A Highly Integrated Lab-on-a-CMOS Platform for Real-Time Monitoring of E. Coli Growth Kinetics.

Existing miniaturized and cost-effective solutions for bacterial growth monitoring usually require offline incubators with constant temperature to culture the bio-samples prior to measurement. Such a separated sample preparation and detection scheme requires extensive human intervention, risks contamination, and suffers from poor temporal resolution. To achieve integrated sample preparation and real-time bacterial growth monitoring, this article presents a lab-on-a-CMOS platform incorporates an optical sensor array, temperature sensor array, micro-heaters, and readout circuits. Escherichia coli's (E. coli) optimum growth temperature of 37 °C is achieved through a heat regulation system consisting of two micro-heaters and an on-chip temperature sensor array. A photodiode array with an in-pixel capacitive trans-impedance amplifier to reduce inter-pixel cross-coupling is designed to extract the optical information during bacterial growth. To balance the footprint, power consumption, and quantization speed, a 10 b column successive-approximation register (SAR)/single-slope (SS) dual-mode analog-to-digital converter (ADC) is designed to digitize the temperature and optical signals. Fabricated in a standard 0.18 um CMOS process, the proposed platform can regulate the sample temperature to 37 +/- 0.2/0.3 °C within 32 mins. Enabled by an on-chip heat regulation system and photodetectors, the prototype demonstrates a real-time monitoring of bacterial growth kinetics and antibiotic responses. Minute-level temporal resolution is achieved as this proposed platform is free of extensive and time-consuming human intervention. The proposed platform can be viably used in contamination sensitive applications such as antibiotic tests, stem cell cultures, and organ-on-chips.

An Optical and Temperature Assisted CMOS ISFET Sensor Array for Robust E. Coli Detection.

Both bacterial viability and concentration are significant metrics for bacterial detection. Existing miniaturized and cost-effective single-mode sensor, pH or optical, can only be skilled at detecting single information viability or concentration. This paper presents an inverter-based CMOS ion-sensitive-field-effect-transistor (ISFET) sensor array, featuring bacterial pH detection which is an indicator of viability. The proposed design realizes pH detection using the native passivation layer of CMOS process as a sensing layer and configuring an inverter-based front-end as a capacitive feedback amplifier. This sensor array is assisted by temperature sensing and optical detection which reveals bacterial concentration. The optical detection is enabled using the leakage current of a reset switch as a response to a light source. While in reset mode, the inverter-based amplifier works as a temperature sensor that could help to reduce temperature influences on pH and optical detection. All the functionalities are realized using one single inverter-based amplifier, resulting in a compact pixel structure and largely relaxed design complexity for the sensor system. Fabricated in 0.18 µm standard CMOS process, the proposed CMOS sensor array system achieves an amplified pH sensitivity of 221 mV/pH, an improved sensor resolution of 0.03 pH through systematic noise optimization, a linear optical response, and a maximum temperature error of 0.69 °C. The sensing capabilities of the proposed design are demonstrated through on-chip Escherichia coli (E. coli) detection. This study may be extended to a rapid and cost-effective platform that renders multiple information of bacterial samples.

A High Offset Distribution Tolerance High Resolution ISFET Array With Auto-Compensation for Long-Term Bacterial Metabolism Monitoring.

This paper presents a CMOS ion-sensitive-field-effect-transistor (ISFET) array with superior offset distribution tolerance, resolution and linearity for long-term bacterial metabolism monitoring. A floating gate ISFET is adopted as the sensing front end to maximize ion sensitivity and support ultra-long-term measurement. To solve the DC offset issue induced by trapped chargers and drifts in each ISFET sensor, a complementary readout scheme with column offset compensation is proposed. P-type and N-type source followers are combined to cover a wide range of input DC offsets while maintaining small area and high linearity. The DC offset is digitally compensated during signal readout to facilitate global amplification and quantization. Fabricated in 0.18 µm standard CMOS process, the ISFET array can tolerate an offset distribution beyond power supply with a linear pH-to-output response. Due to high ion sensitivity and low circuit noise, the whole system achieves a high resolution of 0.017 pH. The proposed ISFET system has successfully demonstrated an accurate pH monitoring of normal Escherichis coli growth for 11 hours and its response to antibiotics, showing long-term bacterial metabolism monitoring capability.

The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats.

To investigate the molecular mechanism of dihydrocapsaicin (DHC)-induced mild hypothermia in rats, and to compare its protective effect on the central nervous system with that of a conventional method of inducing hypothermia, 24 healthy male Sprague Dawley rats were randomly divided into four groups based on the following conditions: control group, cardiopulmonary resuscitation (CPR) group, body surface cooling group, and DHC group. Tracheal clipping was used to mimic asphyxia arrest. Rats were assessed for their neurological deficit scores. After sacrifice, immunohistochemical staining was used to examine caspase-3 expression in the cerebral cortex and TRPV1 (transient receptor potential vanilloid subfamily, member 1) expression in the hypothalamus. Terminal TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining was used to evaluate cell apoptosis in the cerebral cortex. Furthermore, intracellular Ca2+ concentration in the hypothalamus and arginine vasopressin (AVP) concentration in ventral septal tissues were also detected in these four groups. Results of our study showed that neurological deficit scores in the DHC group were significantly higher than those in the CPR and body surface cooling groups (p < 0.05). Caspase-3 expression in the cerebral cortex of control group rats was significantly lower than that in other three groups (p < 0.05). Hypothalamic TRPV1 expression, hypothalamic intracellular Ca2+ concentration, and AVP concentration in the ventral septum in the DHC group were significantly higher than that in the other three groups (p < 0.05). Within these three groups, there were significantly fewer apoptotic cells in the DHC and body surface cooling group rats than in the CPR group rats (p < 0.05). DHC has the neuroprotective effect. DHC induced mild hypothermia and reduces apoptosis through a mechanism whereby DHC activates TRPV1 on hypothalamic cells to cause a large Ca2+ influx, which alters corresponding physiological functions and causes the release of AVP to induce hypothermia.

[Combination of subradical external radiation and brachytherapy plus radical operation in the treatment of carcinoma of uterine cervix].

OBJECTIVE: To summarize retrospectively the 5-year survival rates and long-term complication of stage Ib-IIIa cervical carcinoma treated by combination of subradical external radiation and brachytherapy plus radical operation. METHODS: 106 patients with cervical carcinoma were all treated by radical hysterectomy and pelvic lymphadenectomy, of whom 78 had had preoperative radiotherapy (external radiation and brachytherapy), 16 combination of brachytherapy and radical operation, 12 adjuvant postoperative radiotherapy (external radiation and brachytherapy). (60)Co was used for external radiation, in which the point B dose was 25 - 30 Gy in preoperative radiation and 40 - 50 Gy in postoperative radiation. (192)Ir high-dose-rate afterloading unit was used in brachytherapy, with a dose of 6 - 18 Gy at point A. RESULTS: The follow up rate was 95.3%. The overall 5-year survival rates were 78.2% (61/78) in the preoperative radiotherapy group, 68.8% (11/16) in brachytherapy plus radical operation, 33.3% (4/12) in the postoperative radiotherapy group, showing a higher 5-year survival rate in the preoperative radiotherapy group than the postoperative radiotherapy group (P < 0.05). In stage II patients, the preoperative radiotherapy group -77.6% (45/58) also gave a higher survival than the postoperative radiotherapy group -25.0% (1/4) (P < 0.05). But all the other groups gave differences of insignificance. The chief long-term complications were radio-proctitis and cystitis, with incidences of 34.6% (27/78), 31.3% (5/16), 33.3% (4/12) in the preoperative radiotherapy group, brachytherapy plus radical operation group and the postoperative radiotherapy group (P > 0.05). CONCLUSION: The overall 5-year survival rate of combined subradical external radiation and brachytherapy plus radical operation was obviously higher than that of postoperative radiotherapy for stage Ib-IIIa and II patients, with statistically significant differences. However, the incidence of long-term complications give no statistical significance in the preoperative radiotherapy group or brachytherapy plus the operation group as compared with the postoperative radiotherapy group.