Nowadays, doctors usually collect serum from patients in the hospital for various examinations. Such as tumour detection [1–3] and virus detection [4–6] etc. The preliminary method for tumour detection is protein detection, because proteins are the components of many tumour markers, and these biomolecules with a lot of information exist in the serum. Serum albumins are the most abundant (52–62%) total water-soluble fraction proteins in the blood plasma [7, 8]. Furthermore, nutritional and physiological functions of serum albumins make them as essential bio-macromolecules. As one of the most popular serum albumins, bovine serum albumin (BSA) is used in a lot of research fields. Therefore, the research on the detection of BSA is quite important. There are many methods for detecting and determining the concentration of BSA, including electrochemical impedance spectroscopy [9], capillary electrophoresis [10], and light scattering techniques [11]. But they all have some disadvantages, such as complicated procedures, poor reproducibility or time-consuming. Therefore, developing new biosensors is of considerable significance and quite in demand.
The THz wave is between the microwave and infrared optical wave and in the transition region from electronics to photonics. Compared with light waves, the energy of photons in this band is very low. This means that terahertz waves will not cause radiation ionization damage to biological molecules. Many biological macromolecules also have unique fingerprints in the terahertz band [12–15]. Therefore, terahertz waves have received considerable attention in the field of biosensing [16, 17].
Metamaterials are artificial electromagnetic materials composed of subwavelength structures. Their unique electromagnetic resonance has many characteristics, such as a negative RI [18, 19], electromagnetically induced transparency [20, 21], and extreme environmental sensitivity [22, 23]. Metamaterials sensitive to the surrounding environment, especially those composed of subwavelength metal structures [24–26], have been widely used to detect various biomolecules. The combination of terahertz waves and metamaterials provides a new detection method for the biomedical molecules, which cannot only achieve label-free detection, but also refresh the resolution limit of existing sensors. In addition, detection can be completed simply and rapidly using a small amount of analyte with no chemical reagents.
At THz frequencies, metamaterial production usually relies on micron-level processing methods. Photolithography [27] or electron beam lithography [28] is mainly used to transfer micro-nano patterns from the photoresistor to the surface of the functional materials, and then wet [29, 30] or dry etching [31, 32] is required to complete the final processing of the metamaterials. Through the above steps, the construction of fine graphics can be achieved, but unfortunately, most of these methods demand expensive processing equipment, high standard operation environments, and cumbersome processing procedures. Laser drilling [33] is the first practical laser processing technology, and it is also one of the main application fields of laser processing. The laser beam is highly concentrated in space and time. By focusing with a lens, the spot diameter can be reduced to micron level, and the laser power density of 105 − 1015 W / cm2 can be obtained. With such a high-power density, laser drilling can be carried out in almost any material. To the best of our knowledge, this is the first time to apply laser-drilling technology in the fabrication of metamaterial biosensors, which can significantly reduce the processing cost of metamaterial biosensors and promote their practical applications.
In this study, a highly sensitive terahertz biosensor for protein detections based on all-metal metamaterial was proposed, theoretically simulated and experimentally demonstrated. The device was simple to manufacture, cost-effective and quite stable. It was composed of stainless-steel material and manufactured using laser-drilling technology. At first, this metamaterial sensor was simulated and analyzed using the finite integral method, and the refractive index sensitivity was calculated. Then this THz metamaterial biosensor was fabricated and measured. The experiments confirmed the high sensitivity of this senor to external environment. BSA was chosen as the detection substance to assess the biosensor’s effectiveness. The Hill formula was used to fit the experimental data. A detection sensitivity of 72.81 GHz/(ng/mm2) and the limit of detection (LOD) of 0.035 mg/mL were obtained. The measurements were repeated three times to verify the biosensor’s reliability.