Brain organoid-on-chip platforms have emerged as groundbreaking tools in neural disease modeling and drug discovery, offering a unique and highly accurate simulation of human organ physiology and function compared with traditional cell culture systems. This technology is a harmonious fusion of organ-on-a-chip and organoid culture technologies, leveraging their strengths to provide the most realistic in vitro replication of the in vivo environment, both physically and biologically. As both technologies continue to advance rapidly, this platform is highly promising in vitro platform for disease modeling. In this review, we summarize the historical developments, recent advancements, limitations, and future prospects of brain organoid-on-chip technology, aiming to illuminate the transformative potential of this platform in advancing our understanding and treatment of neural diseases.

The efficient immobilization of capture antibodies is crucial for timely pathogen detection during global pandemic outbreaks.Therefore,we proposed a silica-binding protein featuring core functional domains(cSP).It comprises a peptide with a silica-binding tag designed to adhere to silica surfaces and tandem protein G fragments(2C2)for effective antibody capture.This innovation facilitates precise site-directed immobilization of antibodies onto silica surfaces.We applied cSP to silica-coated optical fibers,creating a fiber-optic biolayer interferometer(FO-BLI)biosensor capable of monitoring the monkeypox virus(MPXV)protein A29L in spiked clinical samples to rapidly detect the MPXV.The cSP-based FO-BLI biosensor for MPXV demonstrated a limit of detection(LOD)of 0.62 ng/mL in buffer,comparable to the 0.52 ng/mL LOD achieved using a conventional streptavidin(SA)-based FO-BLI biosensor.Furthermore,it achieved LODs of 0.77 ng/mL in spiked serum and 0.80 ng/mL in spiked saliva,exhibiting no cross-reactivity with other viral antigens.The MPXV detection process was completed within 14 min.We further proposed a cSP-based multi-virus biosensor strategy capable of detecting various pandemic strains,such as MPXV,the latest coronavirus disease(COVID)variants,and influenza A protein,to extend its versatility.The proposed cSP-modified FO-BLI biosensor has a high potential for rapidly and accurately detecting MPXV antigens,making valuable contributions to epidemiological studies.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Waterborne viruses that can be harmful to human health pose significant challenges globally,affecting health care systems and the economy.Identifying these waterborne pathogens is essential for preventing diseases and protecting public health.However,handling complex samples such as human and waste-water can be challenging due to their dynamic and complex composition and the ultralow concentration of target analytes.This review presents a comprehensive overview of the latest breakthroughs in waterborne virus biosensors.It begins by highlighting several promising strategies that enhance the sensing performance of optical and electrochemical biosensors in human samples.These strategies include optimizing bioreceptor selection,transduction elements,signal amplification,and integrated sensing systems.Furthermore,the insights gained from biosensing waterborne viruses in human sam-ples are applied to improve biosensing in wastewater,with a particular focus on sampling and sample pretreatment due to the dispersion characteristics of waterborne viruses in wastewater.This review suggests that implementing a comprehensive system that integrates the entire waterborne virus detection process with high-accuracy analysis could enhance virus monitoring.These findings provide valuable insights for improving the effectiveness of waterborne virus detection,which could have sig-nificant implications for public health and environmental management.

Continuous drug monitoring is a promising alternative to current therapeutic drug monitoring strategies and has a strong potential to reshape our understanding of pharmacokinetic variability and to improve individualised therapy.This review highlights recent advances in biosensing technologies that support continuous drug monitoring in real time.We focus primarily on aptamer-based biosensors,wearable and implantable devices.Emphasis is given to the approaches employed in constructing biosensors.We pay attention to sensors'biocompatibility,calibration performance,long-term characteristics stability and measurement quality.Last,we discuss the current challenges and issues to be addressed in continuous drug monitoring to make it a promising,future tool for individualised therapy.The ongoing efforts are expected to result in fully integrated implantable drug biosensing technology.Thus,we may anticipate an era of advanced healthcare in which wearable and implantable biochips will automatically adjust drug dosing in response to patient health conditions,thus enabling the management of diseases and enhancing individualised therapy.