Advances in medical robots promise to improve modern medicine and the quality of life. Miniaturization of these robotic platforms has led to numerous applications that leverages precision medicine. ...In this review, the current trends of medical micro and nanorobotics for therapy, surgery, diagnosis, and medical imaging are discussed. The use of micro and nanorobots in precision medicine still faces technical, regulatory, and market challenges for their widespread use in clinical settings. Nevertheless, recent translations from proof of concept to in vivo studies demonstrate their potential toward precision medicine.
Miniaturization of medical robotic platforms has led to numerous applications that leverages precision medicine. In this review, the current trends of medical micro and nanorobotics for therapy, surgery, diagnosis, and medical imaging are discussed. Moreover, the technical, regulatory, and market challenges for their potential widespread use in clinical settings are addressed.
Cancer heterogeneity is regarded as the main reason for the failure of conventional cancer therapy. The ability to reconstruct intra- and interpatient heterogeneity in cancer models is crucial for ...understanding cancer biology as well as for developing personalized anti-cancer therapy. Cancer organoids represent an emerging approach for creating patient-derived in vitro cancer models that closely recapitulate the pathophysiological features of natural tumorigenesis and metastasis. Meanwhile, cancer organoids have recently been utilized in the discovery of personalized anti-cancer therapy and prognostic biomarkers. Further, the synergistic combination of cancer organoids with organ-on-a-chip and 3D bioprinting presents a new avenue in the development of more sophisticated and optimized model systems to recapitulate complex cancer-stroma or multiorgan metastasis. Here, we summarize the recent advances in cancer organoids from a perspective of the in vitro emulation of natural cancer evolution and the applications in personalized cancer theranostics. We also discuss the challenges and trends in reconstructing more comprehensive cancer models for basic and clinical cancer research.
Infectious diseases such as HIV-1/AIDS, tuberculosis (TB), hepatitis B (HBV), and malaria still exert a tremendous health burden on the developing world, requiring rapid, simple and inexpensive ...diagnostics for on-site diagnosis and treatment monitoring. However, traditional diagnostic methods such as nucleic acid tests (NATs) and enzyme linked immunosorbent assays (ELISA) cannot be readily implemented in point-of-care (POC) settings. Recently, plasmonic-based biosensors have emerged, offering an attractive solution to manage infectious diseases in the developing world since they can achieve rapid, real-time and label-free detection of various pathogenic biomarkers. Via the principle of plasmonic-based optical detection, a variety of biosensing technologies such as surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR), colorimetric plasmonic assays, and surface enhanced Raman spectroscopy (SERS) have emerged for early diagnosis of HIV-1, TB, HBV and malaria. Similarly, plasmonic-based colorimetric assays have also been developed with the capability of multiplexing and cellphone integration, which is well suited for POC testing in the developing world. Herein, we present a comprehensive review on recent advances in surface chemistry, substrate fabrication, and microfluidic integration for the development of plasmonic-based biosensors, aiming at rapid management of infectious diseases at the POC, and thus improving global health.
•Exosomes have been identified to hold exceptional value in clinical diagnostics and tumor therapy.•A short overview of conventional methods of exosome isolation is summarized.•The recent ...advancements of microfluidic strategy for exosomes isolation and detection are overviewed.•A brief overview of exosome-based drug delivery for tumor therapy is provided.•The current challenges and outlook of these fields are assessed.
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Exosomes are a class of cell-secreted, nano-sized extracellular vesicles with a bilayer membrane structure of 30–150 nm in diameter. Their discovery and application have brought breakthroughs in numerous areas, such as liquid biopsies, cancer biology, drug delivery, immunotherapy, tissue repair, and cardiovascular diseases. Isolation of exosomes is the first step in exosome-related research and its applications. Standard benchtop exosome separation and sensing techniques are tedious and challenging, as they require large sample volumes, multi-step operations that are complex and time-consuming, requiring cumbersome and expensive instruments. In contrast, microfluidic platforms have the potential to overcome some of these limitations, owing to their high-precision processing, ability to handle liquids at a microscale, and integrability with various functional units, such as mixers, actuators, reactors, separators, and sensors. These platforms can optimize the detection process on a single device, representing a robust and versatile technique for exosome separation and sensing to attain high purity and high recovery rates with a short processing time. Herein, we overview microfluidic strategies for exosome isolation based on their hydrodynamic properties, size filtration, acoustic fields, immunoaffinity, and dielectrophoretic properties. We focus especially on advances in label-free isolation of exosomes with active biological properties and intact morphological structures. Further, we introduce microfluidic techniques for the detection of exosomal proteins and RNAs with high sensitivity, high specificity, and low detection limits. We summarize the biomedical applications of exosome-mediated therapeutic delivery targeting cancer cells. To highlight the advantages of microfluidic platforms, conventional techniques are included for comparison. Future challenges and prospects of microfluidics towards exosome isolation applications are also discussed. Although the use of exosomes in clinical applications still faces biological, technical, regulatory, and market challenges, in the foreseeable future, recent developments in microfluidic technologies are expected to pave the way for tailoring exosome-related applications in precision medicine.
Untethered small actuators have various applications in multiple fields. However, existing small-scale actuators are very limited in their intractability with their surroundings, respond to only a ...single type of stimulus and are unable to achieve programmable structural changes under different stimuli. Here, we present a multiresponsive patternable actuator that can respond to humidity, temperature and light, via programmable structural changes. This capability is uniquely achieved by a fast and facile method that was used to fabricate a smart actuator with precise patterning on a graphene oxide film by hydrogel microstamping. The programmable actuator can mimic the claw of a hawk to grab a block, crawl like an inchworm, and twine around and grab the rachis of a flower based on their geometry. Similar to the large- and small-scale robots that are used to study locomotion mechanics, these small-scale actuators can be employed to study movement and biological and living organisms.
•Application of nanostructured substrates for isolation of circulating tumor cells (CTCs).•The fabrication methods for nanostructured surfaces are briefly discussed.•Underlying CTC capture mechanisms ...are described in detail.•We discussed major challenges faced by CTC isolation technologies.•Future directions are also discussed.
Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. CTCs hold the key to understanding the biology of metastasis and also play a vital role in cancer diagnosis, prognosis, disease monitoring, and personalized therapy. However, CTCs are rare in blood and hard to isolate. Additionally, the viability of CTCs can easily be compromised under high shear stress while releasing them from a surface. The heterogeneity of CTCs in biomarker expression makes their isolation quite challenging; the isolation efficiency and specificity of current approaches need to be improved. Nanostructured substrates have emerged as a promising biosensing platform since they provide better isolation sensitivity at the cost of specificity for CTC isolation. This review discusses major challenges faced by CTC isolation techniques and focuses on nanostructured substrates as a platform for CTC isolation.
The natural microenvironment of tumors is composed of extracellular matrix (ECM), blood vasculature, and supporting stromal cells. The physical characteristics of ECM as well as the cellular ...components play a vital role in controlling cancer cell proliferation, apoptosis, metabolism, and differentiation. To mimic the tumor microenvironment outside the human body for drug testing, two-dimensional (2-D) and murine tumor models are routinely used. Although these conventional approaches are employed in preclinical studies, they still present challenges. For example, murine tumor models are expensive and difficult to adopt for routine drug screening. On the other hand, 2-D in vitro models are simple to perform, but they do not recapitulate natural tumor microenvironment, because they do not capture important three-dimensional (3-D) cell–cell, cell–matrix signaling pathways, and multi-cellular heterogeneous components of the tumor microenvironment such as stromal and immune cells. The three-dimensional (3-D) in vitro tumor models aim to closely mimic cancer microenvironments and have emerged as an alternative to routinely used methods for drug screening. Herein, we review recent advances in 3-D tumor model generation and highlight directions for future applications in drug testing.
In nature, cells self‐assemble at the microscale into complex functional configurations. This mechanism is increasingly exploited to assemble biofidelic biological systems in vitro. However, precise ...coding of 3D multicellular living materials is challenging due to their architectural complexity and spatiotemporal heterogeneity. Therefore, there is an unmet need for an effective assembly method with deterministic control on the biomanufacturing of functional living systems, which can be used to model physiological and pathological behavior. Here, a universal system is presented for 3D assembly and coding of cells into complex living architectures. In this system, a gadolinium‐based nonionic paramagnetic agent is used in conjunction with magnetic fields to levitate and assemble cells. Thus, living materials are fabricated with controlled geometry and organization and imaged in situ in real time, preserving viability and functional properties. The developed method provides an innovative direction to monitor and guide the reconfigurability of living materials temporally and spatially in 3D, which can enable the study of transient biological mechanisms. This platform offers broad applications in numerous fields, such as 3D bioprinting and bottom‐up tissue engineering, as well as drug discovery, developmental biology, neuroscience, and cancer research.
3D assembly and coding of cells into heterogeneous living architectures based on magnetic levitation is presented. Living architectures are assembled and coded with controlled geometry and organization, preserving their functional properties. The developed system provides an innovative direction for monitoring and guiding the reconfigurability of living materials.
Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers ...(proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30-200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings.
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