although not currently to target specifications. We will continue developing ATXY as future applications could require specifications only possible to reach with ATXY, but delays are significant and ATXY will not deliver within project time.