JPH05506098A - Electronic method to identify effective drugs to treat cancer patients - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Electronic method to identify effective drugs to treat cancer patients Background of the invention FIELD OF THE INVENTION This invention relates generally to anti-cancer drug therapy, and in particular to the most effective drugs to be administered to individual cancer patients. The present invention relates to a method for selecting a suitable anticancer drug.

When planning cancer chemotherapy for a particular cancer patient, doctors use a number of methods to choose an anticancer drug. This corresponds to drugs. The skill and experience of the examining physician will determine the ability to treat the patient's particular type of cancer. is a major factor in the selection of drug treatment regimens, but at the same time undesirable The effects of side effects must be minimized. Remove cancer tissue and send it to the laboratory A test by observing the effect of certain drugs on increasing the amount and number of cancer cells. is often done. Currently implemented methods are extremely time consuming and quantitatively It's also not accurate.

An electrical method of performing such a test is the Drags Exp port, C l1n, Ites, ■(5), pp. 641-674 (1986). ``Electrical impeder that instantly measures tumor cell sensitivity to anticancer drugs'' This method was proposed in a paper entitled ``A method for The method involves a suspension for cancer cells. A pair of tubes containing a liquid are each equipped with two electrodes that conduct an electric current through the suspension medium. There is. Cancer cells from the patient are injected into the medium of each tube. planned for use in patients The anti-cancer agent in question is placed in the medium of one tube, while the other tube serves as a reference.

A 10 kilohertz sinusoidal alternating current passes through each cell connected to the bridge array. Ru. The amount of difference in electrical impedance between two tubes after a certain amount of time is Showing the effect of drugs on cancer cells.

One overall objective of the present invention is to determine the amount or number of specific biological cells over time. The purpose of the present invention is to provide a method for estimating the effect of specific drugs on changes in .

One more specific object of this invention is to develop an optimal anti-cancer drug for use in the treatment of specific cancer patients. An object of the present invention is to provide an improved electronic method to aid in selecting agents.

Another object of the invention is to provide such a method with improved quantitative results and accuracy. It is to provide law.

Yet another object of the invention is to make such electrical measurements freely and quickly possible. The purpose of the present invention is to provide an electronic system that performs calculations from measured data.

Yet another object of the invention is to provide an easy method for monitoring changes in the amount or number of biological cells. The purpose is to provide equipment and various necessities for convenient use.

Summary of the invention The above and additional objects are achieved by the present invention.

Briefly and broadly speaking, this includes biological cells and the drug being tested. The conductivity (or its inverse function, the resistivity) of the medium that supports the lifespan of biological cells is Observed over time. The change in conductivity measured is due to the change in conductivity of the cells in the medium. Directly related to changes in quantity and number.

According to a more particular aspect of the invention, the effect of a particular drug on a patient's cancer cells is Determined before administering the drug to the patient. Observe only the changing conductivity. Only the effects of specific drugs on suppressing the increase in the amount and number of these cancer cells can be determined. Provides an accurate and quick way to determine Contains the same drug but does not contain any of the patient's cancer cells By comparing the impedance of the medium in another container as a reference , it is desirable to monitor this changing impedance. In a preferred embodiment, impedance of the medium without any significant effect from changing capacitance. very low voltages below 1000 Hz to measure the conductivity component of the An alternating current voltage is applied to the electrodes in each cell. Although DC voltage is preferable for this purpose, , which usually results in undesirable polarization effects or coating on the electrodes. , ultra-low frequency AC voltage is desirable.

The changing conductivity of the medium over time changes the amount or number of cells in the medium and It appears that the increase in both This is because the concentration of a substance is thought to be directly proportional to the cell concentration. Therefore, 2-3 o'clock The change in conductivity over a period of time or two days is the change in conductivity between cells in the medium over that time course. It directly shows the change in concentration of Direct connection between cell concentration and measurable ionic impurities relationship is that living cells maintain a constant electrochemical gradient across their boundaries. This seems to be a result of the fact that The electrochemical gradient is determined by the concentration gradient and each ion determined by the membrane potential of impurities. Electrochemical gradients are normal and distorted in cells. Different between cells.

That is, as the amount of a particular cell increases, it incorporates ions into the medium. and discharge, thereby exhibiting a measurable effect due to the conductivity of the medium.

According to another aspect of the invention, normal non-cancerous cells from the same patient are grown in the same type of medium. placed in a separate container with the body and the same anti-cancer drug added. normal cell media Any changing conductivity can be monitored at the same time as monitoring the changing conductivity of the cancer cell media. be seen. This allows doctors to monitor the planned anti-cancer drug on the patient's normal cells. effect can be obtained, that is, if that particular drug is given to the patient, Indicates the likely level of possible side effects. Therefore, doctors should Not only is it effective in inhibiting tumor growth, but it also affects the patient's normal, non-cancerous cells. Obtain sufficient information to select effective drugs with minimal destructive effects. can be done. The method of this invention allows for the administration of drugs to normal biological cells for other purposes. It also helps monitor effectiveness.

According to another aspect of the invention, the variation in electrical conductivity of a number of containers with the same medium is The effect of two or more drugs on both the patient's cancer cells and normal cells or two or more concentrations of the same drug, or both at the same time. be monitored as such. In a preferred embodiment, the conductivity reading is actually and simultaneously computer system and normalized results. The normalized results show the different effects on the patient's normal cells. cancer cells under the effects of different drugs and/or different drug concentrations. It is designed to show relative growth. Provide all of this information to the treating physician at once By doing so, thorough decisions can be made about the best drug to administer to the patient. It will be done.

Additional objects, advantages and features of the invention will be apparent from the following description of preferred embodiments thereof. However, the explanation will be given with reference to the attached figures.

Brief description of the drawing FIG. 1 generally illustrates an overall system for carrying out the various methods of the present invention. I will clarify.

Figures 2A and 2B are cross sections A-A and B-B showing the electrodes, respectively. Orthogonally oriented cross-sectional view of a single medium containing a cavity of the system of Figure 1 taken It is.

FIG. 3 specifically describes the details of the electronic circuitry of the system of FIG.

FIG. 4 illustrates specific data that collects the use of the example system of FIGS. 1-3.

Figure 5 shows a large number of (Figures 1-4) 2 is a flowchart specifically illustrating an example of the operation of the example system.

Figure 6 shows the data obtained by executing the means specifically shown in Figure 5. 2 is a flowchart specifically showing an example of calculations performed on data.

FIG. 7 specifically illustrates the form of the output of information resulting from the calculation step of FIG.

DESCRIPTION OF THE PREFERRED EMBODIMENT A preferred system for performing the various tests outlined above is primarily FIG. 3 will first be described. Standard commercially available plastic tissue The incubator 11 has an identical incubator, such as a recess 13 made therein and open to its top. It has multiple depressions in shape. The tray shown has 24 commonly used wells. of the same shape, but can of course be chosen to contain any convenient number of indentations. Wear. All or some desired number of indentations can be made using approximately the same amount of commercially available fines. Filled with cell maintenance medium 15. Indentations, as explained in more detail below. Some of these also contain chemicals within the media. Different concentrations of the same drug may or different chemicals may be placed in different recesses.

Biological cells are also included in some intracellular media. of the system described The purpose is to treat various drugs by both normal and cancerous cells of humans or other organisms. It is to determine a certain effect on the concentration of the product.

A standard commercially available plastic lid 17 may be used with the tray 11. There is also. The lid has a flat top with a downwardly projecting edge, and the top of the tray 11. always conforms to. To measure the conductivity of each recess in tray 11, a pair of electrodes It is equipped in a recess. The printed circuit board 19 physically supports these electrodes. attached to the top of the lid 17 to hold and provide electrical connection thereto. . A pair of electrodes 21 and 23 are arranged in depression 1 as illustrated in FIG. 2A. It is included in 3. A pin-shaped electrode with a small circular cross-section is preferred. In order to place the lid 17 on the tray 11, there is no physical obstruction when it is placed in the medium. This is because the amount is minimized. The electrode is made to span downwards and against the bottom of the tray. approach it, but avoid contact with it. Also pin-shaped electrodes , providing a fairly uniform current distribution between each pair in the medium in which they are immersed.

As best seen in Figures 2A and 2B, each electrode has a lid 17 and a printed It passes through both circuit boards 19.

Preferably, the electrodes are made of stainless steel. The pudding on the top of circuit board 19 The chopper circuit provides an individual conductor from each pin to the connection end 20 of the circuit board. . An example would be conductor trace 25 connecting to the tops of electrodes 21 and 23, respectively. and 27. Each conductive recessed pin has a connecting end 20 connected individually and a coupling socket. The connecting end 20 is inserted into the connector 29, and the electronic data acquisition circuit is connected via the conductor 31. It is connected to plate 39.

As shown in Figure 1, the tray 11, the lid 17, and the pudding attached to the lid 17 The circuit board 19 and the data collection board 39 are all connected to a commercially available incubator 30. placed inside. The temperature of the medium in the cavity of tray 11 is carefully controlled by the incubator. can be controlled. The ambient atmosphere is also controlled. one or more such basin structures The object is to monitor the effect in the medium of more depressions than can be obtained with just one tray. can be contained in the incubator at one time. Receives and processes low-level electrical signals The portion of the circuit that is This reduces measurement errors induced by heat. signal is higher After being amplified to a high level, they are then passed through conductor 32 to the outside core of the intensifier. connected to a computer system.

Computer 33 connects conductor 32 from data acquisition board 39 to any required interfaces. a signal is received through base logic 36 and conductor 34; Appropriate power supply source 3 8 and 40 include circuitry and optional logic 36 within the incubator. computer The controller 33 is marked with a dedicated card (circuit board) added to one of its expansion slots. It is desirable that it be made using a standard microcomputer system.

A standard computer system includes a standard peripheral input/output circuit board 37 and a A plurality of circuit boards 35 including an input/output (I10) circuit board 41 are included. structure Item 43 specifies the common system bus to which all such cards are connected. It is shown in

The computer system specifically shown for use with the present invention includes a monitor. the usual peripherals such as a computer 49, a keyboard 51 and some type of printer or A plotter 53 is included. These are connected to the appropriate cables 55, 57 and 55, respectively. and 59 to the peripheral input/output circuit board 37. computer system 33 is specifically shown in three parts in FIG. The first part 61 is mainly microprocessor 63, system random access memory 65, A basic computer consisting of a card 35 including a disk-controller 67 etc. system, all of which include the system bus 43 and other circuits (not shown). (not connected). Disk controller 67 is connected by circuit 69. is connected to a disk drive (not shown).

A second portion of the computer system 33 shown in FIG. A data collection plate 39 connected to an electrode placed in the medium in the recess of the tray 11. Ru.

For example, the indentation 13 in the basin 11 reduces thermally induced measurement errors, while other The electrode 23 is connected to ground potential. One electrode in each well in the incubator It is connected to a data collection board 39. Its function is interrogated in response to a signal from the control circuit 45. A voltage is applied to both ends of the electrode pair of each cell in the tray 11, which is connected. An analog signal proportional to the current flowing between the pair of electrodes is supplied to the circuit 47. Is Rukoto.

The third computer component is the measurement input/output circuit board 41, which may be any suitable circuit board. It is commercially available from several vendors. The circuit board 41 is connected to the microprocessor 63. in a controlled manner, energizing each pair of recessed electrodes one at a time, and then A digital signal is provided to a bus 43 that carries individual currents between the pole pairs. This data is Continuously captured by a computer system and stored on disk for later analysis - Appropriately stored in memory.

Data acquisition circuit board 39 includes a plurality of individual switches that It is like a switch 71 that controls the connection of the electrode for the recess 13, and each recess switches are monitored. One such switch is closed at a time. De Code circuit 73 detects a digital signal from circuit 45 specifying one switch. , then causes the control circuit 45 to close the switch while the digital signal remains.

An alternating current voltage source 81 is connected to a common node of all recess switches via a series resistor 79. Connected. Power supply 81 provides a voltage output that is programmable through bus 32. supply. The input of amplifier 83 is also connected to this common node of the recess switch. . A voltage source 81 is connected in series with the connected recess, thus creating a voltage divider, or Amplifier 83 measures the voltage drop across the connected recess.

The amplifier gain is also programmable via bus 45 and decode circuit 75. . The output of amplifier 83 is a sample and hold signal which is also controlled by signals on bus 32. It is added to the holding circuit 77. The signal on line 47 is connected to sample and hold circuit 77. From the output, it is passed through logic circuit 36 to the measurement input/output circuit board, where it is digitally Becomes tarred. Four separate circuits on data acquisition circuit board 39 are connected by bus 35. The bus is time-shared and controlled by the measurement input/output circuit board 41 and logic 3. 6 to each of these controlled circuits. desirable.

The system described with respect to Figures 1-3 to perform the tests outlined above. I will now explain the operation of the stem. A large number of depressions in the incubator 30 The specified number depends on the type and scope of the test to be performed. be done. The same amount of the same cell life support medium is placed in each active well. chosen The precise medium used must provide life support for the living biological cells under study and at least It is also placed in a medium with a slight depression. To the medium of at least some indentation also contains chemicals that are premixed with the medium prior to cell introduction. This causes cells to This is a drug whose effects are being studied.

Each test step by the system of Figures 1-3 lasts for at least a number of hours. However, it usually lasts a few days.

Before the start of such a test, the biological cells to be studied must be at least A few hours earlier, the plate was plated in the same medium used for the test without any chemicals. It is heard. This allows cells to live at a uniform temperature and in an atmosphere rich in carbon dioxide. It becomes possible to easily research the balance in the incubator 30. At the start of the test This initial equilibration medium is then removed using standard methods of blocking the cells. Leave them in separate, balanced depressions. The same medium then provides lifespan support to the cells under study. It is added to the depression to give it strength. These recesses should contain chemicals. The drug is premixed with the medium before being placed back into the well with the cells.

Standard, commercially available, 1ill woven culture tray of the type used with tray 11. is approximately 1.5 cm deep and approximately 1.5 cm in diameter. Contains an indentation of the same size of 2 cm.

Approximately 2 ml of medium is placed in each well. The number of cells placed in each well is It is also controlled by a standard method. For a given volume of medium the cells are too If there are too many, the result is cell deterioration. If the cell density is too low , also increases the proportion of noise in electrical measurements that are made once the voltage is applied. do. If the cell density is too small, there will be a delay in obtaining the current reading . At 2 mJ of medium, the workable range is 104-106 cells.

An example of a specific test procedure is the Dulhecco deformation of 2Φl. DMEM is used in each recess, which has a 10% fetal bovine serum, 200 units of penicillin and 200 nH strept Fortified with mycin. Each cell should contain approximately 10' human colon cells are located. The FU5 drug is available in three different amounts viz. 200 nanograms in the other cavity, 200 microprogram in the other cavity, and 200 nanograms in the other cavity. In the hollow, 2 milligrams are mixed with various hollow media. Ku The pot trays are maintained in an incubator in an atmosphere containing approximately 7% carbon dioxide. Next, cancer The effects of these drugs at various concentrations on inhibiting cell growth are discussed herein. as measured by the system described.

The voltage M81 is carefully chosen to have a low frequency, 10 A range extending below 000 hertz is satisfied. Frequency does not interfere with reading. is chosen to avoid the 60 Hz line frequency and its harmonics. It is also desirable. Frequencies of about 400 hertz have been used satisfactorily. This week The wavenumber range is the range in which any intrinsic capacitance has a very low impedance at low frequencies. low enough to be ineffective simply because it is extremely low. As discussed above, low Conductivity is not affected by capacitance so that a voltage source with a high frequency can be used. It is desirable to measure only But the frequency is affected by any polarization or electrode must be high enough to avoid coating. These effects are virtually negligible It is removed above 2-3 Hz.

The voltage applied by power supply 81 to each pair of electrodes is also carefully digitally controlled. It will be done. This voltage is generated by the biological cells under test that are placed in the medium voltage. This is typically about 90 millivolts. cell lifespan It is desirable to keep voltages as low as possible below that level without interfering with life. death However, if the voltage gets too low, the current level being measured will be proportionally lower. , which can reduce the signal-to-noise ratio below an acceptable limit. Approximately 1 The voltage applied across the cell electrodes of 0 millivolts accepts a wide range of applications. It turns out that it is possible. That voltage should match the desired signal-to-noise ratio as closely as possible. be made to do.

The voltage generated by the cell may also contribute to the current reading. certain model of cells with the same type of medium and cell concentration as the other wells. Although it is desirable to provide a dimple, no voltage is applied. to this reference medium One electrode is used to measure the voltage generated by the cell and in turn this The voltage is used to compensate for readings being taken on other cells.

Referring to Figure 4, a specific test example is illustrated, which includes the steps to run the test. Many aspects of the invention outlined above can be included using the system of Figures 1-3. It is. In this example, there are 60 individual indentations, each in groups of 4 indentations. Consists of. Media of the same type and capacity is placed in each of the 60 wells, but some has biological cells, and there are 15 different combinations corresponding to 15 groups of depressions, some of which are has one drug, another different drug, etc.

The four recesses in each group are identically constructed, and the four recesses of each type are inadvertent. Averages are taken to avoid any errors due to rational factors.

Of course, a different number of depressions can be added to each group, from one depression to more than 10 depressions. can be used.

Figure 4 is quite clear. As shown therein, the first group of four indentations 1 01 contains only the medium. This group does not include drugs or cells. This group 101-4 The average of the current readings in each depression is indicated by 11 and in the other depressions. used as a standard to compare current readings to.

A second group 103 of four depressions is inscribed to identify the best anti-cancer drug to administer to the patient. contains cancer cells from the patient on whom this test is performed. Each of the four depressions in group 103 The average of the current readings is denoted by I2, which is also used as a reference.

A third group of four wells 105 contains normal cells from the same patient in the medium. ing. Since normal cells are included in this test example, each drug's effect on the patient You can learn about the toxicity of The goal is to choose a drug and the concentration of that drug. This is desirable to suppress and stop any increase in the volume or number of cancer cells. while minimizing its negative impact on normal cell viability. these None of the wells in the first three groups contain any amount of the drug being tested.

In this example in Figure 4, two different types of chemicals are being tested, and each Two different concentrations. In each hollow group 107.109.111 and 113 includes one of four different drug and concentration combinations in this example. this These four groups are also used for reference purposes.

Of course, a larger number of different drugs or different concentration levels, and both Test simultaneously by easily expanding the number of indentations utilized Can be done.

East of the hollow 4 groups 115.117.119 and 121 are group 107.1 respectively 09.111 and 113, but in this case , each of which also contains cancer cells. Similarly, depressions 123.125.127 and 1 Group 29 contained the same drugs/concentrations as Groups 107, 109, 111 and 113, respectively. distribution, each containing the same number of normal cells in the patient.

The crude data for the current readings from each of the 60 dimples in the example of Figure 4 is the same as the operating current in Figure 5. Acquired by the system of Figures 1-3 as specifically illustrated by Figures 1-3. be done. Once that data is collected and stored on the computer system's hard drive, Once stored on disk, it is analyzed and processed according to the flowchart of FIG. Fifth The flowchart of FIG. 6 and FIG. 3 represents the operation of the system of FIG.

However, before describing the steps of FIGS. 5 and 6 in detail, let us explain the specific example of FIG. Typical results of the test will be discussed with respect to FIG. Curve 131 is Average current 1 divided by average current 2 (indentation group 103) during the strike time 1 (dent group 101).

Song, 41131, the size of untreated cancer cells on current readings with medium only and a proportional increase in number. Of course, the goal is to from the dimple group 109) to the current average I9 (the dimple group 117), as shown in curve 133. It is important to know the chemicals that close to a straight line and their concentrations. The curve 133 is Normalized by a depression with the same medium and drug concentration but no cells when the size and number of cancer cells in a medium containing a second concentration of a first drug over time Shows very slight changes.

The other curves in Figure 7 are compared to the untreated case specifically exemplified by Song [31] When combined with other drugs, the concentration slightly increases the size and number of cancer cells. To specifically illustrate the usual case of suppression, the result given by curve 133 is It is not as good as it could be with the combination of drugs given. Figure 1 - Figure 3 system Such output of the system allows for a good, easy determination of the most effective drugs and their concentrations. Provide readable information to the examining physician.

A similar type of output indicates the effect of the same drug and its concentration combination on normal cells of the same patient. It is generated to show the result.

In this case, the reference curve showing the effect of not having a -cut chemical is the average current II (reference standard). Figure 2 shows the change over time in the ratio of the indentation group 101) and I3 (indentation group 105). Positive The effects of various drugs on normal cells are shown in comparison by four other curves. be able to. One curve shows the average currents I4 (dip group 107) and 112 (<dip group). Figure 12 shows the change over time in the ratio of the group 123). The other curve is the average current I 5 (indentation group 109) and 113 (<indentation group 125), etc. during the test time. Shows barrel changes.

Referring to Figure 5, individual current readings can be obtained through the media in various recesses. The operation of the system shown in FIGS. 1-3 is specifically illustrated. this particular work The first step 141 in the process is to determine the number of depressions to be measured! 1<Start with a hole Ru. A large number of consecutive measurements, such as 50, of that one cell are each about 1 second apart. will be carried out.

These approximately 50 current measurements for one cavity are each obtained by the system and recorded as a single file in disk memory. obtained as directed by step 133. Data for one depression is obtained. 5, the process continues until it is the final cell, as indicated by step 135 in FIG. determine whether Otherwise, the processor, by step 137, Proceed to the next depression as indicated. The advance is to introduce a new pair of recessed electrodes into the system. to specify the different switches on circuit board 39 that should be closed to connect to the system. This is physically accomplished by changing the signal in circuit 145. Of course, Kubo Each switch on circuit board 39, such as switch 71 in FIG. (opens and closes intermittently to obtain a reading of the pores.

Once the measurement cycle has progressed to the next recess in sequence at step 137, the circuit board 39 Another of the switches is activated to produce different dimple current readings.

Once all the indentations have been measured in this manner, indicated by step 139. This will cause a delay in the measurements being taken.

This delay spaces the frequency of test cycles and one such cycle is hourly in this particular example. Of course, the frequency can be changed as appropriate. Can be done.

The measurement cycle specifically illustrated in FIG. - Resulting in a large number of data files accumulating on disk, with 50 such files The files are accumulated hourly in this example. Periodically, the raw data is analyzed and It is desirable to calculate the amount displayed using some suitable method as shown in Figure 7. . Figure 6 shows how large or small currents are desired to provide the information being processed. That happens once every hour or less frequently during the delay 139 in the cycle. A specific example of a data processing cycle is given below.

The first stage 141 of the processing cycle consists of one well given in one measurement cycle. Calculate the average of each of the 50 measurements made on each sample. The next step 143 is to It is to calculate the mean 11, I2.13, etc. from these averages for the group of .

Even after the raw data is replaced by these averages, a large amount of data remains It is recognized that In this example, such an average remains 15 per hour. typical tess can last for several days, and over such a long period of time the seventh There is no need to show graphs of the type shown. That is, as shown in step 145, A day suitable for a particular test in which all of the averages calculated in step 143 are performed. or for some other period of time, generally decreasing to the average of one set of each group of depressions. This is desirable.

The next step 147 is to calculate the type ratios shown in Figure 7 from these daily averages. It is to be. The final step 149 is to observe these ratios and the results of the test. hardware for readout on a monitor or through a printer whenever desired. The next step is to add these ratios to the graphical display file on the hard disk.

For some types of cancer, the number of drugs known to be potentially effective in treating them is increasing. has limitations. In these cases, the clinical researcher may be asked to A tray with media and various chemicals and a test of the type described with respect to FIG. It is most advantageous to provide a density of individual depressions that can be easily performed.

In this case, the cells are stretched in the same medium but for 2-3 hours before the start of the test. or placed in different containers for one day. Cells are then separated from their initial medium. are counted to place virtually the same number of cells in each (i.e., the fourth To carry out the test in the figure, the 60-well basin (or the number of each hollow was reduced) A large number of trays) are provided.

12 wells contain only the medium; the other 12 wells contain the first drug at the first concentration. and 12 additional depressions with a first drug at a second concentration and a second drug at a first concentration. 12 more wells, and finally a final one with a second drug at a second concentration. Contains 2 indentations. Of course, it may contain more drugs or different concentrations. Additional depressions can be provided if desired.

When treating harmful cells, the growth rate is close to zero or the sample is completely killed. Drug selection is helpful. In addition, if a drug or combination of drugs is However, if the drug or combination of drugs shows any adverse effects, additional testing may be necessary. indicated at higher dosages. This will help determine the correct dosage and correctness of the drug for your specific tumor. It is useful to determine both the new combination and the combination.

Quantitative indicators of cell growth rate are also used in clinical and laboratory research. test determines the normal cell growth rate, and it does not apply to any stimulation or inhibition of the cell growth rate. Measure the effectiveness of This is due to research on toxicity and the growth factors that affect cells. It is useful for research on the effects of biological response modification. It is also used for antibody research and of substances that enhance the growth rate of biologically engineered pressures of antibodies and drugs. This will help with development. The method is also used to monitor the health of cell lines.

While various aspects of the invention have been described in terms of preferred embodiments thereof, it will be appreciated that The invention is protected within the scope of the following claims.

Start data processing cycle summary Cancer cells in patients undergoing treatment are affected by cell life support along with the amount of anti-cancer drug used to treat the patient. will be added to the amount of media held. Cell conductivity suppresses increase in amount or number of cancer cells The drug is monitored over time to determine its effectiveness. to the patient's normal cells. data on the effectiveness of the same drug is collected at the same time, so the drug is This will reduce the effectiveness. The computer system handles multiple media containers simultaneously. be equipped to monitor at the time one or more drugs or drugs given; one or more concentrations of the product, or both, over a period of 2-3 hours or 2 days. can be decided at the same time.

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Claims (1)

[Claims] 1. A method for determining the effect of a specific anticancer drug on cancer patients, placing a large number of cancer cells from a patient into a quantity of cell life support medium containing an anti-cancer drug; and, Virtually any changing capacitance of the conductivity of the medium over time Any changes in the current can be monitored to determine if the change in current is the amount or number of cancer cells or The proportion of both changes is proportional to and the effect of anticancer drugs is shown by such changes. and a monitoring step. 2 The step of monitoring changes in medium conductivity involves passing a current through at least a portion of the amount of the medium. A method according to claim 1. 3 It is a method to determine the effect of anticancer drugs on cancer patients, and it involves collecting a large number of cancer cells from the patient. placing the cell in a cell life support medium containing an anti-cancer drug; positioning a pair of spaced apart pin-shaped electrodes in the medium; alternating ends of said pin pair of magnitude 90 millivolts at a frequency less than about 1000 hertz. Any change over time in the step of applying the voltage and in the current passing through the medium between the electrodes This is a step in which the current changes are proportional to the rate of cancer cell growth. and monitoring the effectiveness of the anti-cancer drug in inhibiting such growth. A method characterized by: 4. A method for determining the effect of a specific anticancer drug on cancer patients, The amount or number of cancer cells in the patient in the first amount of cell life support medium containing an anti-cancer agent. and monitoring the rate of change of both; The growth potential of the patient's non-cancerous cells in a second amount of cell life support medium containing an anti-cancer drug is and a step of monitoring the It determines the effect of a particular anticancer drug on a patient's normal cells and A method characterized in that the effect of the drug on cancer cells is determined together with the effect of the drug on cancer cells. 5 Monitoring changes in cancer cells includes monitoring the conductivity of the first volume of medium. and in which case the step of monitoring the growth potential of the non-cancerous cells includes a second amount of medium. 5. A method according to claim 4, characterized in that it includes the step of monitoring electrical conductivity. 6 It is a method to determine the effect of anticancer drugs on cancer patients, and the relationship between the patient's cancer cells and anticancer drugs is monitoring the conductivity magnitude of the amount of cellular life support medium containing both; Conductivity magnitude of different amounts of cell life support medium containing anticancer drugs in the absence of cut cells simultaneously monitoring the Compare any changes in conductivity and thereby determine which anti-cancer drugs will affect the patient's cancer cells. and a comparison step in which the effect of is determined. 7. A method for identifying effective anticancer drugs for use in treating cancer patients, the amount or number of cancer cells in a patient in a first amount of a cell life support medium comprising a first anti-cancer agent; or monitoring changes in both; the amount or number of cancer cells in the patient with a second amount of cell life support medium comprising a second anti-cancer agent; or a step of monitoring both changes simultaneously; Compare the monitored changes and thereby suppress the growth of the patient's cancer cells. and a comparison step in which the maximal effect of the second anticancer agent is determined. Method. 8. The amount of non-cancerous cells of the patient in the third amount of cell life support medium containing the first anticancer agent. or monitoring the rate of change in the number or both; growth of non-cancerous cells of a patient with a fourth amount of cell life support medium comprising said second anti-cancer agent; of the first and second anti-cancer drugs to the patient's normal cells. and a monitoring step in which the efficacy is determined and the effect of the drug on the cancer cells is determined. 8. A method according to claim 7, characterized in that: 9. The step of monitoring the change in the first volume of media includes monitoring the conductivity of the first volume of media. and monitoring the change in the second amount of the medium includes the step of monitoring the change in the second amount of the medium. According to claim 7, the step of monitoring the electrical conductivity of the amount of Method. 10 A method for determining the effect of anticancer drugs on cancer patients, in which each group has at least one A plurality of containers are set in at least two groups having containers, and the containers contain an anticancer drug therein. Set up a stage that retains an amount of cell life-supporting medium and removes a large number of cancer cells from the patient. the step of placing the medium in a first group of containers and not placing it in a second group of containers; floor and applying a voltage across the medium in the first and second groups of vessels and the flow therein; individually monitoring the magnitude of the composite current; A step of averaging the current flowing through the containers of the first group, and averaging the current flowing through the containers of the second group. and comparing the average current flow of the first and second groups of containers; The stage of monitoring any changes over time in the comparison, whereby changes are Directs the effectiveness of anticancer drugs to inhibit such growth in proportion to the rate of cancer cell growth and a monitoring step. 11. Setting up a third group of containers having at least one container therein; and retaining therein an amount of a life-supporting medium and an anti-cancer agent; placing a number of non-cancerous cells from a patient into the medium of a third group of containers; is not placed in the second group of containers; The step of applying voltage to both sides of the medium in the third group of containers and the resultant current flowing therethrough. separately monitoring the size; averaging the current flowing through the containers of the third group; and averaging the current flowing through the containers of the second and third groups; a step of comparing the flow of the flow; The stage of monitoring any changes over time in the comparison, whereby changes are and an additional monitoring step proportional to the effectiveness of the anticancer drug by replacement of the patient's normal cells. 11. The method of claim 10, comprising the steps of: 12 Set up third and fourth groups of containers with at least one container in each group the setting step, wherein the container holds an amount of cell life support medium therein; and placing a large number of cancer cells from the patient in the medium of the container of the third group, but in the fourth group The container media of the third and fourth groups are not placed in the container of the said container which does not receive the anti-cancer drug. floor and applying a voltage across the media in the third and fourth groups of containers and the amount of fluid flowing therethrough; separately monitoring the magnitude of the generated current; averaging the current flow in the third group of containers; and averaging the current flow in the third and fourth groups of containers; a step of comparing the flow of uniform current; The stage of monitoring all changes over time, so that changes are Proportional to the degree of unrestricted change in the amount and/or number of cancer cells in the recording medium 11. The method of claim 10, further comprising the step of monitoring. 13. Set up third, fourth and fifth container groups with at least one container in each group the container retains therein an amount of cell life-supporting medium and the anti-cancer the setting step without an agent; placing a number of cancer cells from a patient into the medium of a third group of containers; is not placed in the fifth group of containers; The step of placing a number of non-cancerous cells from the patient into the medium of the containers of the fourth group is the third and the step of not placing in a fifth group of containers; applying a voltage across the media in the third, fourth and fifth groups of containers; separately monitoring the magnitude of the composite current flowing through the A step of averaging the current flowing through the containers of the third group, and averaging the current flowing through the containers of the fourth group. a step of averaging the current flowing through the containers of the fifth group, and a step of averaging the current flowing through the containers of the third and fourth groups comparing the average current flowing through the container; The stage of monitoring any changes over time in the comparison, whereby changes are each without limitation on the amount and/or number of cancer cells in said medium. proportional to the degree of change and of the amount and/or number of normal cells in said medium. said monitoring step proportional to the degree of unrestricted change; 11. The method according to claim 10. 14 It is a method to determine the effectiveness of anticancer drugs given to cancer patients. also configuring a plurality of containers in at least two groups with one container. the setting step, wherein the container holds an amount of cell life support medium and an anti-cancer drug; placing a number of cancer cells from a patient into the medium of a first group of containers, and a second group of containers; the step of not placing the medium; The step is to place a large number of non-cancerous cells from the patient into the medium of the container of the second group, but not of the first group. placing said medium that is not placed in a container; applying a voltage to the medium in the containers of the first group and the second group and the composite voltage flowing therethrough; individually monitoring the magnitude of the flow; A step of averaging the current flow of the containers of the first group, and averaging the flow of the volume flow of the containers of the second group. and monitoring any changes in average current flow over time; Thereby, the change in the current flow in the containers of the first group is proportional to the change in cancer cells and directs the effect of the cancer drug, thereby causing changes in the flow of current in the second group of containers to The monitoring stage shows the effect of the anticancer drug on the patient's normal cells in proportion to the changes in the cells. A method characterized in that the method comprises: 15 A tray having a plurality of individual recesses within it, in which case at least one The first group of depressions contains a cell life support medium containing a first anti-cancer agent, and at least one The second group of depressions contains a cell life support medium containing a second anti-cancer agent and also contains at least The third group of depressions is a cell life supporter that has virtually no anticancer drugs in it. A tray characterized by containing a medium. 16. A lid adapted to be used with a tray with multiple recesses, a cover placed on the tray so as to cover the recess; , a printed circuit board attached to the top surface of the cover; a plurality attached to the printed circuit board at one end and extending through holes in the cover; pairs of electrically conductive pins, each pair being connected to a different one of at least a portion of the bays of said tray. The pins are placed across the plurality of holes so that the pins are in electrical contact with the medium within the recess. a number of pin pairs formed on the surface of the printed circuit board and extending from the pins to the circuit board; Multiple conductive traces that extend to the edge of the circuit board so that the pins and the trace electrically connected through the lid.