New treatment strategies are urgently needed for glioblastoma (GBM)-a tumor resistant to standard-of-care treatment with a high risk of recurrence and extremely poor prognosis. Based on their intrinsic tumor tropism, adoptively applied mesenchymal stem cells (MSCs) can be harnessed to deliver the theranostic sodium/iodide symporter (NIS) deep into the tumor microenvironment. Interleukin-6 (IL-6) is a multifunctional, highly expressed cytokine in the GBM microenvironment including recruited MSCs. MSCs engineered to drive NIS expression in response to IL-6 promoter activation offer the possibility of a new tumor-targeted gene therapy approach of GBM. Therefore, MSCs were stably transfected with an NIS-expressing plasmid controlled by the human IL-6 promoter (IL-6-NIS-MSCs) and systemically applied in mice carrying orthotopic GBM. Enhanced radiotracer uptake by 18F-Tetrafluoroborate-PET/magnetic resonance imaging (MRI) was detected in tumors after IL-6-NIS-MSC application as compared with mice that received wild-type MSCs. Ex vivo analysis of tumors and non-target organs showed tumor-specific NIS protein expression. Subsequent 131I therapy after IL-6-NIS-MSC application resulted in significantly delayed tumor growth assessed by MRI and improved median survival up to 60% of GBM-bearing mice as compared with controls. In conclusion, the application of MSC-mediated NIS gene therapy focusing on IL-6 biology-induced NIS transgene expression represents a promising approach for GBM treatment.
A proposed prototype of a 10-bit 1 MS/s single-ended asynchronous Successive Approximation Register (SAR) Analog-to-Digital Converter (ADC) with an on-chip bandgap reference voltage generator is fabricated with 130 nm technology. To optimize the power consumption, static, and dynamic performance, several techniques have been proposed. A dual-path bootstrap switch was proposed to increase the linearity sampling. The Voltage Common Mode (VCM)-based Capacitive Digital-to-Analog Converter (CDAC) switching technique was implemented for the CDAC part to alleviate the switching energy problem of the capacitive DAC. The proposed architecture of the two-stage dynamic latch comparator provides high speed and low power consumption. Moreover, to achieve faster bit conversion with an efficient time sequence, asynchronous SAR logic with an internally generated clock is implemented, which avoids the requirement of a high-frequency external clock, as all conversions are carried out in a single clock cycle. The proposed error amplifier-based bandgap reference voltage generator provides a stable reference voltage to the ADC for practical implementation. The measurement results of the proposed SAR ADC, including an on-chip bandgap reference voltage generator, show an Effective Number of Bits (ENOB) of 9.49 bits and Signal-to-Noise and Distortion Ratio (SNDR) of 58.88 dB with 1.2 V of power supply while operating with a sampling rate of 1 MS/s.
In this paper, a self-threshold voltage (Vth) compensated Radio Frequency to Direct Current (RF-DC) converter operating at 900 MHz and 2.4 GHz is proposed for RF energy harvesting applications. The threshold voltage of the rectifying devices is compensated by the bias voltage generated by the auxiliary transistors and output DC voltage. The auxiliary transistors compensate the threshold voltage (Vth) of the PMOS rectifying device while the threshold voltage (Vth) of the NMOS rectifying device is compensated by the output DC voltage. The proposed RF-DC converter was implemented in 180 nm Complementary Metal-Oxide Semiconductor (CMOS) technology. The experimental results show that the proposed design achieves better performance at both 900 MHz and 2.4 GHz frequencies in terms of PCE, output voltage, sensitivity, and effective area. The peak power conversion efficiency (PCE) of 38.5% at -12 dBm across a 1 MΩ load for 900 MHz frequency was achieved. Similarly, for 2.4 GHz frequency, the proposed circuit achieves a peak PCE of 26.5% at -6 dBm across a 1 MΩ load. The proposed RF-DC converter circuit shows a sensitivity of -20 dBm across a 1 MΩ load and produces a 1 V output DC voltage.
This paper presents an analog front-end for fine-dust detection systems with a 77-dB-wide dynamic range and a dual-mode ultra-low noise TIA with 142-dBΩ towards the maximum gain. The required high sensitivity of the analog signal conditioning path dictates having a high sensitivity at the front-end while the Input-Referred Noise (IRN) is kept low. Therefore, a TIA with a high sensitivity to detected current bio-signals is provided by a photodiode module. The analog front end is formed by the TIA, a DC-Offset Cancellation (DCOC) circuit, a Single-to-Differential Amplifier (SDA), and two Programmable Gain Amplifiers (PGAs). Gain adjustment is implemented by a coarse-gain-step using selective loads with four different gain values and fine-gain steps by 42 dB dynamic range during 16 fine steps. The settling time of the TIA is compensated using a capacitive compensation which is applied for the last stage. An off-state circuitry is proposed to avoid any off-current leakage. This TIA is designed in a 0.18 µm standard CMOS technology. Post-layout simulations show a high gain operation with a 67 dB dynamic range, input-referred noise, less than 600 fA/âHz in low frequencies, and less than 27 fA/âHz at 20 kHz, a minimum detectable current signal of 4 pA, and a 2.71 mW power consumption. After measuring the full path of the analog signal conditioning path, the experimental results of the fabricated chip show a maximum gain of 142 dB for the TIA. The Single-to-Differential Amplifier delivers a differential waveform with a unity gain. The PGA1 and PGA2 show a maximum gain of 6.7 dB and 6.3 dB, respectively. The full-path analog front-end shows a wide dynamic range of up to 77 dB in the measurement results.
A low power 12-bit, 20 MS/s asynchronously controlled successive approximation register (SAR) analog-to-digital converter (ADC) to be used in wireless access for vehicular environment (WAVE) intelligent transportation system (ITS) sensor based application is presented in this paper. To optimize the architecture with respect to power consumption and performance, several techniques are proposed. A switching method which employs the common mode charge recovery (CMCR) switching process is presented for capacitive digital-to-analog converter (CDAC) part to lower the switching energy. The switching technique proposed in our work consumes 56.3% less energy in comparison with conventional CMCR switching method. For high speed operation with low power consumption and to overcome the kick back issue in the comparator part, a mutated dynamic-latch comparator with cascode is implemented. In addition, to optimize the flexibility relating to the performance of logic part, an asynchronous topology is employed. The structure is fabricated in 65 nm CMOS process technology with an active area of 0.14 mm2. With a sampling frequency of 20 MS/s, the proposed architecture attains signal-to-noise distortion ratio (SNDR) of 65.44 dB at Nyquist frequency while consuming only 472.2 µW with 1 V power supply.
Recently, piezoresistive-type (PRT) pressure sensors have been gaining attention in variety of applications due to their simplicity, low cost, miniature size and ruggedness. The electrical behavior of a pressure sensor is highly dependent on the temperature gradient which seriously degrades its reliability and reduces measurement accuracy. In this paper, polynomial-based adaptive digital temperature compensation is presented for automotive piezoresistive pressure sensor applications. The non-linear temperature dependency of a pressure sensor is accurately compensated for by incorporating opposite characteristics of the pressure sensor as a function of temperature. The compensation polynomial is fully implemented in a digital system and a scaling technique is introduced to enhance its accuracy. The resource sharing technique is adopted for minimizing controller area and power consumption. The negative temperature coefficient (NTC) instead of proportional to absolute temperature (PTAT) or complementary to absolute temperature (CTAT) is used as the temperature-sensing element since it offers the best temperature characteristics for grade 0 ambient temperature operating range according to the automotive electronics council (AEC) test qualification ACE-Q100. The shared structure approach uses an existing analog signal conditioning path, composed of a programmable gain amplifier (PGA) and an analog-to-digital converter (ADC). For improving the accuracy over wide range of temperature, a high-resolution sigma-delta ADC is integrated. The measured temperature compensation accuracy is within ±0.068% with full scale when temperature varies from -40 °C to 150 °C according to ACE-Q100. It takes 37 µs to compute the temperature compensation with a clock frequency of 10 MHz. The proposed technique is integrated in an automotive pressure sensor signal conditioning chip using a 180 nm complementary metal-oxide-semiconductor (CMOS) process.
This paper presents a second-order discrete-time Sigma-Delta (SD) Analog-to-Digital Converter (ADC) with over 80 dB Signal to Noise Ratio (SNR), which is applied in a signal conditioning IC for automotive piezo-resistive pressure sensors. To reduce the flicker noise of the structure, choppers are used in every stage of the high gain amplifiers. Besides, to reduce the required area and power, only the CIC filter structure is adopted as a decimation filter. This filter has a configurable structure that can be applied to different data rates and input signal bandwidths. The proposed ADC was fabricated and measured in a 0.18-µm CMOS process. Due to the application of only a CIC filter, the total active area of the SD-ADC and reference generator is 0.49 mm² where the area of the decimation filter is only 0.075 mm². For the input signal bandwidth of 1.22 kHz, it achieved over 80 dB SNR in a 2.5 MHz sampling frequency while consuming 646 µW power.
