3D-printed biosensors for high-sensitivity molecular detection

This invention describes the creation of highly sensitive biosensors through 3D printing using stereolithography (SLA). These biosensors, made from a biopolymer blend with specific monomers and a photoinitiator, are functionalized with recognition molecules to detect small and large analytes, including disease markers, in commercial well plates.

Background

Additive manufacturing, commonly known as 3D printing, is revolutionizing various industries by enabling the creation of complex and customized objects through the layer-by-layer deposition of materials. In the biomedical field, this technology holds significant promise for fabricating intricate devices such as biosensors, which are essential for detecting and diagnosing diseases. The need for advanced biosensors arises from the growing demand for precise, rapid, and sensitive detection of biological molecules, including proteins, nucleic acids, and small molecules. These sensors are crucial in medical diagnostics, environmental monitoring, and food safety, where accurate detection at low concentrations can lead to early disease diagnosis, effective treatment, and better health outcomes.

Despite the advancements in biosensor technology, current approaches face several critical challenges. Traditional methods of sensor fabrication often involve complex and time-consuming processes that limit the ability to produce sensors with customized shapes and sizes. Furthermore, the immobilization of recognition molecules, such as antibodies or nucleic acids, onto the sensor surface can be inefficient and inconsistent, leading to poor sensitivity and reliability. Issues such as non-functional immobilization, suboptimal surface regeneration, and the inability to detect multiple analytes simultaneously further hinder the effectiveness of these sensors. Additionally, many existing sensors struggle with achieving homogenous distribution of recognition molecules, which is vital for accurate and reproducible measurements. These limitations underscore the need for innovative manufacturing techniques that can overcome these barriers and enhance the performance of biosensors.

Technology description

The described technology involves a novel method for producing biosensors using additive manufacturing techniques, specifically stereolithography (SLA). These biosensors are crafted from a biopolymer formulation that includes a dimethacrylate monomer, one or more PEGylated diacrylate or dimethacrylate monomers, and a photoinitiator. The biopolymer shapes, such as cylinders, balls, or custom designs, are functionalized with recognition molecules like antibodies or nucleic acids, which are evenly distributed along the shape's height. Additionally, the biopolymer is treated with a polysaccharide polymer, such as chitosan, to facilitate the immobilization of the recognition molecules. These biosensors are designed to fit into commercial well plates, including 96 and 384 well plates, and can detect both small and large molecules with high sensitivity, down to picomolar concentrations. The technology also includes methods for detecting analytes in solutions and determining the presence of disease states in patients using these biosensors.

The differentiation of this technology lies in its integration of advanced materials and manufacturing techniques to achieve high sensitivity and specificity in molecular detection. By utilizing stereolithography, the biosensors can be produced with precise and customizable geometries, enhancing their functional capabilities and fitting them into standard laboratory equipment seamlessly. The use of a biopolymer formulation that includes PEGylated monomers and a photoinitiator ensures that the biosensors have the necessary mechanical properties and stability for reliable performance. The homogeneous distribution of recognition molecules along the height of the biosensor shapes, coupled with the immobilization facilitated by chitosan, ensures consistent and accurate detection of analytes. This combination of material science and additive manufacturing not only allows to produce highly sensitive biosensors but also enables the creation of custom shapes, tailored to specific diagnostic needs, setting this technology apart from conventional biosensor production methods.

Benefits

  • High sensitivity detection down to picomolar concentrations
  • Capable of detecting both small and large molecules
  • Customizable shapes for specific applications
  • Fit into commercial well plates (96 and 384 well plates)
  • Uses additive manufacturing techniques (stereolithography)
  • Homogeneous dispersion of recognition molecules
  • Facilitates immobilization of recognition molecules
  • Can determine the presence of disease states in patients
  • Reduces material depletion and production costs
  • Constructs small and intricate objects with high precision

Commercial applications

  • Medical diagnostics
  • Drug testing
  • Environmental monitoring
  • Food safety