Shoji Hachuda

Super-sensitivity in label-free protein sensing using a nanoslot nanolaser

Microphotonic sensors have been actively studied with increasing demands for label-free biosensing in medical diagnoses and life sciences. For high-throughput and low-cost sensing, a high sensitivity is crucial for eliminating the pre-concentration process, while a simple setup of sensors is also desirable. This paper demonstrates a super-sensitivity for protein, which satisfies these requirements. The key device is a photonic crystal nanolaser, in particular with a nanoslot. Even using a simple setup, the nanolaser achieves an extraordinary-low detection limit for BSA protein, i.e. 255 fM on an average, which cannot be explained by its bulk index sensitivity. The specific adsorption of the protein is observed only around the nanoslot with strong laser intensity. This suggests that the super-sensitivity arises from the effective trapping of protein in the nanoslot.

Selective detection of sub-atto-molar Streptavidin in 10 13 -fold impure sample using photonic crystal nanolaser sensors

Biosensors selectively detecting a very small amount of biomarker protein in human blood are desired for early and reliable diagnoses of severe diseases. This paper reports the detection of protein (streptavidin: SA) in ultra-low concentration, with an ultra-high selectivity against contaminants, using photonic crystal nanolasers. For biotin-modified nanolasers in pure water with SA, an extremely-low detection limit of 16 zM is evaluated. Even in a mixture with 1 μM bovine serum albumin as the contaminant, 100 zM SA is detected, meaning a selectivity of 10(13). These are remarkable capabilities that are promising for practical biosensing in the medical applications mentioned above.

Photonic Crystal Point-Shift Nanolasers With and Without Nanoslots—Design, Fabrication, Lasing, and Sensing Characteristics

GaInAsP photonic crystal point-shift nanolasers operate at room temperature under pulsed and continuous-wave condition by photopumping with an effective threshold of ~1 μW, a single-mode peak of over 40 dB, and a small modal volume of ~0.2 times the cubic wavelength. We report the details of its design, fabrication process, measurement method, and lasing characteristics. In particular, we reveal that wide spectral broadening often observed for nanolasers under pulsed condition is caused by large thermal chirping. Then, we focus on a nanolaser-based liquid index sensor that is also applicable to detecting gases and biomolecules. The dependence of the lasers sensitivity and resolution on the modal profile and spectral linewidth are investigated. We also configure the laser in a large-scale array and demonstrate spectrometer-free sensor system. Finally, we present a nanoslot (NS) nanolaser that is particularly suitable for further reducing the modal volume and enhancing light-matter interaction and sensor performance. Additionally, we demonstrate the high sensitivity and spectral narrowing by the unique optical confinement in the NS.

Simultaneous detection of refractive index and surface charges in nanolaser biosensors

The emission intensity of a GaInAsP photonic crystal nanolaser is affected by the pH of the solution, in which the nanolaser is immersed. This phenomenon can be explained by the change in the redox potential, which modifies the filling of electrons at surface states of the semiconductor and hence the nonradiative surface recombination. This phenomenon allows the nanolaser to simultaneously and independently detect the refractive index and electric charges near the surface on the basis of the variation in emission wavelength and intensity, respectively. This paper demonstrates this function through alternate deposition of charged polyelectrolytes and hybridization of deoxyribonucleic acids.

Sensitive and selective detection of prostate-specific antigen using a photonic crystal nanolaser

The detection of low-concentration biomarkers is expected to facilitate the early diagnosis of severe diseases, including malignant tumors. Using photonic crystal nanolaser sensors, we detected prostate-specific antigen (PSA) from a concentration of 1 fM, which is difficult to detect by conventional enzyme-linked immunosorbent assay. The signal intensity and stability were improved by using a surfactant (i.e., ethanolamine). Even when a contaminant such as bovine serum albumin was mixed into the PSA sample, thereby increasing the concentration of the contaminant ten billion times, it was still possible to maintain a high level of detection.

Photonic crystal nanolaser sensors with ALD coating

Nanolaser sensors achieve ultrahigh sensitivity for biomolecules while unexpected noise was an issue. In this study, it was suppressed by ALD coating. Higher permittivity coating improved the sensitivity, suggesting unknown principles of this sensor.

Photonic crystal nanolasers with nanoslot structure for sensing applications

High-performance and low-cost sensors are critical devices for high-throughput analyses of bio-samples in medical diagnoses and life sciences. In this paper, we demonstrate photonic crystal nanolaser sensor, which detects the adsorption of biomolecules from the lasing wavelength shift. It is a promising device, which balances a high sensitivity, high resolution, small size, easy integration, simple setup and low cost. In particular with a nanoslot structure, it achieves a super-sensitivity in protein sensing whose detection limit is three orders of magnitude lower than that of standard surface-plasmon-resonance sensors. Our investigations indicate that the nanoslot acts as a protein condenser powered by the optical gradient force, which arises from the strong localization of laser mode in the nanoslot.

High sensitivity biosensing using nano-slot nanolaser

We have developed photonic crystal nanolaser and applied it to sensing liquids and bio-molecules. In this study, a nano-slot structure is introduced into the nanolaser, which strengthens the mode localization and improves the sensitivity, stability, and resolution as a sensor. As a result, a very low detection limit of 5.1 pg/ml has been achieved for BSA protein. It will be applicable to high-throughput label-free biosensing, while a mechanism of such low detection limit with the nano-slot is of great interest to investigate.

Label-free and spectral-analysis-free detection of neuropsychiatric disease biomarkers using an ion-sensitive GaInAsP nanolaser biosensor

The emission intensity of GaInAsP semiconductors that show an ion sensitivity is altered by the surface charge. In this study, we propose a biosensing technique using GaInAsP photonic crystal nanolasers based on this principle. Here, simple and rapid detection of collapsin response mediator protein 2 (CRMP2) is demonstrated, which is a promising biomarker candidate for neuropsychiatric diseases existing in peripheral white blood cells. We prepared CRMP2 as a standard protein and introduced sodium dodecyl sulfate (SDS) as an anionic surfactant to enhance the net negative charge of the protein. The nanolaser was modified in advance with an anti-CRMP2 antibody and then photopumped at a constant power. The laser emission intensity was monitored during the antibody-antigen reaction. Consequently, CRMP2 was detected as a decrease in the emission intensity. We achieved a lower limit for detection of 3.8 μg/mL that satisfies the requirement for clinical biomarker testing. Without the requirements of any kind of labels and spectral analyses, this technique allows for simple, rapid, and low-cost biomarker detection.

Sensitive and selective detection of prostate specific antigen beyond ELISA using photonic crystal nanolaser

We sensitively detected prostate specific antigen (PSA) using photonic crystal nanolaser sensors. In pure water and impure sample including 1 μM BSA, we detected <;100 fM PSA, which is lower than the limit of ELISA.