TECHNICAL FIELD

Embodiments of the invention relate to microflakes encoded with digital codes and the fabrication process of the microflakes.

BACKGROUND

With the development of precision medicine, personalized medicine, and preventive medicine, there is a need in the field of in-vitro diagnosis (IVD) for performing assays on a large number of targets in biological test samples. A multiplex approach, known as multiplex assays, enables multiple measurements to be simultaneously performed on multiple different targets to increase test throughput and reduce cost. Multiplex assays have a wide range of applications such as pathological diagnosis (e.g., infectious disease or oncology), food safety, human and animal disease control, environmental monitoring, biomedical science research, drug screening and discovery, etc.

To conduct a multiplex assay, reagents such as probes are immobilized on the solid-phase surface of microcarriers. Depending on the type of the desired target, the probe can be an antibody, a protein, an antigen, a DNA, an RNA or another molecule with an affinity for the desired target. Microcarriers with different probes are added into a test sample, such that the probes and the corresponding targets in the test sample make specific bonding. Excess substances not bounded to any probes may be washed and removed. Detection antibodies or other suitable agents can be added to the targets to form specific bonding. These detection antibodies or suitable agents may contain a fluorophore, which emits light upon excitation by a light source. The emitted light allows those targets that are bounded to the probes to be observed and quantified.

A test sample in a multiplex assay typically contains multiple targets of interest. To keep track of which targets are bounded to the probes on the microcarriers, various approaches have been developed to encode microcarriers, such that microcarriers with different probes can be distinguished from one another.

For example, one approach is to label different microcarriers with different fluorescent dyes; however, the number of available fluorescent dyes is typically insufficient for multiplex assays where high throughput is desired. Another approach is to encode a microcarrier with a pattern of opaque segments and transparent gaps, where the pattern is enclosed within the microcarrier.

Conventional approaches such as the ones described above generally have several disadvantages such as high fabrication cost, insufficient reaction surface, poor performance, etc. Thus, there is a need for improving the design and fabrication of encoded microcarriers.

SUMMARY

In one embodiment, a microflake is provided. The microflake includes a polymer layer, which has a top surface and a bottom surface substantially parallel to the top surface. At least one of the top surface and the bottom surface is to be coupled to target-specific probes for bonding with a target analyte. The microflake is identified by a binary sequence of bits encoded by an edge outline on a plane substantially parallel to the top surface and the bottom surface. The bits in the binary sequence are encoded at respective predefined locations surrounding the edge outline.

In another embodiment, an apparatus for a multiplex assay is provided. The apparatus comprises a first microflake to form a target-specific bonding to a first target analyte, and a second microflake to form a target-specific bonding to a second target analyte which is different from the first target analyte. The first microflake is identified by a first binary sequence, and the second microflake is identified by a second binary sequence different from the first binary sequence. The first binary sequence is encoded by a first edge outline on a first plane substantially parallel to a top surface and a bottom surface of the first microflake, and bits in the first binary sequence are encoded at respective predefined locations surrounding the first edge outline. The second binary sequence is encoded by a second edge outline on a second plane substantially parallel to a top surface and a bottom surface of the second microflake, and bits in the second binary sequence are encoded at respective predefined locations surrounding the second edge outline.

In yet another embodiment, a semiconductor wafer is provided. The semiconductor wafer comprises a substrate; a plurality of first microflakes on the substrate; and a plurality of second microflakes on the substrate. Each first microflake is identified by a first binary sequence, and each second microflake is identified by a second binary sequence different from the first binary sequence. Each first microflake is identified by a first binary sequence encoded by a first edge outline on a plane substantially parallel to the substrate, and bits in the first binary sequence are encoded at respective predefined locations surrounding the first edge outline. Each second microflake is identified by a second binary sequence encoded by a second edge outline on the plane, and bits in the second binary sequence are encoded at respective predefined locations surrounding the second edge outline.

Other aspects and features will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments in conjunction with the accompanying figures.

