A Route toward High-Detectivity and Low-Cost Short-Wave Infrared Photodetection: GeSn/Ge Multiple-Quantum-Well Photodetectors with a Dielectric Nanohole Array Metasurface.

High-detectivity and low-cost short-wave infrared photodetectors with complementary metal-oxide-semiconductor (CMOS) compatibility are attractive for various applications such as next-generation optical communication, LiDAR, and molecular sensing. Here, GeSn/Ge multiple-quantum-well (MQW) photodetectors with a dielectric nanohole array metasurface were proposed to realize high-detectivity and low-cost SWIR photodetection. The Ge nanohole array metasurface was utilized to enhance the light absorption in the GeSn/Ge MQW active layer. Compared with metallic nanostructures, the dielectric nanohole structure has the advantages of low intrinsic loss and CMOS compatibility. The introduction of metasurface architecture facilitates a 10.5 times enhanced responsivity of 0.232 A/W at 2 µm wavelength while slightly sacrificing the dark current density. Besides, the metasurface GeSn/Ge MQW photodetectors benefit 35% improvement in the 3 dB bandwidth compared to control GeSn/Ge MQW photodetectors, which can be attributed to the reduced RC delay. Due to the high responsivity and low dark current density, the room temperature specific detectivity at 2 µm is as high as 5.34 × 109 cm·Hz1/2/W, which is the highest among GeSn photodetectors and is better than commercial InSb and PbSe photodetectors operating at the similar wavelength. This work offers a promising approach for achieving low-cost and effective photodetection at 2 µm, contributing to the development of the 2 µm communication band.

Multicenter phase II trial of Camrelizumab combined with Apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer.

In the later-line setting or for patients with PD-L1-negative tumors, immunotherapy-based regimens remain ineffective against advanced triple-negative breast cancer (TNBC). In this multicentered phase II trial (NCT04303741), 46 patients with pretreated advanced TNBC were enrolled to receive camrelizumab 200 mg (day 1), and apatinib 250 mg daily, plus eribulin 1.4 mg/m2 (day 1 and 8) on a 21-day cycle until progression, or unacceptable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included toxicities, disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), and 1-year overall survival. With a median of 3 lines of prior chemotherapy in the advanced setting, 17.4% had received PD-1/PD-L1 blockade plus chemotherapy for advanced disease. The ORR was 37.0% (17/46, 95% CI 23.2-52.5). The DCR was 87.0% (40/46, 95% CI 73.7-95.1). Median PFS was 8.1 (95% CI 4.6-10.3) months. Tertiary lymphoid structure was associated with higher ORR. Patients with lower tumor PML or PLOD3 expression had favorable ORR and PFS. PD-L1 status was not associated with ORR/PFS. Grade 3/4 treatment-related adverse events occurred in 19 (41.3%) of 46 patients. Camrelizumab plus apatinib and eribulin shows promising efficacy with a measurable safety profile in patients with heavily pretreated advanced TNBC.

Strong Purcell effect in deep subwavelength coaxial cavity with GeSn active medium.

We propose a deep subwavelength plasmonic cavity based on a metal-coated coaxial structure with Ge0.9Sn0.1 as the active medium. A fundamental surface plasmon polariton mode is strongly confined on the sidewall of the metal core, with the quality factor up to 5×103 at 10 K. By reducing the cavity dimension to a few nanometers, this cavity mode shows a strong plasmon binding with the mode volume down to 8×10-10 (λ/n)3, and significant size-dependent damping caused by the non-local optical response. The Purcell factor is achieved as high as 2×109 at 10 K and 7×108 at 300 K. This cavity design provides a systematic guideline of scaling down the cavity size and enhancing the Purcell factor. Our theoretical demonstration and understanding of the subwavelength plasmonic cavity represent a significant step toward the large-scale integration of on-chip lasers with a low threshold.

Diversity of Dominant Peripheral T Cell Receptor Clone and Soluble Immune Checkpoint Proteins Associated With Clinical Outcomes Following Immune Checkpoint Inhibitor Treatment in Advanced Cancers.

Dynamic changes of the peripheral T cell receptor (TCR) and soluble receptors and ligands (sRLs) have the potential to be used as biomarkers to monitor the evolution of the immune system in tumor patients undergoing immunotherapy. These functional biomarkers could be used to predict immune response to treatment with immune checkpoint inhibitors (ICIs) and to provide high-value information on the immune function status of cancer patients, thereby helping physicians to make effective clinical decisions. We collected paired pre- and post-treatment peripheral blood samples from 31 solid tumor patients treated with ICIs. TCR and sRL status were investigated using next-generation sequencing and magnetic bead panels. We found that the diversity of the dominant TCR clone at baseline was correlated with durable clinical benefit in patients receiving single-agent treatment. The D50 index, the diversity from the cumulative 50% of the total complementary determinant region 3, was obtained during treatment. A significant difference in progression-free survival was demonstrated between the D50 high and D50 low groups. This result was validated in an independent cohort. A signature including soluble immune checkpoint proteins (sICPs) was identified. Upregulation of the signature during treatment was correlated with durable clinical benefit. All these results indicate that a novel biomarker based on peripheral TCR and sICPs has the potential to be used in prognostic prediction and for rapid determination of therapeutic outcomes in patients treated with immune checkpoint inhibitors.

Ge0.95Sn0.05 Gate-All-Around p-Channel Metal-Oxide-Semiconductor Field-Effect Transistors with Sub-3 nm Nanowire Width.

We demonstrate Ge0.95Sn0.05 p-channel gate-all-around field-effect transistors (p-GAAFETs) with sub-3 nm nanowire width (WNW) on a GeSn-on-insulator (GeSnOI) substrate using a top-down fabrication process. Thanks to the excellent gate control by employing an aggressively scaled nanowire structure, Ge0.95Sn0.05 p-GAAFETs exhibit a small subthreshold swing (SS) of 66 mV/decade, a decent on-current/off-current (ION/IOFF) ratio of ∼1.2 × 106, and a high-field effective hole mobility (µeff) of ∼115 cm2/(V s). In addition, we also investigate quantum confinement effects in extremely scaled GeSn nanowires, including threshold voltage (VTH) shift and IOFF reduction with continuous scaling of WNW under 10 nm. The phenomena observed from experimental results are substantiated by the calculation of GeSn bandgap and TCAD simulation of electrical characteristics of devices with sub-10 nm WNW. This study suggests Ge-based nanowire p-FETs with extremely scaled dimension hold promise to deliver good performance to enable further scaling for future technology nodes.

Photo detection and modulation from 1,550 to 2,000†nm realized by a GeSn/Ge multiple-quantum-well photodiode on a 300-mm Si substrate.

A GeSn/Ge multiple-quantum-well (MQW) p-i-n photodiode structure was proposed for simultaneously realizing high detectivity photo detection with low dark current and effective optical modulation based on the quantum confined Stark (QCSE) effect. The MQW stacks were grown on a 300-mm Ge-buffered Si substrate using reduced pressure chemical vapor deposition (RPCVD). GeSn/Ge MQW p-i-n photodiodes with varying mesa diameters were fabricated and characterized. An ultralow dark current density of 16.3 mA/cm2 at -1 V was achieved as expected due to the low threading dislocation density (TDD) in pseudomorphic GeSn layer. Owing to the ultralow dark current density and high responsivity of 0.307 A/W, a high specific detectivity of 1.37×1010 cm·Hz1/2/W was accomplished at 1,550 nm, which is comparable with commercial Ge and extended-InGaAs photodetectors. Meanwhile, the bias voltage-dependent photo response was investigated from 1,700 to 2,200 nm. The extracted effective absorption coefficient of GeSn/Ge MQW shows a QCSE behavior with electric field-dependent exciton peaks from 0.688 to 0.690 eV. An absorption ratio of 1.81 under -2 V was achieved at 2 µm, which shows early promise for effective optical modulation. The high frequency response was calculated theoretically, and the predicted 3-dB bandwidth for the photodiode with a mesa diameter of 30 µm could reach 12 GHz at -2 V.

High-efficiency GeSn/Ge multiple-quantum-well photodetectors with photon-trapping microstructures operating at 2 µm.

We introduced photon-trapping microstructures into GeSn-based photodetectors for the first time, and achieved high-efficiency photo detection at 2 µm with a responsivity of 0.11 A/W. The demonstration was realized by a GeSn/Ge multiple-quantum-well (MQW) p-i-n photodiode on a GeOI architecture. Compared with the non-photon-trapping counterparts, the patterning and etching of photon-trapping microstructure can be processed in the same step with mesa structure at no additional cost. A four-fold enhancement of photo response was achieved at 2 µm. Although the incorporation of photo-trapping microstructure degrades the dark current density which increases from 31.5 to 45.2 mA/cm2 at -1 V, it benefits an improved 3-dB bandwidth of 2.7 GHz at bias voltage at -5 V. The optical performance of GeSn/Ge MQW photon-trapping photodetector manifests its great potential as a candidate for efficient 2 µm communication. Additionally, the underlying GeOI platform enables its feasibility of monolithic integration with other photonic components such as waveguide, modulator and (de)multiplexer for optoelectronic integrated circuits (OEICs) operating at 2 µm.

Integrating GeSn photodiode on a 200 mm Ge-on-insulator photonics platform with Ge CMOS devices for advanced OEIC operating at 2 µm band.

High-performance GeSn multiple-quantum-well (MQW) photodiode is demonstrated on a 200 mm Ge-on-insulator (GeOI) photonics platform for the first time. Both GeSn MQW active layer stack and Ge layer (top Ge layer of GeOI after bonding) were grown using a single epitaxy step on a standard (001)-oriented Si substrate (donor wafer) using a reduced pressure chemical vapor deposition (RPCVD). Direct wafer bonding and layer transfer technique were then employed to transfer the GeSn MQW device layers and Ge layer to a 200 mm SiO2-terminated Si handle substrate. The surface illuminated GeSn MQW photodiode realized on this platform exhibits an ultra-low leakage current density of 25 mA/cm2 at room temperature and an enhanced photo sensitivity at 2 µm of 30 mA/W as compared to a GeSn MQW photodiode on Si at 2 µm. The underlying GeOI platform enables monolithic integration of a complete suite of photonics devices operating at 2 µm band, including GeOI strip waveguides, grating couplers, micro-ring modulators, Mach-Zehnder interferometer modulators, etc. In addition, Ge CMOS circuits can also be realized on this common platform using a "photonic-first and electronic-last" processing approach. In this work, as prototype demonstration, both Ge p- and n-channel fin field-effect transistors (FinFETs) were realized on GeOI simultaneously with decent static electrical characteristics. Subthreshold swings of 150 and 99 mV/decade at |VD| = 0.1 V and drive currents of 91 and 10.3 µA/µm at |VG-VTH| = 1 V and |VD| = 0.75 V were achieved for p- and n-FinFETs, respectively. This works illustrates the potential of integrating GeSn (as photo detection material) on GeOI platform for Ge-based optoelectronics integrated circuits (OEICs) targeting communication applications at 2 µm band.

High-speed photo detection at two-micron-wavelength: technology enablement by GeSn/Ge multiple-quantum-well photodiode on 300 mm Si substrate.

We report high-speed photo detection at two-micron-wavelength achieved by a GeSn/Ge multiple-quantum-well (MQW) p-i-n photodiode, exhibiting a 3-dB bandwidth (f3-dB) above 10 GHz for the first time. The epitaxy of device layer stacks was performed on a standard (001)-oriented 300 mm Si substrate by using reduced pressure chemical vapor deposition (RPCVD). The results showed promise for large-scale manufacturing. To our knowledge, this is also the first photodiodes-on-Si with direct radio-frequency (RF) measurement to quantitatively confirm high-speed functionality with tens of GHz f3-dB at 2 µm, which is considered as a promising candidate for the next data communication window. This work illustrates the potential for using GeSn to extend the utility of Si photonics in 2 µm band integrated optical transceivers for communication applications.

[Application of Static Characteristics of Plantar Pressure Distribution in the Assessment of Knee Joint Injury].

OBJECTIVE: This paper used plantar pressure analysis equipment to discuss the plantar pressure distribution pattern and balance ability of patients with the knee joint injury under static standing. METHODS: Zebris FDM-S plantar pressure analysis equipment was used to collect plantar pressure data from subjects with the knee joint injury and healthy control subjects. We compared the pressure values in each region of pelma, and then assessing the balance ability of the subjects based on the trajectory of the overall pressure center movement. RESULTS: Compared with the healthy control group, patients with knee joint injury have a significantly lower pressure in the heel areas and a significantly higher pressure in the middle foot area. And the total pressure of the injured limb foot in the patient group is lower than that in the contralateral foot. In addition, there is a significant increase in the parameters of the balance ability index in the patient group. CONCLUSIONS: The plantar pressure distribution pattern of patients with knee joint injury is different from that of normal people in static standing, and the balance ability is poor. Therefore, this method has a positive guiding significance in the evaluation and application of knee joint injury.

GeSn lateral p-i-n photodetector on insulating substrate.

We report the first experimental demonstration of germanium-tin (GeSn) lateral p-i-n photodetector on a novel GeSn-on-insulator (GeSnOI) substrate. The GeSnOI is formed by direct wafer bonding and layer transfer technique, which is promising for large-scale integration of nano-electronics and photonics devices. The fabricated GeSnOI photodetector shows well-behaved diode characteristics with high Ion/Ioff ratio of ~4 orders of magnitude (at ± 1 V) at room temperature. A cutoff detection beyond 2 µm with photo responsivity (Rop) of 0.016 A/W was achieved at the wavelength (λ) of 2004 nm.

Wireless amplified NMR detector for improved visibility of image contrast in heterogeneous lesions.

To demonstrate the capability of a wireless amplified NMR detector (WAND) to improve the visibility of lesion heterogeneity without the use of exogenous contrast agents, a cylindrically symmetric WAND was constructed to sensitively detect and simultaneously amplify MR signals emitted from adjacent tissues. Based on a two-leg high-pass birdcage coil design, this WAND could be activated by a pumping field aligned along the main field (B0 ), without perturbing MR signal reception. Compared with an equivalent pair of external detectors, the WAND could achieve more than 10-fold gain for immediately adjacent regions. Even for regions with 3.4 radius distance separation from the detector's cylindrical center, the WAND was at least 1.4 times more sensitive than an equivalent pair of surface arrays or at least twice as sensitive as a single-sided external surface detector. When the WAND was inserted into a rat's rectum to observe adjacent tumors implanted beneath the mucosa, it could enhance the detection sensitivity of lesion regions, and thus enlarge the observable signal difference between heterogeneous tissues and clearly identify lesion boundaries as continuous lines in the intensity gradient profile. Hyperintense regions observable by the WAND existed due to higher levels of blood supply, which was indicated by a similar pattern of signal enhancement after contrast agent administration. By better observing the endogenous signal contrast, the endoluminal WAND could characterize lesions without the use of exogenous contrast agents, and thus reduce contrast-induced toxicity.

High-performance GeSn photodetector and fin field-effect transistor (FinFET) on an advanced GeSn-on-insulator platform.

We report the first demonstration of high-performance GeSn metal-semiconductor-metal (MSM) photodetector and GeSn p-type fin field-effect transistor (pFinFET) on an advanced GeSn-on-insulator (GeSnOI) platform by complementary metal-oxide-semiconductor (CMOS) compatible processes. The detection range of GeSn photodetector is extended beyond 2 µm, with responsivities of 0.39 and 0.10 A/W at 1550 nm and 2003 nm, respectively. Through the insertion of an ultrathin Al2O3 Schottky-barrier-enhancement layer, the dark current IDark of the GeSn photodetector is suppressed by more than 2 orders of magnitude. An impressive IDark of ~65 nA was achieved at an operating voltage of 1.0 V. A frequency response measurement reveals the achievement of a 3-dB bandwidth of ~1.4 GHz at an illumination wavelength of 2 µm. GeSn pFinFET with fin width (Wfin) scaled down to 15 nm was also fabricated on the GeSnOI platform, exhibiting a small subthreshold swing (S) of 93 mV/decade, a high drive current of 176 µA/µm, and good control of short channel effects (SCEs). This work paves the way for realizing compact, low-cost, and multi-functional GeSn-on-insulator opto-electronic integrated circuits.

MiRNA extraction from cell-free biofluid using protein corona formed around carboxyl magnetic nanoparticles.

MicroRNA (miRNA) in urine has been considered as a potential biomarker for early-stage diagnosis of multiple diseases like urinary system cancer, kidney injury and diabetes, owing to their many demonstrated advantages including long-term stability and noninvasiveness. However, the traditional enrichment and extraction processes of miRNAs from urine are cumbersome and tedious due to the low concentration and multiple carriers of miRNAs. Herein, we present a novel method to collect low concentrations of miRNAs from dilute solutions such as urine and cell culture medium. 10-nm core sized magnetic nanoparticles with carboxylic acid coating can adsorb low-concentration proteins, and form protein corona which makes them easy to aggregate and precipitate for subsequent isolation. In urine and cell culture medium, these nanoparticles can aggregate with proteins, including miRNAs-associated protein Argonaute 2 and microvesicle-related proteins, to form precipitates, so that miRNAs can be easily extracted from pellets by small amount of lysis buffer for subsequent analysis such as real-time PCR. Our method provides a facile way to enrich miRNAs from biofluids without the need of ultracentrifugation and immunoprecipitations, bringing remarkable convenience to miRNAs-based biomarker research.

Two-micron-wavelength germanium-tin photodiodes with low dark current and gigahertz bandwidth.

We report the demonstration of a germanium-tin (Ge0.9Sn0.1) multiple-quantum-well p-i-n photodiode on silicon (Si) substrate for 2 µm-wavelength light detection. Characterization of the photodetector in both direct current (DC) and radio frequency (RF) regimes was performed. At the bias voltage of -1 V, a dark current density of 0.031 A/cm2 is realized at room-temperature, which is among the lowest reported values for Ge1-xSnx-on-Si p-i-n photodiodes. In addition, for the first time, a 3 dB bandwidth (f3dB) of around 1.2 GHz is achieved in Ge1-xSnx photodetectors operating at 2 µm. It is anticipated that further device optimization would extend the f3dB to above 10 GHz.

[Walking Ability Assessment System for Parkinson's Patients Based on Inertial Sensor].

In order to evaluate the ability of Parkinson's patients to walk comprehensively, a system based on MEMS to aid clinical quantification of ability in Parkinson's is established. The inertial units are respectively fixed on the back and the waist of subject to be measured. The Kalman fusion algorithm is used to extract the characteristic parameters of accelerometer and gyroscope data. SVM classifier is designed to train and test the classifier by the feature. The results show that the system possesses a high recognition rate for Parkinson's patients and normal subjects and for the classification of the walking ability of patients with Parkinson's disease. So, this system can aid doctors to give more object diagnostic conclusion.

[Digital System for the Geriatric Somatic Function Assessment].

At present, the somatic function assessment of the elderly mostly depends on the doctor's observation and the scale evaluation, and there isn't the objective and quantitative assessment criteria. In this paper, we design and construct a digital system for the geriatric somatic function assessment, which is based on digital ground, inertial unit, mobile terminal and PC terminal. The gait and balance parameters of the elderly were obtained by the Time Up and Go test and five postures test. Based on the linear regression model of gait and balance parameters, the system was used to evaluate the somatic function of the elderly. The experimental results show that the system not only can accurately distinguish elderly between fall and non-fall, but also has a high correlation between the score of the system and the score of clinical geriatric physical function scale.

[Development of Isokinetic Muscle Tone Testing System].

A new type of isokinetic muscle tone testing system was designed for the Parkinson's patients with dysmyotonia. The system consists of a mechanical device, a data acquisition unit, and a data processing and analyzing software. The mechanical device comprises an arm supporting device, a safety limiting device and a height adjusting device. Data acquisition unit, composed of a torque sensor module, a motor control module, a data communication module, and so on, is used to control the arm at constant speed and convert the sensor's analog signal into digital signal, then the signal is transmitted to the computer in real-time by USB interface. The data processing and analyzing software, developed by VC++, has finished the data processing, display, storage, generated the reports, et al. The experimental results show that this system is reliable and safe, not only can evaluate the degree of abnormal muscle tone in Parkinson's patients, but also can be used in the rehabilitation training of patients with dysmyotonia, which has strong expansibility.

[Quantitative Evaluation of Regularity of Finger Tapping Movement for Patients with Parkinson's disease].

Finger tapping test is a common testing item for patients with Parkinson's disease(PD)in clinical neurology.It mainly evaluates the fine motor function of patient's hand in three aspects:amplitude,speed and regularity of the movement.This paper focused on the quantitative assessment of regularity of finger tapping movement for PD patients.The movement signals of thumb and index finger were recorded by using inertial sensor unit in the process of tapping test.Two nonlinear dynamic indexes,approximate entropy(ApEn)and sample entropy(SampEn),were calculated,and then the values were statistically analyzed.The experimental results indicated that both indexes had significant differences between patient group and control group.Moreover,the indexes had relatively high correlation with the scores of corresponding unified Parkinson's disease rating scale(UPDRS)item rated by clinical clinician,which illustrated that these two indexes could reflect the injury level of the repetitive finger movement.So,as a reliable method,it can be provided to the clinical evaluation of hand movement function for PD patients.