Paper-Based Biosensors: Design, Analysis, and Applications

Paper-Based Biosensors

Immunosensors

Immunosensors are affinity ligand-based biosensor solid-state devices in which the immunochemical reaction is coupled to a transducer. The fundamental basis of all immunosensors is the specificity of the molecular recognition of antigens by antibodies to form a stable complex.

Paper-Based ELISA

There are different techniques for the design and development of immunoassays. For instance, combining ELISA (Enzyme-Linked Immunosorbent Assay) and patterned paper provides a beneficial protocol for performing immunoassays.

Advantages and Disadvantages of Paper-Based ELISA

Paper-based ELISA offers three principal advantages over conventional ELISA performed in plastic 96-well plates:

• More rapid detection.
• Requires only small volumes of samples and reagents.
• Utilizes simple equipment.

However, a key disadvantage of paper-based ELISA is that it is less sensitive than conventional ELISA.

Material Properties of Paper

Paper is a well-known material used for writing, drawing, printing, and packaging. The potential utility of paper beyond these simple applications stems from its physical properties. It is a highly sophisticated material that can be thin and flexible.

Paper consists of cellulose fibers. Cellulose is the Earth’s most abundant biopolymer, made up of a long chain of glucose molecules linked by oxygen bridges. This property is highly attractive for certain applications, as it allows liquid to penetrate within its hydrophilic fiber matrix without the need for an active pump or external source. In addition, cellulose fibers can be functionalized, allowing properties such as hydrophilicity, permeability, and reactivity to be modified.

ASSURED Criteria for Diagnostics

The ASSURED criteria define the ideal characteristics for diagnostic tools, especially those used in resource-limited settings:

• Affordable
• Sensitive
• Specific
• User friendly
• Rapid and Robust
• Equipment free
• Delivered (meaning deliverable to those who need it)

Microfluidic Paper-Based Analytical Devices (μPADs)

μPADs involve fabricating microfluidic channels on paper for multiplex analyte detection. The method is typically based on colorimetry, which measures color intensity in relation to the concentration of the analyte. With these paper-based devices, assays can be performed without using pipettes, syringes, needles, pumps, or external electric energy.

Fabrication Methods for Paper Patterning

Common techniques used for patterning paper and fabricating biosensors include:

• Wax printing
• Solid Ink Printing
• Photolithography
• Cutting (e.g., mechanical cutting)
• Laser cutting

Quantitative Analysis and Transduction Methods

In order to create an effective analytical device, suitable transduction methods are necessary. To maintain simplicity, affordability, and portability, low-power techniques such as optical and electrochemical methods are well suited as transducers.

The five most commonly reported techniques for quantitative analysis on paper are:

1. Colorimetric detection
2. Electrochemical methods
3. Chemiluminescence
4. Electrochemiluminescence
5. Electrical conductivity

Applications of Paper-Based Sensors

Paper-based sensors are highly valuable for use at home and in resource-limited regions, with key applications including:

• Clinical diagnostics
• Environmental screening
• Food safety inspection