Investing and non inverting amplifier applications of biotechnology
The rate at which the temperature of the cells changes is referred to as the scan rate and is specified by the user through the computer-interface A thermal effect measuring device 7 is connected to a sensor 8 that measures the difference in temperature between the two cells. Typical sensors include wire thermocouples or semiconducting thermocouples. The temperature differential is measured periodically as the cells are being heated during a scan. The temperature differential data is then sent from thermal effect measuring device 7 to computer 6, where it is saved along with the time of the measurement in the computer memory The cells 1 and 2 are surrounded by a thermal shield 9.
During adiabatic operation, the shield helps minimize heat exchange between the cells and their surroundings. The temperature of thermal shield 9 is monitored by an absolute temperature measuring device 13 which is activated by a sensor 14 typically a platinum resistance thermometer device or RTD which is mounted on the thermal shield.
Thermal shield 9 is connected to a heating and cooling device 10 typically an array of Peltier devices which is operated by a controller The signal to the controller 11 comes from the output of a summing amplifier 15 which receives two inputs. The first input 20 receives its signal from sensor 12 that monitors the difference between the temperature of thermal shield 9 and the average temperature of the two cells 1 and 2. The second input 16 receives its signal from a power source 17 whose output is controlled by computer 6.
The output from absolute temperature measuring device 13 is sent to computer 6 and used to determine the appropriate signal to send to power source 17 and subsequently onto the summing amplifier The absolute temperature information is repeatedly stored in the computer memory 30 in conjunction with the temperature differential between cells and the time of the measurement.
Additional cell heaters 18 and 19 are located on reference and sample cells 1 and 2, respectively. The power to each of these heaters is independently controlled directly by the output of computer 6. These cell heaters 18 and 19, which generate only small amounts of heat, are used to actively reduce any temperature differential between cells.
Through the computer interface 40, the user can select between passive compensation, in which additional heaters 18 and 19 are not used, or various levels typically low, medium, and high of active compensation, in which these additional heaters are used by computer 6 to actively minimize the temperature differential between cells 1 and 2. The choice of passive compensation or various levels of active compensation is equivalent to a selection between a number of instrument response times.
Improvement of Adiabatic Operation The calorimeter can operate in one of three modes: adiabatic, improved adiabatic, and non-adiabatic. Selection of a particular mode of operation is made through computer interface In the adiabatic mode, the second input 16 to the summing amplifier 15 is deactivated. As described previously, the first input 20 of the summing amplifier receives a signal from sensor 12 which monitors the difference between the temperature of thermal shield 9 and the average temperature of the two cells 1 and 2.
Based only on the temperature differential signal received at the first input 20, the summing amplifier 15 sends a signal to controller In turn, controller 11 regulates heating and cooling device 10 for thermal shield 9 in relation to the signal from summing amplifier 15, thereby minimizing the temperature difference between shield 9 and the cells 1 and 2.
In this way, the temperature of thermal shield 9 follows the temperature of the cells 1 and 2, which is controlled by computer 6 via power source 5 and cell heaters 3 and 4. However, the adiabatic mode of operation does not provide completely adiabatic performance.
For example, if cells 1 and 2 are raised to a temperature above room temperature and then cell heaters 3 and 4 are turned off, but the calorimeter remains in the adiabatic mode, the differential temperature between the shield and the cells will continue to be actively minimized as described above.
It is observed empirically, however, that the absolute temperature of the cells and shield will drift downward. If the calorimeter performed adiabatically, no drift in temperature would be observed. To improve adiabatic performance, the calorimeter can operate in the improved adiabatic mode. In this mode of operation, both inputs to summing amplifier 15 are activated. In addition to the signal received at the first input 20 from the differential temperature sensor 12, summing amplifier 15 receives a second signal at the second input 16 from computer 6 via power source This second signal represents a correction factor generated by an empirically-derived equation which is stored in computer memory The correction factor is a function of the current temperature of thermal shield 9 which is repeatedly measured and stored in computer memory 30 during operation.
The two signals received by summing amplifier 15, i. More generally, any summing circuit may be used which functionally combines the two input signals, whether by simple addition or by some other operation. The correction factor is repeatedly recomputed and revised as the cells are being heated during a scan or as they are being maintained at a particular temperature. The correction factor attempts to compensate for factors that limit adiabatic performance, such as heat exchange between the shield and the surroundings and temperature gradients within the calorimeter.
The calorimeter can also operate in a non-adiabatic mode. In this case, the cell heaters 3 and 4 are deactivated. The signal from computer 6 to the second input 16 of summing amplifier 15, via second power source 17, gives a specified rate of heating and cooling thermal shield as determined by a file specified by the user through computer interface 40 and stored in computer memory The file is a function of the temperature of thermal shield 9 which is measured repeatedly during the scan.
A signal is sent from summing amplifier 15 to controller 11 which in turn regulates heating and cooling device 10 accordingly. In this case, the temperature of the cells 1 and 2 follow the temperature of thermal shield 9 by heat conduction. Since the heat conduction process is relatively slow, the temperature of the cells typically lags behind the temperature of the thermal shield, in contrast to the former two cases where the temperature of the thermal shield is actively driven to follow the temperature of the cells.
Determination of Equation for Improved Adiabatic Operation The empirically-derived equation which gives the correction factor for improved adiabaticity is determined in a manner shown in FIG. A plurality of temperatures within a range of temperatures are selected. Cells 1 and 2 are filled with a standard liquid, typically water, and allowed to equilibrate thermally for a short time prior to the start of scanning step The lowest temperature is selected to begin the calibration run step The entire apparatus is brought to an initial temperature below the selected temperature by heating or cooling thermal shield 9 using the non-adiabatic mode of operation step Then a temperature upscan is started by supplying a given constant voltage from power supply 5 to cell heaters 3 and 4, which heats the cells at a nearly constant rate.
The upscan is initiated using the adiabatic mode of operation so the temperature of the thermal shield is made to follow the average temperature of the cells 1 and 2 step Once the temperature of thermal shield 9, which is monitored, reaches the selected temperature, the power to cell heaters 3 and 4 is shut off step The instrument still in the adiabatic mode, the difference between the temperature of thermal shield 9 and the average temperature of the two cells 1 and 2 is actively minimized.
The absolute temperature of thermal shield 9 is periodically measured and recorded step The temperature of the shield will tend to drift toward room temperature reflecting heat exchange from the cells to the surroundings via the shield. Using the temperature drift data collected in step and knowledge of the heat capacity of thermal shield 9 and cells 1 and 2, the rate of heat exchange between the calorimeter and the surroundings is then determined step Knowing the rate determined in step and the heating and cooling characteristics of device 10, enables one to then compute a correction which must be sent to controller 11 to compensate for the heat exchange between the calorimeter and the surroundings and eliminate the temperature drift.
This corrected voltage is sent to the second input 16 of summing amplifier 15 from computer 6 via power source 17 step The temperature of thermal shield 9 is again measured as a function of time. If it does not remain substantially constant, the signal to the second input 16 of summing amplifier 15 is iteratively modified from the initial result until the measured temperature of the shield remains substantially constant.
This final signal is recorded and stored in computer memory 30 along with the temperature step Steps are then repeated for each of the remaining temperatures selected in step step When calibrations are completed for all temperatures, the resulting data represents a correction factor as a function of temperature.
A temperature-dependent polynomial equation is fitted to the recorded data using standard non-linear least-squares regression techniques step Improving Constancy of Scan Rate During adiabatic or improved adiabatic modes of operation, the instrument produces improved constancy of scan rate. When power supply 5 provides a constant voltage to cell heaters 3 and 4, the temperature change in the cells 1 and 2 will initially rise linearly with time.
This initial scan rate is referred to as the nominal scan rate. As the temperature rises, however, the current scan rate will diverge from the nominal scan rate. These deviations arise due to various factors including for example temperature-dependent resistivity of cell heaters 3 and 4, the temperature-dependent heat capacity of cells 1 and 2 and their contents, and departures from adiabatic operation.
To produce a constant scan rate, computer 6 via the power source 5 sends a variable voltage to cell heaters 3 and 4 as determined by a second empirically-derived equation. This equation depends functionally on the desired scan rate, which is specified by the user prior to the scan through computer interface 40, and the temperature of thermal shield 9.
In other words, the voltage signal to cell heaters 3 and 4 is updated repeatedly based on the measured temperature of thermal shield 9. Equation for Improved Constancy of Scan Rate The second equation which provides improved constancy of scan rate is determined empirically using the method shown in FIG. The user selects a number of desired scan rates which span the range of scan rates that the user intends to employ. The selected scan rates are spaced close enough together that the correct voltage values can be interpolated for intermediate desired scan rates step The user then selects a temperature range which spans the temperature over which the instrument will be used.
To perform the calibration, cells 1 and 2 are first filled with a standard liquid. From the scan rates selected in step , a particular scan rate is selected step Using the non-adiabatic mode of operation, thermal shield 9 is cooled such that the temperatures of thermal shield 9 and cells 1 and 2 are at the lowest temperature in the temperature range selected in step step Using knowledge of the temperature-dependent resistance of cell heaters 3 and 4 and the heat capacity of cells 1 and 2 and their contents, the constant voltage required to produce the selected scan rate at the current temperature is determined step Then, the constant voltage determined in step is supplied to cell heaters 3 and 4 and the instrument is operated in the improved adiabatic mode step As the cells are being heated, the temperature of thermal shield 9 is measured as a function of time at intervals of, typically, five to one hundred seconds step Using the data from step , the actual scan rate as a function of temperature is computed.
By measuring the difference between actual scan rate and the nominal scan rate at each temperature, and by knowing the temperature-dependent resistance of cell heaters 3 and 4 and the heat capacity of cells 1 and 2 and their contents, a voltage correction can be computed for each temperature for which data was taken. The corrected voltage, when applied to the heaters, will produce a scan rate which more closely approaches the nominal scan rate step To further improve the voltage correction, the scan is repeated using the corrected voltages determined in step The voltage corrections are then iteratively modified until the desired rate of scan constancy is achieved.
The final voltage as a function of temperature is recorded and stored to computer memory 30 over the temperature range selected in step step A temperature-dependent polynomial equation is fit to the voltage V versus temperature T data from step using standard non-linear least-squares regression techniques. The equation is parametrized by the particular scan rate ri selected in step The equation is shown in 1 : V r.
The fit provides values for coefficients ai, bi, ci, di,. Steps are repeated for each scan rate selected in step step Once calibrations are completed for all scan rates, coefficients determined in step are grouped together according to the order of temperature to which they apply. From this data, the set of coefficients for a particular order of temperature can be fit to a polynomial equation in scan rate r using standard non-linear least-squares methods: EQU1 After this exercise is completed, the set of equations 2a , 2b ,.
The equation derived by the above method depends on the heat capacity of the test solution in the cells. Water is the most appropriate test solution for calibration, since most experiments are carried out using aqueous solutions. Experiments using non-aqueous solvents can be accommodated by repeating the method above with the appropriate test solution.
User-Selectable Response Time The instrument allows the user to select, through computer interface 40, among a number of instrument response times. The instrument response time characterizes the rate of thermal equilibration between reference cell 1 and sample cell 2.
A heat-producing event which occurs in one cell and not the other, will produce a temperature differential between cells. The temperature differential will dissipate over time as a result of thermal conduction between cells, i. The additional cell heaters 18 and 19 can be used to increase the rate of thermal equilibration between cells by heating cells differently in order to minimize the temperature differential between them, i. The different choices of response time for this instrument are typically in the range of three to thirty-five seconds.
Selection of the longest response time corresponds to passive compensation, in which the additional cell heaters 18 and 19 are not used. Shorter response times require active compensation and correspond to a particular gain setting in the computer. The computer multiplies the gain setting by the measured temperature differential between cells to determine the voltages used to differentially heat cell heaters 18 and During active compensation the instrument operates as follows.
Cell heaters 3 and 4, which are controlled by computer 6 via power source 5, initiate a scan by heating cells 1 and 2 at a specified rate. In addition, a small constant voltage is applied to cell heater 18 which is connected to reference cell 1. Because cell heater 18 provides a constant voltage to reference cell 1, sample cell 2 can be heated or cooled relative to reference cell 1 by adjusting the voltage to cell heater When a temperature in the cells is reached that triggers a heat producing event or possibly a heat absorbing event in sample cell 2, a temperature differential is measured by sensor 8 and transmitted to computer 6 via thermal effect analyzer 7.
Any loss in the connection between the skin and the patch es results in the under-dosing of the drugs to the patients and can cause morbidity. However, to the best of our knowledge, no arrangement was made by any existing literature to detect the loss of connection between the skin and the patches.
Another critical issue found in every drug delivery system was its ability to deliver only one drug at a time. The report says elderly people are the largest per capita consumer of drugs and are prescribed a higher number of medications [ 7 ]. In such patients, polypharmacy multiple drug use is mainly related to chronic diseases like cardiovascular diseases, diabetes, and memory-related diseases e. Polypharmacy is also found in low-income countries where disease like tuberculosis is among the most common chronic illness [ 7 ].
Hence, a single-channel system may not be sufficient, and the requirement of a multichannel iontophoretic drug delivery system becomes essential. Taking the cue from the above discussion, a smartphone-based remote-controlled iontophoretic drug delivery device has been developed in this study. Provisions have been made in the device to deliver multiple drugs. The program of the device can be regulated to tailor the duration of the drug delivery, and hence, the amount of the drug to be delivered into a patient as per the choice of the programmer.
Further, an in-built program to detect and alert the healthcare professionals or relatives on the detachment of the drug delivery patch es from the site of the application is also proposed. Materials and Methods Materials. Sorbitan monopalmitate was purchased from Loba Chemie Mumbai, India. Metronidazole was received as a gift from Aarti drugs, India. Development of the Signal Generator. In this study, a programmable signal generator was developed [ 8 ].
For the purpose, the Arduino Due microcontroller board was used. A look-up table two-dimensional array was used to generate a sinusoidal signal Appendix. The signal was generated using 60 points from the two-dimensional array. The sample index point was incremented until the 60 points within a fixed time of 1 ms.
This resulted in the generation of a sinusoidal signal having a frequency of 1 kHz and a peak-to-peak amplitude of 2. The signal generator was programmed to generate 2 independent analog signals, which were presented at the DAC0 and DAC1 terminals of the microcontroller board.
The signal generator was programmed to generate signals for a period of 2 h. Designing of the Iontophoretic Device. The circuit for the iontophoretic drug delivery system was developed as per the previously reported literature [ 9 ]. Some modifications were made in the circuits to suit our needs. The sinusoidal signal generator, which was developed using the Arduino Due, was used as the voltage signal generator.
The output signal from the high-pass filter was then used as the input for the operational amplifier OP-AMP based voltage buffer circuit. The output of the buffer was later converted into a current signal using a voltage-to-current converter. The arrangements were made so that the generated current was then injected through the iontophoresis cell. An LED-based visual indicator circuit was also incorporated to indicate the working status of the device.
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