Highly sensitive, modification-free, and dynamic real-time stereo-optical immuno-sensor.

Modification-free biosensing with high specificity and sensitivity is essential for miniaturized, online, integrated, and rapid, or even real-time molecular analyses. However, most optical biosensors are based on surface pre-modification or fluorescent labeling, and have either low sensitivity or low quality factor (Q). To address these difficulties, in this study, an optical sensor prototype was developed with a microbubble optofluidic channel integrated inside a Fabry-Pérot cavity to three-dimensionally tailor the intra-cavity light field via the intra-cavity lensing (microbubble) configuration. A high Q-factor (∼105), small mode volume, and high light energy density were experimentally achieved with this "stereo-sensor" while maintaining an ultrahigh refractive index (RI) sensitivity (679 nm/RIU) and ultra-small RI resolution (∼10-7 RIU at 950 nm). Moreover, specific detection of very low concentration of biomolecules (5 fg/mL for human IgG and 0.5 pg/mL for human serum albumin (HSA)) and wide range of protein concentrations (e.g., fg/mL-ng/mL for human IgG and pg/mL-ng/mL for HSA) without probe pre-modification were achieved owing to the RI change specifically associated with the probe-target binding and the corresponding bio-macromolecular conformation change. This modification-free stereosensing scenario is applicable to continuous, real-time, and multiplexed operations, thus showing potential for online, integrated, dynamic, biomolecular analyses in vitro or in vivo, such as the dynamic metabolic analysis of single cells or organoids and point-of-care tests.

Ultrasensitive optofluidic coupled Fabry-Perot capillary sensors.

Refractive index (RI) measurements are pertinent in concentration and biomolecular detection. Accordingly, an ultrasensitive optofluidic coupled Fabry-Perot (FP) capillary sensor based on the Vernier effect for RI sensing is proposed. Square capillaries integrated with the coupled FP microcavity provide multiple microfluidic channels while reducing the complexity of the fabrication process. The incoherent light source and spectrometer used during measurement facilitate the development of a low-cost sensing system. An ultrahigh RI sensitivity of 51709.0 nm/RIU and detection limit of 2.84 × 10-5 RIU are experimentally demonstrated, indicating acceptable RI sensing performance. The proposed sensor has significant potential for practical and low-cost applications such as RI, concentration, or biomolecular sensing.

Label-free detection of cardiac troponin-I with packaged thin-walled microbubble resonators.

The measurement of cardiac troponin-I (cTnI) is widely used for diagnosing acute myocardial infarction (AMI) diseases because of its myocardial specificity. Packaged microbubble resonators with thin wall are utilized for label-free and specific detection of cTnI based on whispering gallery mode (WGM). This packaged structure can provide a good protection for the biosensor, improve the anti-interference ability of the sensor and reduce the system noise. The theoretical detection limit of the biosensors for cTnI in phosphate buffer saline (PBS) is 0.4 ag mL-1 (0.02 aM ). Furthermore, we demonstrated that the biosensors can be used to detect cTnI molecules in simulated serum and the theoretical detection limit is also 0.4 ag mL-1 (0.02 aM ). These results are much far below the clinical cut-off value and show a huge application potential for the detection of cardiac biomarkers of AMI.

Optical Whispering-Gallery-Mode Microbubble Sensors.

Whispering-gallery-mode (WGM) microbubble resonators are ideal optical sensors due to their high quality factor, small mode volume, high optical energy density, and geometry/design/structure (i.e., hollow microfluidic channels). When used in combination with microfluidic technologies, WGM microbubble resonators can be applied in chemical and biological sensing due to strong light-matter interactions. The detection of ultra-low concentrations over a large dynamic range is possible due to their high sensitivity, which has significance for environmental monitoring and applications in life-science. Furthermore, WGM microbubble resonators have also been widely used for physical sensing, such as to detect changes in temperature, stress, pressure, flow rate, magnetic field and ultrasound. In this article, we systematically review and summarize the sensing mechanisms, fabrication and packing methods, and various applications of optofluidic WGM microbubble resonators. The challenges of rapid production and practical applications of WGM microbubble resonators are also discussed.

Tunable optofluidic microbubble lens.

Optofluidic microlenses are one of the crucial components in many miniature lab-on-chip systems. However, many optofluidic microlenses are fabricated through complex micromachining and tuned by high-precision actuators. We propose a kind of tunable optofluidic microbubble lens that is made by the fuse-and-blow method with a fiber fusion splicer. The optical focusing properties of the microlens can be tuned by changing the refractive index of the liquid inside. The focal spot size is 2.8 µm and the focal length is 13.7 µm, which are better than those of other tunable optofluidic microlenses. The imaging capability of the optofluidic microbubble lens is demonstrated under a resolution test target and the imaging resolution can reach 1 µm. The results indicate that the optofluidic microbubble lens possesses good focusing properties and imaging capability for many applications, such as cell counting, optical trapping, spatial light coupling, beam shaping and imaging.

Hyperboloid-Drum Microdisk Laser Biosensors for Ultrasensitive Detection of Human IgG.

Whispering gallery mode (WGM) microresonators have been used as optical sensors in fundamental research and practical applications. The majority of WGM sensors are passive resonators that require complex systems, thereby limiting their practicality. Active resonators enable the remote excitation and collection of WGM-modulated fluorescence spectra, without requiring complex systems, and can be used as alternatives to passive microresonators. This paper demonstrates an active microresonator, which is a microdisk laser in a hyperboloid-drum (HD) shape. The HD microdisk lasers are a combination of a rhodamine B-doped photoresist and a silica microdisk. These HD microdisk lasers can be utilized for the detection of label-free biomolecules. The biomolecule concentration can be as low as 1 ag mL-1 , whereas the theoretical detection limit of the biosensor for human IgG in phosphate buffer saline is 9 ag mL-1 (0.06 aM ). Additionally, the biosensors are able to detect biomolecules in an artificial serum, with a theoretical detection limit of 9 ag mL-1 (0.06 aM ). These results are approximately four orders of magnitude more sensitive than those for the typical active WGM biosensors. The proposed HD microdisk laser biosensors show enormous detection potential for biomarkers in protein secretions or body fluids.

High-Q guided mode resonance sensors based on shallow sub-wavelength grating structures.

We present a systematic investigation on the enhancement of the quality (Q) factors for guided-mode resonance (GMR) sensors with shallow subwavelength grating structures. By introducing the coupled-mode model, a theoretical high-Q factor can be achieved by choosing the proper geometric structure. Based on this method, a GMR sensor with a Q factor up to 8000, which is an order of magnitude larger than those of typical GMR sensors with Q factors within 100 ∼ 300, was demonstrated experimentally. Besides, the approached GMR sensor achieved a bulk sensitivity of 135 nm RIU-1 with a high signal to noise ratio, which supports a detection limit of 1 ng ml-1 for bovine serum albumin detection. This high performance GMR sensor paves the way towards high-throughput industrial mass production, and shows great potential for other applications, such as optical filters, spectrometer, and bio-imaging.

Characterization of porcine cytokine inducible SH2-containing protein gene and its association with piglet diarrhea traits.

OBJECTIVE: The cytokine inducible SH2-containing protein (CISH), which might play a role in porcine intestine immune responses, was one of the promising candidate genes for piglet anti-disease traits. An experiment was conducted to characterize the porcine CISH (pCISH) gene and to evaluate its genetic effects on pig anti-disease breeding. METHODS: Both reverse transcription polymerase chain reaction (RT-PCR) and PCR were performed to obtain the sequence of pCISH gene. A pEGFP-C1-CISH vector was constructed and transfected into PK-15 cells to analysis the distribution of pCISH. The sequences of individuals were compared with each other to find the polymorphisms in pCISH gene. The association analysis was performed in Min pigs and Landrace pigs to evaluate the genetic effects on piglet diarrhea traits. RESULTS: In the present research, the coding sequence and genomic sequence of pCISH gene was obtained. Porcine CISH was mainly localized in cytoplasm. TaqI and HaeIII PCR restriction fragment length polymorphism (RFLP) assays were established to detect single nucleotide polymorphisms (SNPs); A-1575G in promoter region and A2497C in Intron1, respectively. Association studies indicated that SNP A-1575G was significantly associated with diarrhea index of Min piglets (p<0.05) and SNP A2497C was significantly associated with the diarrhea trait of both Min pig and Landrace piglets (p<0.05). CONCLUSION: This study suggested that the pCISH gene might be a novel candidate gene for pig anti-disease traits, and further studies are needed to confirm the results of this preliminary research.