Circulating tumor cells (CTCs) have great potential to provide minimally invasive ways for the early detection of cancer metastasis and for the response monitoring of various cancer treatments. Despite the clinical importance and progress of CTC-based cancer diagnostics, most of the current methods of enriching CTCs are difficult to implement in general hospital settings due to complex and time-consuming protocols. Among existing technologies, size-based isolation methods provide antibody-independent, relatively simple, and high throughput protocols. However, the clogging issues and lower than desired recovery rates and purity are the key challenges. In this work, inspired by antifouling membranes with liquid-filled pores in nature, clog-free, highly sensitive (95.9 ± 3.1% recovery rate), selective (>2.5 log depletion of white blood cells), rapid (>3 mL/min), and label-free isolation of viable CTCs from whole blood without prior sample treatment is achieved using a stand-alone lab-on-a-disc system equipped with fluid-assisted separation technology (FAST). Numerical simulation and experiments show that this method provides uniform, clog-free, ultrafast cell enrichment with pressure drops much less than in conventional size-based filtration, at 1 kPa. We demonstrate the clinical utility of the point-of-care detection of CTCs with samples taken from 142 patients suffering from breast, stomach, or lung cancer.
Cellular membrane disruption induced by -amyloid (A) peptides has been considered one of the major pathological mechanisms for Alzheimer disease. Mechanistic studies of the membrane disruption process at a high-resolution level, on the other hand, are hindered by the co-existence of multiple possible pathways, even in simplified model systems such as the phospholipid liposome. Therefore, separation of these pathways is crucial to achieve an in-depth understanding of the A-induced membrane disruption process. This study, which utilized a combination of multiple biophysical techniques, shows that the peptide-to-lipid (P:L) molar ratio is an important factor that regulates the selection of dominant membrane disruption pathways in the presence of 40-residue A peptides in liposomes. Three distinct pathways (fibrillation with membrane content leakage, vesicle fusion, and lipid uptake through a temporarily stable ionic channel) become dominant in model liposome systems under specific conditions. These individual systems are characterized by both the initial states of A peptides and the P:L molar ratio. Our results demonstrated the possibility to generate simplified A-membrane model systems with a homogeneous membrane disruption pathway, which will benefit high-resolution mechanistic studies in the future. Fundamentally, the possibility of pathway selection controlled by P:L suggests that the driving forces for A aggregation and A-membrane interactions may be similar at the molecular level.
BackgroundEndoscopic technique is often applied for the diagnosis of diseases affecting internal organs and image-guidance of surgical procedures. Although the endoscope has become an indispensable tool in the clinic, its utility has been limited to medical offices or operating rooms because of the large size of its ancillary devices. In addition, the basic design and imaging capability of the system have remained relatively unchanged for decades.ObjectiveThe objective of this study was to develop a smartphone-based endoscope system capable of advanced endoscopic functionalities in a compact size and at an affordable cost and to demonstrate its feasibility of point-of-care through human subject imaging.MethodsWe developed and designed to set up a smartphone-based endoscope system, incorporating a portable light source, relay-lens, custom adapter, and homebuilt Android app. We attached three different types of existing rigid or flexible endoscopic probes to our system and captured the endoscopic images using the homebuilt app. Both smartphone-based endoscope system and commercialized clinical endoscope system were utilized to compare the imaging quality and performance. Connecting the head-mounted display (HMD) wirelessly, the smartphone-based endoscope system could superimpose an endoscopic image to real-world view.ResultsA total of 15 volunteers who were accepted into our study were captured using our smartphone-based endoscope system, as well as the commercialized clinical endoscope system. It was found that the imaging performance of our device had acceptable quality compared with that of the conventional endoscope system in the clinical setting. In addition, images captured from the HMD used in the smartphone-based endoscope system improved eye-hand coordination between the manipulating site and the smartphone screen, which in turn reduced spatial disorientation.ConclusionsThe performance of our endoscope system was evaluated against a commercial system in routine otolaryngology examinations. We also demonstrated and evaluated the feasibility of conducting endoscopic procedures through a custom HMD.
In this study, we demonstrate a novel platform for optical stimulation of neural circuits combined with a microfluidic culture method and microelectrode array measurements. Neuron-on-a-chip was designed and fabricated to isolate axons without a soma or dendrite. Thus, it is readily able to manipulate the neuronal alignment and to investigate the neuronal activity at the locations we want to observe. We adapted the optical stimulation technique to the arranged neurons to generate the neuronal signals in a non-invasive fashion. A blue light-emitting diode and a femtosecond laser with 780 nm center wavelength were used for neuronal activation and the corresponding neuronal signals were measured by MEAs at the same time. We found that one-photon light via caged glutamate provoked periodic spiking. In contrast, the femtosecond pulse irradiation generated repetitive firing at constant rates. Response times of one-photon and two-photon stimulation were around 200 ms and 50 ms, respectively. We also quantified neural responses, by varying optical parameters such as exposure time and irradiation power.
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