Liquid Crystal Technology
CDx Liquid Crystal and LC Buffer

Crystal Diagnostics has exclusive world-wide rights to patents for liquid crystal technology developed by Northeast Ohio Medical University and Kent State University. The Company’s intellectual property includes exclusive licenses to 14 United States issued patents and 5 foreign issued patents. Additionally, Crystal Diagnostics has independently filed for two utility patents.

The licensed base patents cover three key areas: (1) the use of lyotropic chromonic liquid crystals as the amplification media for detection (if a ligand is created within the liquid crystal, the liquid crystal is disrupted, amplifying the size of the ligand and allowing detection); (2) a multi-chamber cassette used as the delivery and repository for the detection process (i.e. the razor-blade); and (3) the detection and amplification of ligands (i.e. the use of antibody covered microspheres as targets for aggregation and detection).

Excerpts from selected CDx patents:

United States Patent # 6,673,398 – Alignment of lyotropic chromonic liquid crystals at surfaces as monolayers and multilayered stacks

Lyotropic chromonic liquid crystals changing phase @ 20X magnification

A broad class of lyotropic liquid crystals of a non-surfactant nature, the so-called lyotropic chromonic liquid crystals (LCLCs), are alignable with the techniques, in particular, LCLCs can be aligned at a surface as one monomolecular layer as a stack of monomolecular layers. The feature of controlling the alignment of LCLCs enables one to create practical devices from them.

To create oriented monolayers of LCLC, the following steps are performed. First, a liquid crystal composition is prepared by dissolving a sufficient amount of a lyotropic chromonic liquid crystal material in deionized water. The thermodynamically stable state of the material is thus the one with long-range orientational order both in the bulk and at the surfaces. Next, a substrate is prepared by covering it with a polyion. The polarity of the polyion is opposite to that of the charged chromonic molecules. The LCLC is then deposited on the substrate in a unidirectional manner.

United States Patent # 7,060,225 – Self-contained assay device for rapid detection of biohazardous agents

Automated UV conveyor curing system for BioCassette assembly

A self-contained device, called an assay cassette, for rapid, safe, and automatic detection of biohazardous ligands. The cassette comprises one or more mixing chambers configured for mixing various assay components with an introduced sample, such assay components being a receptor (e.g., an antibody) capable of binding to the ligand, an optional generally spherical particle capable of binding to the receptor (e.g., microspheres coated with antibody); and a liquid crystalline material. A device for detecting a signal that is transmitted through the detection chamber of the assay cassette (i.e., a reader device). The device is also configured to provide for laminar flow of the mixed sample into the detection chambers such that the liquid crystalline material assumes a uniform alignment with the director except when adjacent to an inclusion body whose diameter exceeds the critical diameter e.g., surrounding immune aggregates. The local liquid crystal distortions allow transmission of spots of polarized light through the detection chamber for identification by a photo-detector.

A device for detecting the presence of a ligand in a sample, comprising, a cassette having a first and a second end, and comprising an inlet port at the first end which is in fluid communication with at least one flow channel, said flow channel(s) comprising, one or more mixing chambers, one or more assay components, and a detection chamber delineated on at least two sides by low or non birefringent glass and in fluid communication with the one or more mixing chambers.

United States Patent # 6,171,802 – Detection and Amplification of Ligands

Actual 1/4 VGA image of liquid crystal amplification of a positive test

The detection of a ligand by a receptor, for example, detection of a pathogenic agent such as a microbe or toxin by an antibody; or detection of an antibody in blood by another antibody; or binding of a chemical toxin, such as nerve gas, to its receptor. Any receptor, such as antibodies or biologic/biologically engineered receptors for ligands, can be incorporated into the device as long as binding of the ligand to the receptor causes a detectable distortion of the receptor. For example, any type of monospecific antibody (polyclonal, monoclonal, or phage displayed) can effectively function as a receptor.

Any mechanism that permits detection of ligand-receptor complex formation functions as an amplifier and can be incorporated into the device. Specifically, a liquid crystal will amplify the distortion caused when a ligand binds to a receptor. A liquid crystal is a state of matter in which molecules exhibit some orientational order but little positional order. This intermediate ordering places liquid crystals between solids (which possess both positional and orientational order) and isotropic fluids (which exhibit no long-range order). Solid crystal or isotropic fluid can be caused to transition into a liquid crystal by changing temperature (creating a thermotropic liquid crystal) or by using an appropriate diluting solvent to change the concentration of solid crystal (creating a lyotropic liquid crystal). Lyotropic liquid crystals will be used for our amplification system.