WO2018102393A1 - System for chemotherapy delivery and method of the same - Google Patents

Abstract

A system for chemotherapy delivery comprises a plurality of slots to receive a corresponding one of a plurality of cartridges; a plurality of pumps, wherein each of the plurality of pumps is configured to be connected to the corresponding one of the plurality of cartridges, and the plurality of pumps are configured to pump at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol; a blood glucose sensor communicatively coupled to the plurality of pumps, and configured to measure a blood glucose level of the patient; a processor connected to the plurality of pumps and the blood glucose sensor and configured to adjust a delivery property of the at least one drug according to the measured blood glucose level of the patient.

Description

System for Chemotherapy Delivery and Method of the Same Cross-Reference to Related Applications

[0001] This application claims the benefit of U.S. Provisional Application No.62/428,440, entitled "WARBURG EFFECT TARGETED CHEMOTHERAPY APPARATUS" filed November 30, 2016.

Technical Field

[0002] The application relates to Chemotherapy Apparatus, and more particular, to Warburg Effect targeted chemotherapy apparatus.

Background

[0003] Cancer is a disease of altered metabolism as much as it is a disease of uncontrolled cell growth. Targeting of metabolic pathways in cancer cells has a long history with many of the current chemotherapeutic drugs targeting a few of those pathways. In recent years, additional metabolic pathways have come of interest to target, namely cancer's reliance on glucose for energy. This altered metabolism in cancer is best utilized in PET scan technology, with sensitivity rates over 90%, making this altered metabolism nearly a universal trait of cancer.

Summary of the Invention

[0004] According to a first aspect of the disclosure, a system for chemotherapy delivery, comprising a plurality of slots, wherein each of the plurality of slots is configured to receive a corresponding one of a plurality of cartridges; a plurality of pumps, wherein each of the plurality of pumps is configured to be connected to the corresponding one of the plurality of cartridges, and the plurality of pumps are configured to pump at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol, wherein the at least one drug includes insulin, glucose and at least one chemotherapeutic drug, and the plurality of the cartridges are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively; a blood glucose sensor communicatively coupled to the plurality of pumps, and configured to measure a blood glucose level of the patient; a processor connected to the plurality of pumps and the blood glucose sensor and configured to adjust delivery property of the at least one drug according to the measured blood glucose level of the patient; and wherein the plurality of pumps are further configured by the processor to adjust pumping the at least one drug according to the adjusted delivery property.

[0005] According to another aspect of the disclosure, a method for chemotherapy delivery, comprising: receiving, by each of a plurality of slots, a corresponding one of a plurality of cartridges; pumping, by a plurality of pumps each connected to the corresponding one of the plurality of cartridges, at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol, wherein the at least one drug includes insulin, glucose and at least one chemotherapeutic drug, and the plurality of the cartridges are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively; measuring, by a blood glucose sensor communicatively coupled to the plurality of pumps, a blood glucose level of the patient; adjusting, by a processor connected to the plurality of pumps and the blood glucose sensor, delivery property of the at least one drug according to the measured blood glucose level of the patient; and adjusting, by the plurality of pumps, pumping the at least one drug according to the adjusted delivery property.

[0006] According to a third aspect of the disclosure, a computer readable storage medium, storing instructions when executed by a processor, cause the computer to perform operations comprising: controlling, a plurality of pumps each connected to a corresponding one of a plurality of cartridges to pump at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol, wherein the at least one drug includes insulin, glucose and at least one chemotherapeutic drug, and the plurality of the cartridges are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively; controlling a blood glucose sensor communicatively coupled to the plurality of pumps to measure a blood glucose level of the patient; adjusting delivery property of the at least one drug according to the measured blood glucose level of the patient; and controlling the plurality of pumps to adjust pumping the at least one drug according to the adjusted delivery property.

Brief Description of the Drawings [0007] Non-limiting and non-exhaustive embodiments of the present invention are described with reference to the following figures, wherein like reference numerals refer to like parts throughout the various views unless otherwise specified.

[0008] FIG. 1 is a schematic diagram illustrating comparisons of conventional

chemotherapy treatment versus Warburg Effect Target Chemotherapy on cancer

stem cells, according to the embodiments described herein.

[0009] FIG. 2 is a diagram illustrating pharmacokinetics of hypoglycemic glucose clamp metabolic targeted chemotherapy protocol according to an embodiment of the invention.

[0010] FIG. 3 is a diagram for a glucose clamp procedure done on mice with flank tumors.

[0011] FIG. 4 is results from two different glucose clamp plus chemotherapy procedures performed on mice with different tumor types derived from different human cancer cell lines.

[0012] Fig. 5 is a diagram for a system for chemotherapy delivery according to an embodiment of the invention.

[0013] FIG. 6 is a block diagram illustrating a system for chemotherapy delivery according to an embodiment of the invention.

[0014] FIG. 7 is a block diagram for a system for chemotherapy delivery according to another embodiment of the invention.

[0015] FIG. 8 is a system logic diagram for chemotherapy delivery according to an embodiment of the invention.

[0016] FIG. 9 is a high-level extent diagram showing an example of the architecture of the device for chemotherapy delivery according to an embodiment of the invention.

[0017] FIG. 10 is a flow diagram illustrating an example of method of chemotherapy delivery according to an embodiment of the invention.

[0018] FIG. 11 is a flow diagram illustrating an example of method of chemotherapy delivery according to another embodiment of the invention.

Detailed Embodiments

[0019] The embodiments set forth below represent the necessary information to enable those skilled in the art to practice the embodiments, and illustrate the best mode of practicing the embodiments. Upon reading the following description in light of the accompanying figures, those skilled in the art will understand the concepts of the disclosure and will recognize applications of these concepts that are not particularly addressed here. It should be understood that these concepts and applications fall within the scope of the disclosure and the accompanying claims.

[0020] The purpose of terminology used herein is only for describing embodiments and is not intended to limit the scope of the disclosure. Where context permits, words using the singular or plural form may also include the plural or singular form, respectively.

[0021] As used herein, unless specifically stated otherwise, terms such as "processing,"

"computing," "calculating," "determining," "displaying," "generating," or the like, refer to actions and processes of a computer or similar electronic computing device that manipulates and transforms data represented as physical (electronic) quantities within the computer's memory or registers into other data similarly represented as physical quantities within the computer's memory, registers, or other such storage medium, transmission, or display devices.

[0022] As used herein, terms such as "connected," "coupled," or the like, refer to any connection or coupling, either direct or indirect, between two or more elements. The coupling or connection between the elements can be physical, logical, or a combination thereof. References in this description to "an embodiment," "one embodiment," or the like, mean that the particular feature, function, structure or characteristic being described is included in at least one embodiment of the present disclosure. Occurrences of such phrases in this specification do not necessarily all refer to the same embodiment. On the other hand, the embodiments referred to also are not necessarily mutually exclusive.

[0023] As used herein, terms such as "cause" and variations thereof refer to either direct causation or indirect causation. For example, a computer system can "cause" an action by sending a message to a second computer system that commands, requests, or prompts the second computer system to perform the action. Any number of intermediary devices may examine and/or relay the message during this process. In this regard, a device can "cause" an action even though it may not be known to the device whether the action will ultimately be executed.

[0024] Note that in this description, any references to sending or transmitting a message, signal, etc. to another device (recipient device) means that the message is sent with the intention that its information content ultimately be delivered to the recipient device; hence, such references do not mean that the message must be sent directly to the recipient device. That is, unless stated otherwise, there can be one or more intermediary entities that receive and forward the message/signal, either "as is" or in modified form, prior to its delivery to the recipient device. This clarification also applies to any references herein to receiving a message/signal from another device; i.e., direct point-to-point communication is not required unless stated otherwise herein.

[0025] As used herein, unless specifically stated otherwise, the term "or" can encompass all possible combinations, except where infeasible. For example, if it is stated that data can include A or B, then, unless specifically stated otherwise or infeasible, the data can include A, or B, or A and B. As a second example, if it is stated that data can include A, B, or C, then, unless specifically stated otherwise or infeasible, the data can include A, or B, or C, or A and B, or A and C, or B and C, or A and B and C.

Localized Glucose Concentrations in Cancer Tissue

[0026] A recent study in Cancer Research looked at different metabolites in freshly frozen cancerous and normal tissues post-surgery. This study found glucose levels in cancerous tissues were 3 to 12 times less than healthy tissue. (Hirayama, et al., 2009) Due to the high glycolysis rate the cancer tissue is already depleted of glucose. This will of course be more pronounced in poorly vascularized ischemic tissue.

Glycolysis Effects on the Redox Status of Cellular Survival and Drug Resistance

[0027] Cancer cells often survive in an oxidative stressed environment. Many cancer drugs work through an increase in oxidative stress. Apoptosis requires an oxidative state within the cell to trigger and initiate the cascade that leads to cell death. Cancer cells are able to cope with the oxidative stress and avoid apoptosis through reduction via glutathione, the main cellular antioxidant. (Vaughn, et al., 2008) Oxidized glutathione is reconstituted via glutathione reductase using NADPH as an electron donor and producing NADP⁺ NADP⁺ is converted to NADPH in the pentose phosphate pathway, one of the two pathways which metabolize glucose. The other pathway, standard glycolysis, can be quickly shifted over to the pentose phosphate pathway upon the cell receiving oxidative stress, such as that delivered by drugs. (Patra, et al., 2014)

[0028] Cancer cells have a high capacity to metabolize glucose due to over expression of glucose transporters and metabolic enzymes. This high level of glycolysis leads to a buffering effect against oxidative stress via the recovery of oxidized glutathione. Many cancer drugs damage cancer cells through oxidative stress and high rates of glycolysis convey drug resistance to these drugs such as daunorubicin (Cao. Et al. 2007), adriamycin and paclitaxel (Maschek, et al., 2004), prednisolone (Ingrid et al., 2013), sorafenib (Tesori, 2015), and 5-fluorouracil (Shin, et al, 2009). Export of cisplatin by ABC transporters from cancer cells has been shown to be dependent on glutathione (Chen and Kuo, 2010).

Inhibition of Glycolysis

[0029] Inhibition of glycolysis is the core strategy to embodiments of the disclosure. Cancer cells which are unable to use glycolysis for energy generally become starved and rely on glutamine and autophagocytosis for energy. This can lead to cell necrosis. By limiting the level of blood glucose cancer cells quickly become depleted of their primary energy source. This will have many effects including the before mentioned necrosis and rate limited energy processes such as ATP -binding cassette transporters (ABC transporters). (Doyle, et al., 1998)

[0030] There are several investigational agents currently under study for glucose inhibition. One of these agents is 2-deoxyglucose (2DG) which shown effectiveness in the laboratory setting and has under gone clinical trials. 2DG being a glucose derivative is unable to be phosphorylated by hexokinase and can inhibit hexokinase activity. 2DG did however fail in the clinic. One of the main failure points was 2DG induced hyperglycemia. Cancer cells with elevated levels of Glucose transporter 1 (GLUT1 transporter) and hexokinase are able to survive in the enriched glucose environment despite the partial hexokinase inhibition. In addition, the 2DG can lead to irregular Electrocardiograph(ECG) heart rhythms. (Raez, et al., 2013).

[0031] One of a strategy of at least one embodiment for glycolysis inhibition is not to inhibit the common enzymes and glucose transporters, which are over expressed in cancer and requires enough inhibitor to completely disrupt and kill normal cells, but rather to inhibit glucose availability, which cancer cells require in larger quantities than normal cells to maintain their reductive state.

Warburg Effect Targeted Chemotherapy

[0032] Warburg effect targeted chemotherapy (WETC) uses insulin to induce hypoglycemia. Insulin does not interfere with any glycolysis enzymes. Insulin does however reduce overall blood glucose levels. Cancer tissue under normal blood glucose levels is already depleted of glucose which makes cancer tissue more sensitive to hypoglycemia. Additionally insulin induced hypoglycemia is a rapidly reversible process by giving intravenous glucose increasing the safety profile of this therapy.

[0033] FIG. 1 is a schematic diagram illustrating comparisons of conventional

chemotherapy treatment versus Warburg Effect Target Chemotherapy on cancer

stem cells, according to the embodiments described herein. Warburg effect targeted

chemotherapy, as shown in FIG. 1, is fundamentally different than conventional chemotherapy. Panel 1) (left part) of FIG.1 shows the conventional chemotherapy treatment, which features la) Under normal blood glucose levels cancer cells are fully feed through the use of glucose for energy resulting in the necessary ATP for drug resistance, lb) A high rate of glycolysis results in additional drug resistance and lc) this resistance protects the cancer cells DNA from DNA damaging drugs. Panel 2) (right part) of FIG.1 shows the Warburg Effect Target Chemotherapy, which features 2a) Under hypoglycemia cancer cells quickly deplete locally available glucose and enter in a metabolic crisis, resulting in lower ATP levels for normal cancer cell functions such as ABC transporters. 2b) A lower rate of glycolysis results in drug sensitivity. 2c)

Hyperglycemic cancer cells' DNA is unprotected from DNA damaging chemotherapy drugs resulting in increased cancer cell death.

Safety of Warburg Effect Targeted Chemotherapy - Xi'an, China

[0034] Cure Cancer Worldwide in conjunction with several hospitals in China have been treating patients using a combination of insulin induced hypoglycemia in combination with standard chemotherapy treatments, generally given multiple times in a 3 week window but at 10% the standard dose. The safety of these treatments has been evaluated as well as the side effects.

[0035] Insulin-Induced Hypoglycemia Safety Profile

Insulin Induces Retention of 5-Fluoro-Uricil in Cancer Cells [0036] 5-fluorourcil (5-FU) is a common drug used in chemotherapy and was developed in the 1950s. 5-FU is transported into cells via nucleoside transporters and is from there metabolized into several metabolites, some of which block RNA and DNA synthesis. One of the metabolites, 5-FdUMP, along with 5, 10-methylenetetrahydrofolate (5,10-CH2-TFIF), forms a complex with thymidylate synthase (TS) which inactivates TS's function. The inactivation of TS causes insufficient thymidine for DNA synthases and repair. This makes synthesis phase (S-phase) cells especially sensitive to 5-FU. 5,10-CH2-THF is a downstream metabolite of folate, who's intracellular concentration is increased by insulin via decrease activity of the folate export mechanism. Levofolinic acid (leucovorin) is often given in conjunction with 5-FU to provide the folate precursor for 5, 10-CH2-THF production necessary for 5-FU's inhibitory complex with thymidylate synthase.

[0037] A published study in 2007 (Zou et. al. Acta pharmacologica sinica 28.5 (2007): 721-730.) showed pretreatment with insulin several hours before addition of 5-FU resulted in greater inhibition of cell growth and higher percentage of apoptotic cell populations when compared to cells treated with 5-FU but without insulin treatment. They also showed an increase in the percent of S-phase cells with treatment of insulin. They claimed enhanced uptake of 5-FU by cells treated with insulin but did so indirectly. 5-FU concentrations in cell culture media was decreased when cells were treated with insulin and there was an increase in the 5-FdUMP/5,10- CH2-THF/TS complex. They attributed these observations to increased uptake but did not make the link between increase metabolism of folate and incorporation into the TS complex.

[0038] While the pentose phosphate pathway is the main source of NADPH in most cancer cells, folate metabolism can also produce NADPH from NADP⁺. Inhibition of the folate pathway, such as the use of 5-FU, along with hypoglycemia induced glucose deprivation, adds a combinatorial effect by furthering reducing available glutathione.

Pharmacokinetics of Warburg Effect Targeted Chemotherapy

[0039] Precise timing is necessary when combining anti-cancer drugs and hypoglycemia. The drugs need to be at their peak pharmacological effectiveness during the "Hypoglycemic

Therapeutic Window", see FIG. 2. FIG. 2 is a diagram illustrating pharmacokinetics of hypoglycemic glucose clamp metabolic targeted chemotherapy protocol according to an embodiment of the invention. As shown in FIG. 2, drugs can be given before, during or after induction of hypoglycemia dependent upon their pharmacological profile so their corresponding peak correlates with that of the hypoglycemic therapeutic window.

Glucose Clamp as a Means to Induce Hypoglycemia

[0040] The glucose clamps technique was first developed in 1979 and is a means of delivering insulin and glucose intravenously to precisely control blood glucose levels. This technique is used in the field of diabetes to diagnose and develop new drugs for diabetes. It has been used safely to induce hyperglycemia and hypoglycemia as it provides a finely controlled way to induce changes in blood glucose levels. Hypoglycemia has been shown to be safe at 3.0 mmol/L for up to two hours although with altered ECG readings. (Laitinen, et al., 2008)

Preclinical Animal Trials Utilizing Glucose Clamps to Create the Hypoglycemic

Therapeutic Window

[0041] The glucose clamp technique has been well developed in animals models for the purpose diabetes research. (Ayala, et al., 2011) We have adapted this technique for use in a SCID mouse xenograft model. FIG. 3 gives a schematic of this procedure. Briefly, mice are injected subcutaneously in the hind flank with a standard amount of cancer cells sufficient to cause a tumor to grow. After a few weeks when tumor volume measures around 300-500mm3, mice undergo jugular vein cannulation. Mice are fasted for 5 hours prior to treatment with

chemotherapy drugs. Depending on the pharmacokinetics of the drug, drugs are either given before the start of the glucose clamp or during the clamp procedure to correspond to the maximum effectiveness of the drug during the "hypoglycemia therapeutic window". Injection pumps containing insulin, glucose and washed erythrocytes from donor mouse blood are connected to a swivel mixer which is in turn connected to the jugular catheters. For the initiation of the hypoglycemic clump, a bolus injection of insulin is given to reduce initial blood glucose levels which typically take around 30 minutes to lower blood glucose. Then a steady state of insulin and glucose is given to maintain blood glucose levels between 30-50 mg/dL for two hours. In practice, blood glucose levels range from 22-51 mg/dl with an average around 34 mg/dL (1.9 mmol/L). FIG. 4 shows results from two tests with different cancer cells and drugs. A549 cells are of human lung cancer origin and mice bearing A549 tumors were administered two treatments, 2 days apart, of pemetrexed, given IV. before start of the clamp, 10 mg/kg, gemcitabine, given IV. at the start of hypoglycemia, and cisplatin, given IV. at the start of hypoglycemia, 0.5mg/kg. HCT-116 cells are of colon cancer origin and mice bearing HCT-116 tumors were administered two treatments, 2 days apart, of 5-fluorouricil, given IV. before start of clamp, 10 mg/kg, irinotecan, given IV. at the start of hypoglycemia, 10 mg/kg, and cisplatin, given IV. at the start of hypoglycemia, 0.5mg/kg.

Warburg Effect Targeted Chemotherapy Delivery System

[0042] The apparatus is a machine which regulates blood glucose levels, monitors ECG rhythms and delivers chemotherapy drug treatment intravenously via a pump system. The apparatus is able to regulate blood glucose levels over a longer duration of time than a simple inject once method. While the apparatus lowers blood sugar levels to a hypoglycemic state, chemotherapy is delivered to the patient though several pumps located inside the apparatus. The chemotherapy drug is contained in proprietary cartridges designed to fit in only the chemotherapy pumps located inside the apparatus while insulin and glucose each have their own proprietary cartridges making improper loading of the machine impossible (i.e. the insulin cartridge will not physically fit into the pump for glucose or chemotherapy drug and vice versa). As this system is a direct pump feed, the apparatus also includes a magnetic mixer for diluting insulin, glucose and chemo drugs into saline (saline also delivered by pump in proprietary cartridge).

[0043] While the apparatus controls blood glucose levels and delivers chemotherapy drugs, it also has many safety features. The main safety concern with hypoglycemia is abnormal heart rhythms. While long duration (about 2 hours) of hypoglycemia with the use of a glucose clamp is generally safe in healthy individuals, we are treating cancer patients with various co-morbidities and extra care is needed. An integrated ECG monitor is included which is able to trigger the glucose pump to elevate blood sugar levels in the case of an irregular heartbeat and/or reduce or cease administration of insulin. An external manually controlled glucose syringe is also available which can be operated by medical personnel. For proper medication delivery, the apparatus includes a bar code reader (or RFID chip or other identifying mechanism) which properly identifies chemotherapy drug cartridges so medical personnel can correctly load the machine with the drug the patient is to receive and lights a LED over the correct pump camber for the corresponding drug. Further, the apparatus can use the identifying mechanism to confirm that cartridges are not being reused or are counterfeit by connecting to a central database via a wired or wireless connection and verifying the identified cartridge is valid and/or hasn't been used before.

[0044] The apparatus has integrated software that receives instrument feeds from the continuous blood glucose monitor and the ECG monitor and interprets those feeds for display and for pump actions such as addition of glucose due to blood glucose levels dropping below the target range. The software package can be preprogrammed to deliver precise doses of drug by controlling the pump piston movement and through the bar code reader can insure the proper chemotherapy drug is loaded as per the preprogrammed treatment protocol. The apparatus can suggest a protocol based on cancer type and other variables and/or accept a protocol via wired or wireless connection. If an accepted protocol varies from a suggested protocol, the apparatus can issue a warning, which may be overridden by medical personnel.

Chemotherapy Treatment under Hypoglycemia

[0045] The apparatus lowers blood glucose levels with insulin and then administers a reduced level of chemotherapy drugs. These treatments are repeated frequently, several times a week, to achieve a clinical response. Long duration of hypoglycemia, up to 2 hours, during chemotherapy treatment is necessary as the half-life activity of many chemotherapy drugs are in this range. A standard treatment would be first to lower blood glucose levels by half of normal levels by injecting insulin intravenously. Then, while hypoglycemia is induced, chemotherapy drugs are delivered over a period of time, in minutes up to several hours. Hypoglycemia is maintained during the treatment time by injecting additional insulin or glucose to regulate blood sugar levels. ECG heart rhythms are monitored during this time to prevent any adverse cardiac events by injection of glucose to bring blood glucose levels back to normal in the case of an adverse cardiac event.

Mechanical features of the WETC Delivery System:

• Continuous blood glucose monitoring system able to regularly relay (potentially up to the minute or real time) blood glucose levels.

• Insulin/glucose pump regulatory system able to maintain predetermined blood glucose levels.

• Multiple pump system able to deliver not only insulin and glucose but also several

chemotherapy drugs. • Internal magnetic mixer which can mix insulin, glucose and/or chemotherapy drugs with saline to deliver a constant fluid flow into the patient even when the protocol calls for a slower flow rate of drug. The mixer is able to dilute out chemotherapy drugs into saline which may otherwise be at higher than desired concentration to deliver intravenously.

• Uses wired or wireless technology to interface with blood glucose and/or ECG monitor.

• Contains USB, firewire, wired Ethernet, wireless Ethernet, serial port and other computer interfacing ports to update firmware and download and upload patient data and verify cartridges.

Safety features of the WETC Delivery System:

• ECG monitoring system able to alert the system to any adverse cardiac events and return patient to normal blood glucose levels.

• A secondary calibration blood glucose monitor is integrated into the machine which tests fresh patient blood from lancets, intravenous (i.v.) or port draws to insure the continuous blood glucose monitor is properly reading blood glucose levels.

• External glucose delivery syringe for manual glucose delivery.

• Bar code reader and LED light system to insure correct drug is placed in the correct pump slot.

• Unique fitting shaped cartridges which only fit into the correct pump chamber for insulin, glucose and drugs pumps.

• Large display screen for easy to see read outs of current blood glucose levels and ECG status even across the room.

• A pressure sensor will indicate a clogged port or i.v. line and turn off the machine pumps to prevent over pressure of the lines and veins.

• Anti-reflux valve is placed in line with the main input line tube and inhibits back flow from the patient into the machine.

• An in-line air detector prevents air embolisms from occurring by detecting and removing air from the main line into a waste container.

• A system heater controls condensation build up which can occur if cold cartridges of insulin, glucose or drugs (typically stored cold) are placed into the device before acclamation to room temperature. Software features of the WETC Delivery System

• Software is programmable with patient information and their treatment protocol.

• Software is able to store patient information and treatments given in local and remote databases.

• Pump loading protocol interprets bar code labels on drug cartridges and lights an LED light so medical personnel correctly loads different pumps with the correct drug cartridge.

• Software controls a display panel and speaker for visual and audio output.

• Software reads monitor feeds from blood glucose and ECG monitors and interprets those feeds to pump out insulin or glucose to maintain proper blood sugar level.

• Software is able handle adverse events such as irregular heartbeat and take appropriate action such as glucose injection and alerting medical personnel.

• Software is able to control pumps to deliver a precise dose of chemotherapy drug over a variable amount to time by controlling the flow rate of the pump and overall volume delivered.

• Software controls saline pump flow rate to send both drugs and saline to the mixer for proper drug dilutions.

• Software has protocol for flushing/cleaning the system and clearing air from tubing.

• Human interface with push buttons or touch pad display technology.

• Uses password, swipe card and/or finger print recognition so only medical personnel can access machine functions.

[0046] FIG. 5 is diagram for a system 300 for chemotherapy delivery according to an

embodiment of the invention. The system 300 comprises a plurality of cartridges 310, 312, 314, 316 and 318 for insulin, glucose, chemotherapy drugs and/or other drugs, and/or saline, a plurality of pumps (not shown in FIG. 5) configured to receive the plurality of cartridges 310, 312, 314, 316 and 318, a blood glucose sensor 320, a mixer 350, a display 330 which can include a GUI, an ECG monitor system 340 with ECG leads, a processor (not shown in FIG. 5) that is communicatively coupled to the other components which will be discussed in further details with respect to FIG. 6 and FIG. 7. [0047] FIG. 6 is a block diagram illustrating a system 400 for chemotherapy delivery according to an embodiment of the invention. Referring to FIG. 6, the system 400 for chemotherapy delivery comprises a plurality of slots 410, wherein each of the plurality of slots 410 is configured to receive a corresponding one of a plurality of cartridges 420; a plurality of pumps 430, wherein each of the plurality of pumps 430 is configured to be connected to the

corresponding one of the plurality of cartridges, and the plurality of pumps 430 are configured to pump at least one drug contained in at least one of the plurality of cartridges 420 to a patient according to a treatment protocol. The at least one drug includes insulin, glucose and at least one chemotherapeutic drug, and the plurality of the cartridges 420 are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively. The system 400 further comprises a blood glucose sensor 440 communicatively coupled to the plurality of pumps 430, and configured to measure a blood glucose level of the patient; and a processor 450 connected to the plurality of pumps 430 and the blood glucose sensor 440 and configured to adjust delivery property of the at least one drug according to the measured blood glucose level of the patient; and wherein the plurality of pumps 430 are further configured by the processor 450 to adjust pumping the at least one drug according to the adjusted delivery property.

[0048] FIG. 7 is a block diagram for a system 500 for chemotherapy delivery according to another embodiment of the invention. The system 500 comprise a plurality of cartridges 520, a plurality of pumps 530, a blood glucose sensor 540, which are respectively similar to the plurality of cartridges 420, the plurality of pumps 430, the blood glucose sensor 440 shown in FIG. 6. Alternatively, one of the plurality of cartridges 420 contains saline, and the system 400 further comprises a mixer 555 connected to the plurality of cartridges 520 and the processor 550 and configured to dilute the at least one drug by diluting the insulin, the glucose and the at least one chemotherapeutic drug with the saline according to the adjusted delivery property, wherein the mixer 550 is further configured to deliver the diluted drug to the patient.

[0049] Alternatively, the system 500 further comprises an ECG monitoring system 560 communicatively coupled to the processor 550 and configured to monitor heart rhythm of the patient. The processor 550 is further configured to adjust the delivery property of the at least one drug according to the measured blood glucose level and the heart rhythm of the patient; wherein the plurality of pumps 530 are further configured by the processor 550 to adjust pumping the at least one drug according to the adjusted delivery property. [0050] Alternatively, the ECG monitoring system 560 is further configured to indicate to the processor 550 that an adverse cardiac event is detected for the patient; and the processor 550 is further configured to instruct the plurality of pumps 530 to return the patient to normal blood glucose levels by changing the amount for pumping for insulin, and/or glucose.

[0051] Alternatively, the processor 550 is further communicatively connected to a server 565 and the processor 550 is further configured to download patient data from the sever 565; wherein the plurality of pumps 530 are further configured by the processor 550 to adjust pumping the at least one drug according to the patient data.

[0052] Alternatively, each of the plurality of slots 510 includes a chamber sized to receive the corresponding one of a plurality of cartridges.

[0053] Alternatively, the system 500 further comprises a display 565 communicatively coupled to both the ECG monitoring system 560 and the blood glucose sensor 540, and configured to show a current blood glucose levels and ECG status according to data received from the ECG monitoring system 560 and the blood glucose sensor 540.

[0054] Alternatively, the system 500 further comprises a pressure sensor 570 connected to the plurality of pumps 530 and configured to stop pumping of the plurality of pumps 530 if the pressure sensor 570 detects a blood pressure of the patient is higher than a threshold.

[0055] Alternatively, the system 500 further comprises a waste container 575, an air detector 580 connected to both the waste container 575 and an output line of the plurality of pumps 530 and configured to remove air from the output line into the waste container 575.

[0056] Alternatively, the system 500 further comprises a heater 585 placed in proximity to the plurality of cartridges 520 and configured to remove condensation in the at least one of the plurality of cartridges 520 by heating the at least one of the plurality of cartridges 520 to room temperature.

[0057] Alternatively, the delivery property of the at least one drug comprises the flow rate of drug delivery and volume of drug delivery, treatment time, treatment remaining, medication being administered, remaining medication to administer, medication administered, medication duration, order of drugs to be delivered.

[0058] FIG. 8 is a block diagram illustrating the processing system 600. The processing system 600 includes protocol logic 605, cartridge logic 610, display logic (which can include GUI logic), pump logic 620, glucose logic 625, ECG logic 630, mixer logic 635, and communications logic 640.

[0059] During operation of the apparatus, the protocol logic 605 receives a protocol for a patient, either via manual entry (via an input device such as a GUI) or wired or wirelessly via the communications logic 640. In an embodiment, the protocol logic 605 can verify the protocol matches the type and/or stage of cancer. For example, breast cancer chemo should be

administered for a breast cancer patient and not for a lung cancer patient. This verification can occur by checking a database within the apparatus and/or checking an external database in conjunction with the communications logic 640. In another embodiment, a user can enter the type of cancer and/or stage and receive a recommended protocol, which the user can then accept. Once the protocol is received, it is displayed by the display logic 615 on the display and in an embodiment, a user can accept the protocol (e.g., confirm it is correct for the correct person and affirmatively acknowledge it to prevent administering an incorrect medication to a patient).

[0060] Once protocol data is received/accepted, the cartridge logic 610 can indicate which cartridge goes into which pump by indicating the same via text and/or colors (e.g., cartridges and pumps can be color coded) adjacent the pumps and/or on the display. For example, the display could state insert an insulin cartridge in the leftmost pump and a display at the pump might read insulin and/or be color coded. Note that at least some of the pumps could have static labelling indicating the type of cartridge if that pump always using the same contents (e.g., the leftmost pump may always be used for insulin so an active display would not be needed).

[0061] In an embodiment, the above operation can be performed automatically without any human interaction. For example, upon the display states to insert an insulin cartridge in the leftmost pump, a robotic arm is programmed to insert an insulin cartridge in the leftmost pump according to predetermined instructions and the statement on the display.

[0062] Once a cartridge is inserted, the cartridge logic 610 further reads an identifying mechanism on each inserted cartridge to verify the correct cartridge is inserted in the respective pumps. Alternatively or in addition, the pump could be configured and/or shaped to accept only specific cartridges based on contents. The mechanism may be a bar code, RFID, magnetic strip, hologram, etc. In an embodiment, in conjunction with the communications logic 640, the cartridge logic 610 can contact a database to verify the authenticity of the cartridge and/or verify the cartridge is not being reused, which could lead to contamination problems and/or being refilled with counterfeit medication. For example, if a cartridge ID is not in the database, the cartridge is most likely counterfeit, meaning safety issues for the patient. If the cartridge ID is in the database but indicated as previously used, then cartridge could be counterfeit or refilled with potentially fake, contaminated, and/or unauthorized medications. If the verification fails, then the display logic 615 can present a warning re same and prevent administration of the cartridge contents. If verification passes, the database then updates itself to indicate the cartridge has been used.

[0063] In an embodiment, the cartridge logic 610 checks for an expiration date of the cartridge and will not enable the apparatus if a cartridge has expired.

[0064] In an embodiment, identification information that for example, the cartridge logic 610 uses to verify the authenticity of the cartridge and/or verify the cartridge is not being reused includes a checksum or other scheme to verify authenticity. This can be useful when it is not possible to connect with a database.

[0065] The display logic 615 displays messages and other information on the display. It receives the data to display from the other components of the apparatus, either directly or via the processing system. The display logic 615 can display ECG data, blood glucose data,

administration instructions, progress information (e.g., phase information, hypoglycemic time, treatment time, treatment remaining, blood glucose level; medication being administered, remaining medication to administer, medication administered, etc.), patient data, protocol data, etc.

[0066] After the protocol has been received and the cartridge logic 610 verifies the cartridges, the pump logic 620 begins administration of the cartridge contents per the received protocol. During the administration, the protocol logic 605 updates the display with status of the administration. The administration, as discussed previously, includes administering of insulin to lower glucose blood levels and then administering the drugs. Note that the pump logic 620 may pump some or all of the cartridge content into the mixer before administering to the patient. For example, chemotherapy drugs and saline may be first pumped into the mixer before

administering the mix to the patient. The glucose logic 625 receives blood glucose levels from the blood glucose monitor. The display logic 615 displays the blood glucose levels on the display. If the glucose logic 625 determines that blood glucose level is too low (e.g., 2.2 mmol/L), it will cause the pump logic 620 to administer glucose to the patient to increase the blood glucose level. Similarly, the ECG logic 630 receives data from the ECG monitor and if data is abnormal, will notify the glucose logic 625, which will in turn administer glucose as described above. Also note that in either case the glucose logic 640 or ECG logic 630 can cause the apparatus to issue a warning (audio, video, and/or text, etc.). In this case, a user can also manually administer glucose. Further, at completion of the protocol, the glucose logic 625 will cause the pump logic 620 to administer glucose to raise blood glucose levels to normal levels (e.g., > 5.4 mmol/L).

[0067] The mixer logic 635 controls the mixer to mix the contents of the cartridges per the protocol. The mixer then administers the mix to the patient.

[0068] The communications logic 640 interacts via wired or wireless connection to receive a patient protocol and to interact with a database or databases per above.

[0069] FIG. 9 is a high-level extent diagram showing an example of an architecture 700 of the system 300 of FIG. 5. The architecture 700 includes one or more processors 710 and memory 720 coupled to an interconnect 760. The interconnect 760 shown in FIG. 9 is an abstraction that represents any one or more separate physical buses, point to point connections, or both, connected by appropriate bridges, adapters, or controllers. The interconnect 760, therefore, may include, for example, a system bus, a form of Peripheral Component Interconnect (PCI) bus, a HyperTransport or industry standard architecture (ISA) bus, a small computer system interface (SCSI) bus, a universal serial bus (USB), IIC (I2C) bus, or an Institute of Electrical and

Electronics Engineers (IEEE) standard 1394 bus, also called "Firewire", and/or any other suitable form of physical connection.

[0070] The processor(s) 710 is/are the central processing unit (CPU) of the architecture 700 and, thus, control the overall operation of the architecture 700. In certain embodiments, the processor(s) 710 accomplish this by executing software or firmware stored in memory 720, which would therefore store the logics of FIG. 8, for example, protocol logics 605, cartridge logic 610, display logic 615, etc. The processor(s) 710 may be, or may include, one or more programmable general-purpose or special-purpose microprocessors, digital signal processors (DSPs), programmable controllers, application specific integrated circuits (ASICs),

programmable logic devices (PLDs), or the like, or a combination of such devices.

[0071] The memory 720 is or includes the main memory of the architecture 700. The memory 720 represents any form of random access memory (RAM), read-only memory (ROM), flash memory, or the like, or a combination of such devices. In use, the memory 720 may contain, among other things, software or firmware code for use in implementing at least some of the embodiments of the invention introduced herein.

[0072] Also connected to the processor(s) 710 through the interconnect 760 is a communications interface, such as, but not limited to, a network adapter 740, one or more output device(s) 730 (e.g., the display of FIG. 5) and one or more input device(s) 750 (e.g., the display of FIG. 5 if touch sensitive). The network adapter 740 provides the architecture 700 with the ability to communicate with remote devices over the interconnect network 730 and may be, for example, an Ethernet adapter or Fiber Channel adapter. The input device 750 may include a touch screen, keyboard, and/or mouse, etc. The output device 730 may include a screen and/or speakers, etc.

[0073] The techniques introduced herein can be implemented by programmable circuitry programmed/configured by software and/or firmware, or entirely by special-purpose circuitry, or by a combination of such forms. Such special-purpose circuitry (if any) can be in the form of, for example, one or more application-specific integrated circuits (ASICs), programmable logic devices (PLDs), field-programmable gate arrays (FPGAs), etc.

[0074] Software or firmware to implement the techniques introduced here may be stored on a machine-readable storage medium and may be executed by one or more general-purpose or special-purpose programmable microprocessors. A "machine-readable medium", as the term is used herein, includes any mechanism that can store information in a form accessible by a machine (a machine may be, for example, a computer, network device, cellular phone, personal digital assistant (PDA), manufacturing tool, any device with one or more processors, etc.). For example, a machine-accessible medium includes recordable/non-recordable media (e.g., readonly memory (ROM); random access memory (RAM); magnetic disk storage media; optical storage media; flash memory devices; etc.), etc.

[0075] The term "logic", as used herein, means: a) special-purpose hardwired circuitry, such as one or more application-specific integrated circuits (ASICs), programmable logic devices (PLDs), field programmable gate arrays (FPGAs), or other similar device(s); b) programmable circuitry programmed with software and/or firmware, such as one or more programmed general- purpose microprocessors, digital signal processors (DSPs) and/or microcontrollers, or other similar device(s); or c) a combination of the forms mentioned in a) and b). [0076] FIG. 10 is a flowchart illustrating of method of operation of the apparatus. In an embodiment, the logics of FIG. 8 can carry out the method. First, in block 805, protocol data is received. The protocol data includes, for example, medications (e.g., cancer therapy, insulin) and other agents (e.g., saline, glucose) to administer in order and duration and/or in combination. Examples protocols can be found in WO 2012/075679A1 attached hereto. In block 810, the protocol can then optionally be verified per above. In block 815, cartridge slots are then indicated which slots/pumps for which cartridges for each medication and agent, etc. In block 820, cartridges are then verified for authenticity, reuse, and/or expiration, etc. After verification, the method can include notifying a database to update cartridge records as used so as to prevent future refill and reuse.

[0077] In block 825, insulin is then administered to lower blood glucose level, which is monitored throughout the method. Insulin is continuously administered until a low blood glucose level is achieved (e.g., to 2.8 - 4.5 mmol/L or 2.2 mmol/L). When the method 800 determines that the blood glucose level is adequate, the method 800 proceeds with blocks 835 and 840, saline and medication (e.g., chemo) is mixed and the mix is administered. If the method 800 determines that the blood glucose level is not adequate, the method 800 goes back to block 825 to continue to administering insulin. Note that insulin can be continuously

administered to maintain a target blood glucose level.

[0078] During the administration, as blood glucose levels are constant monitored, the method 800 determines if the blood glucose level is low in block 845. If the blood glucose falls below a predetermined level (e.g., 2.2 mmol/L), glucose is administered in block 855 to raise blood glucose levels. Further, during the method 800, if ECG is continuously monitored and if abnormal in block 850, glucose can be administered in block 855. Note that if the blood glucose falls too low and/or ECG is abnormal, the method can include performing a warning with sound and/or visually (e.g., on the display). The method then ends. Note that many portions of the method can be performed substantially simultaneously and/or in a different order than presented. Further, some portions can be omitted.

[0079] FIG. 11 is a flow diagram illustrating an example of method 900 of chemotherapy delivery according to an embodiment of the invention.

[0080] The method 900 comprises receiving, in block 905, by each of a plurality of slots, a corresponding one of a plurality of cartridges; pumping, in block 910,by a plurality of pumps each configured to be connected to the corresponding one of the plurality of cartridges, at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol. The at least one drug includes insulin, glucose and at least one

chemotherapeutic drug, and the plurality of the cartridges are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively. The method 900 further comprises measuring, in block 915, by a blood glucose sensor communicatively coupled to the plurality of pumps, a blood glucose level of the patient; adjusting, in block 920, by a processor connected to the plurality of pumps and the blood glucose sensor, delivery property of the at least one drug according to the measured blood glucose level of the patient; and adjusting, in block 925, by the plurality of pumps, pumping the at least one drug according to the adjusted delivery property.

[0081] Alternatively, the method 900 further comprises (not showing in FIG. 11) diluting, by a mixer connected to the plurality of cartridges and the processor, the at least one drug by diluting the insulin, the glucose and the at least one chemotherapeutic drug according to the adjusted delivery property, and delivering, by the mixer, the diluted drug to the patient.

[0082] Alternatively, the method 900 further comprises (not showing in FIG. 11) monitoring, by an ECG monitoring system communicatively coupled to the processor, heart rhythm of the patient; adjusting, by the processor, the delivery property of the at least one drug according to the measured blood glucose level and the heart rhythm of the patient; and adjusting, by the plurality of pumps, pumping the at least one drug according to the adjusted delivery property.

[0083] Alternatively, the method 900 further comprises (not showing in FIG. 11) indicating, by the ECG monitoring system, to the processor that an adverse cardiac event is detected for the patient; and instructing, by the processor to the plurality of pumps, to return the patient to normal blood glucose levels by changing the amount for pumping for insulin, and/or glucose.

[0084] Alternatively, the method 900 further comprises (not showing in FIG. 11) downloading, by the processor communicatively connected to a server, patient data from the sever; adjusting, by the plurality of pumps, pumping of the at least one drug according to the patient data.

[0085] Alternatively, each of the plurality of pumps includes a chamber sized to receive the corresponding one of a plurality of cartridges.

[0086] Alternatively, the method 900 further comprises (not showing in FIG. 11) showing, by a display communicatively coupled to both the ECG monitoring system and the blood glucose sensor, a current blood glucose levels and ECG status according to data received from the ECG monitoring system and the blood glucose sensor.

[0087] Alternatively, the method 900 further comprises (not showing in FIG. 11) stopping, by a pressure sensor connected to the plurality of pumps, pumping of the plurality of pumps if the pressure sensor detects a blood pressure of the patient is higher than a threshold.

[0088] Alternatively, the method 900 further comprises (not showing in FIG. 11) removing, by an air detector connected to both a waste container and an output line of the plurality of pumps, air from the output line into the waste container.

[0089] Alternatively, the method 900 further comprises (not showing in FIG. 11) removing, by a heater placed in proximity to the plurality of cartridges, condensation in the at least one of the plurality of cartridges by heating the at least one of the plurality of cartridges to room

temperature.

[0090] Alternatively, the delivery property of the at least one drug comprises the flow rate of drug delivery and volume of drug delivery, treatment time, treatment remaining, medication being administered, remaining medication to administer, medication administered, medication duration, order of drugs to be delivered.

[0091] According to another embodiment, a computer readable storage medium, storing instructions when executed by a processor, cause the computer to perform operations comprising: controlling, a plurality of pumps each being configured to be connected to a corresponding one of a plurality of cartridges to pump at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol, wherein the at least one drug includes insulin, glucose and at least one chemotherapeutic drug, and the plurality of the cartridges are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively; controlling a blood glucose sensor communicatively coupled to the plurality of pumps to measure a blood glucose level of the patient; adjusting delivery property of the at least one drug according to the measured blood glucose level of the patient; and controlling the plurality of pumps to adjust pumping the at least one drug according to the adjusted delivery property.

[0092] Alternatively, one of the plurality of cartridges contains saline, and the operations further comprises controlling a mixer connected to the plurality of cartridges and the processor to dilute the at least one drug by diluting the insulin, the glucose and the at least one chemotherapeutic drug with the saline according to the adjusted delivery property, and controlling the mixer to deliver the diluted drug to the patient by adjusting a flow rate and volume of the delivered diluted drug.

[0093] Alternatively, the operations further comprises reading heart rhythm of the patient monitor monitored by an ECG monitoring system communicatively coupled to the processor; adjusting the delivery property of the at least one drug according to the measured blood glucose level and the heart rhythm of the patient; and controlling the plurality of pumps to adjust pumping the at least one drug according to the measured blood glucose level and the heart rhythm of the patient to maintain proper blood sugar level.

[0094] Alternatively, the operations further comprises monitoring a detection of an adverse cardiac event for the patient from the ECG monitoring system; and instructing the plurality of pumps to return patient to normal blood glucose levels by changing the amount for pumping for insulin, and/or glucose.

[0095] Alternatively, the operations further comprises downloading patient data from the sever; controlling the plurality of pumps to adjust pumping the at least one drug according to the patient data; and storing the adjusted delivery property in a data storage.

[0096] Alternatively, the operations further comprises controlling a display communicatively coupled to both the ECG monitoring system and the blood glucose sensor, to show a current blood glucose levels and ECG status according to data received from the ECG monitoring system and the blood glucose sensor.

[0097] Alternatively, the operations further comprises controlling an audio communicatively coupled to both the ECG monitoring system and the blood glucose sensor, to output an audio signal indicates a current blood glucose levels and ECG status according to data received from the ECG monitoring system and the blood glucose sensor.

[0098] References in this description to "an embodiment", "one embodiment", or the like, mean that the particular feature, function, structure or characteristic being described is included in at least one embodiment of the present invention. Occurrences of such phrases in this specification do not necessarily all refer to the same embodiment. On the other hand, such references are not necessarily mutually exclusive either.

[0099] Note that any and all of the embodiments described above can be combined with each other, except to the extent that it may be stated otherwise above or to the extent that any such embodiments might be mutually exclusive in function and/or structure. References

All of the references listed below and all of those cited in the specification above are hereby incorporated in their entirety by reference as if fully set forth herein.

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Vaughn AE, Deshmukh M. Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c. Nature cell biology. 2008 Dec 1 ; 10(12): 1477-83.

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Claims

CLAIMS We Claim:

1. A system for chemotherapy delivery, comprising:

a plurality of slots, wherein each of the plurality of slots is configured to receive a corresponding one of a plurality of cartridges;

a plurality of pumps, wherein each of the plurality of pumps is configured to be connected to the corresponding one of the plurality of cartridges, and the plurality of pumps are configured to pump at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol, wherein the at least one drug includes insulin, glucose and at least one chemotherapeutic drug, and the plurality of the cartridges are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively;

a blood glucose sensor communicatively coupled to the plurality of pumps, and configured to measure a blood glucose level of the patient;

a processor connected to the plurality of pumps and the blood glucose sensor and configured to adjust a delivery property of the at least one drug according to the measured blood glucose level of the patient; and

wherein the plurality of pumps are further configured by the processor to adjust pumping the at least one drug according to the adjusted delivery property.

2. The system of claim 1, wherein one of the plurality of cartridges contains saline, and the system further comprises:

a mixer connected to the plurality of cartridges and the processor and configured to dilute the at least one drug by diluting the insulin, the glucose and the at least one chemotherapeutic drug with the saline according to the adjusted delivery property, wherein the mixer is further configured to deliver the diluted drug to the patient.

3. The system of claim 1, further comprising

an ECG monitoring system communicatively coupled to the processor and configured to monitor heart rhythm of the patient;

wherein the processor is further configured to adjust the delivery property of the at least one drug according to the measured blood glucose level and the heart rhythm of the patient; wherein the plurality of pumps are further configured by the processor to adjust pumping the at least one drug according to the adjusted delivery property .

4. The system of claim 3, wherein

the ECG monitoring system is further configured to indicate to the processor that an adverse cardiac event is detected for the patient; and

the processor is further configured to instruct the plurality of pumps to return the patient to normal blood glucose levels by changing the amount for pumping for insulin, and/or glucose.

5. The system of claim 1, wherein

the processor is further communicatively connected to a server and configured to download patient data from the sever;

wherein the plurality of pumps are further configured by the processor to adjust pumping the at least one drug according to the patient data.

6. The system of claim 1,

wherein each of the plurality of slots includes a chamber sized to receive the corresponding one of a plurality of cartridges.

7. The system of claim 3, further comprising

a display communicatively coupled to both the ECG monitoring system and the blood glucose sensor, and configured to show a current blood glucose levels and ECG status according to data received from the ECG monitoring system and the blood glucose sensor.

8. The system of claim 1, further comprising

a pressure sensor connected to the plurality of pumps and configured to stop pumping of the plurality of pumps if the pressure sensor detects a blood pressure of the patient is higher than a threshold.

9. The system of claim 1, further comprising

a waste container; an air detector connected to both the waste container and an output line of the plurality of pumps and configured to remove air from the output line into the waste container.

10. The system of claim 1, further comprising a heater placed in proximity to the plurality of cartridges and configured to remove condensation in the at least one of the plurality of cartridges by heating the at least one of the plurality of cartridges to room temperature.

11. The system of claim 1, wherein the delivery property of the at least one drug comprises the flow rate of drug delivery, volume of drug delivery, treatment time, treatment remaining, medication being administered, remaining medication to administer, medication administered, medication duration, order of drugs to be delivered, wherein the treatment protocol includes at least one of medications and agents to administer and duration and their combination.

12. The system of claim 1, wherein the processor is further configured to control blood sugar levels for an extended period of time by using glucose clamps technique.

13. The system of claim 12, wherein the processor is further configured to control blood sugar levels to induce hypoglycemia for up to two hours by using the glucose clamps technique.

14. The system of claim 1, wherein the plurality of pumps are further configured by the processor to adjust pumping the at least one drug according to the adjusted delivery property before a hypoglycemic therapeutic window induced by a hypoglycemic glucose clamp.

15. The system of claim 1, wherein the plurality of pumps are further configured by the processor to adjust pumping the at least one drug according to the adjusted delivery property before a hypoglycemic therapeutic window induced by a hypoglycemic glucose clamp.

16. A method for chemotherapy delivery, comprising:

receiving, by each of a plurality of slots, a corresponding one of a plurality of cartridges; pumping, by a plurality of pumps each connected to the corresponding one of the plurality of cartridges, at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol, wherein the at least one drug includes insulin, glucose and at least one chemotherapeutic drug, and the plurality of the cartridges are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively;

measuring, by a blood glucose sensor communicatively coupled to the plurality of pumps, a blood glucose level of the patient;

adjusting, by a processor connected to the plurality of pumps and the blood glucose sensor, delivery property of the at least one drug according to the measured blood glucose level of the patient; and

adjusting, by the plurality of pumps, pumping the at least one drug according to the adjusted delivery property.

17. The method of claim 16, further comprising

diluting, by a mixer connected to the plurality of cartridges and the processor, the at least one drug by diluting the insulin, the glucose and the at least one chemotherapeutic drug according to the adjusted delivery property, and

delivering, by the mixer, the diluted drug to the patient.

18. The method of claim 16, further comprising

monitoring, by an ECG monitoring system communicatively coupled to the processor, heart rhythm of the patient;

adjusting, by the processor, the delivery property of the at least one drug according to the measured blood glucose level and the heart rhythm of the patient; and

adjusting, by the plurality of pumps, pumping the at least one drug according to the adjusted delivery property.

19. The method of claim 18, further comprising

indicating, by the ECG monitoring system, to the processor that an adverse cardiac event is detected for the patient; and

instructing, by the processor to the plurality of pumps, to return the patient to normal blood glucose levels by changing the amount for pumping for insulin, and/or glucose.

20. The method of claim 16, further comprising

downloading, by the processor communicatively connected to a server, patient data from the sever;

adjusting, by the plurality of pumps, pumping of the at least one drug according to the patient data.

21. The method of claim 16,

wherein each of the plurality of pumps includes a chamber sized to receive the

corresponding one of a plurality of cartridges.

22. The method of claim 18, further comprising

showing, by a display communicatively coupled to both the ECG monitoring system and the blood glucose sensor, a current blood glucose levels and ECG status according to data received from the ECG monitoring system and the blood glucose sensor.

23. The method of claim 16, further comprising

stopping, by a pressure sensor connected to the plurality of pumps, pumping of the plurality of pumps if the pressure sensor detects a blood pressure of the patient is higher than a threshold.

24 The method of claim 16, further comprising

removing, by an air detector connected to both a waste container and an output line of the plurality of pumps, air from the output line into the waste container.

25. The method of claim 16, further comprising

removing, by a heater placed in proximity to the plurality of cartridges, condensation in the at least one of the plurality of cartridges by heating the at least one of the plurality of cartridges to room temperature.

26. The method of claim 16, wherein the delivery property of the at least one drug comprises the flow rate of drug delivery and volume of drug delivery, treatment time, treatment remaining, medication being administered, remaining medication to administer, medication administered, medication duration, order of drugs to be delivered, wherein the treatment protocol includes at least one of medications and agents to administer and duration and their combination.

27. The method of claim 16, further comprising controlling, by the processor, blood sugar levels for an extended period of time by using glucose clamps technique.

28. The method of claim 27, further comprising controlling, by the processor, blood sugar levels to induce hypoglycemia for up to two hours by using the glucose clamps technique.

29. The method of claim 16, further comprising adjusting by the plurality of pumps, pumping the at least one drug according to the adjusted delivery property before a hypoglycemic therapeutic window induced by a hypoglycemic glucose clamp.

30. The method of claim 16, further comprising adjusting by the plurality of pumps, pumping the at least one drug according to the adjusted delivery property before a hypoglycemic therapeutic window induced by a hypoglycemic glucose clamp.

31. A computer readable storage medium, storing instructions when executed by a processor, cause the computer to perform operations comprising:

controlling, a plurality of pumps each connected to a corresponding one of a plurality of cartridges to pump at least one drug contained in at least one of the plurality of cartridges to a patient according to a treatment protocol, wherein the at least one drug includes insulin, glucose and at least one chemotherapeutic drug, and the plurality of the cartridges are configured to contain insulin, glucose and the at least one chemotherapeutic drug respectively;

controlling a blood glucose sensor communicatively coupled to the plurality of pumps to measure a blood glucose level of the patient;

adjusting delivery property of the at least one drug according to the measured blood glucose level of the patient; and

controlling the plurality of pumps to adjust pumping the at least one drug according to the adjusted delivery property.

32. The computer readable storage medium of claim 31, wherein one of the plurality of cartridges contains saline, and the operations further comprises:

controlling a mixer connected to the plurality of cartridges and the processor to dilute the at least one drug by diluting the insulin, the glucose and the at least one chemotherapeutic drug with the saline according to the adjusted delivery property, and

controlling the mixer to deliver the diluted drug to the patient by adjusting a flow rate and volume of the delivered diluted drug.

33. The computer readable storage medium of claim 31, wherein the operations further comprises

reading heart rhythm of the patient monitor monitored by an ECG monitoring system communicatively coupled to the processor;

adjusting the delivery property of the at least one drug according to the measured blood glucose level and the heart rhythm of the patient;

controlling the plurality of pumps to adjust pumping the at least one drug according to the measured blood glucose level and the heart rhythm of the patient to maintain proper blood sugar level.

34. The computer readable storage medium of claim 31, wherein the operations further comprises

monitoring a detection of an adverse cardiac event for the patient from the ECG monitoring system; and

instructing the plurality of pumps to return patient to normal blood glucose levels by changing the amount for pumping for insulin, and/or glucose.

35. The computer readable storage medium of claim 31, wherein the operations further comprises

downloading patient data from the sever;

controlling the plurality of pumps to adjust pumping the at least one drug according to the patient data; and

storing the adjusted delivery property in a data storage.

36. The computer readable storage medium of claim 31, wherein the operations further comprises

controlling a display communicatively coupled to both the ECG monitoring system and the blood glucose sensor, to show a current blood glucose levels and ECG status according to data received from the ECG monitoring system and the blood glucose sensor.

37. The computer readable storage medium of claim 31, wherein the operations further comprises

controlling an audio communicatively coupled to both the ECG monitoring system and the blood glucose sensor, to output an audio signal indicates a current blood glucose levels and ECG status according to data received from the ECG monitoring system and the blood glucose sensor.

38. The computer readable storage medium of claim 31, wherein the operations further comprises

controlling blood sugar levels for an extended period of time by using glucose clamps technique.

39. The computer readable storage medium of claim 38, wherein the operations further comprises

controlling blood sugar levels to induce hypoglycemia for up to two hours by using the glucose clamps technique.

40. The computer readable storage medium of claim 31, wherein the operations further comprises

controlling a plurality of pumps to adjust pumping the at least one drug according to the adjusted delivery property before a hypoglycemic therapeutic window induced by a

hypoglycemic glucose clamp.

41. The computer readable storage medium of claim 31, wherein the operations further comprises controlling a plurality of pumps to adjust pumping the at least one drug according to the adjusted delivery property before a hypoglycemic therapeutic window induced by a hypoglycemic glucose clamp.