Patent Application
20140066726
The present disclosure is related generally to a biological sample collection device for remote management of disease. In particular, the present disclosure is related to a wearable biological sample collection device for periodic sampling of analytes at a processing facility.
The remote management of disease, particularly chronic disease, requires information about the state of health of a subject. Some indications of the health of the subject can be derived from existing wearable diagnostic and monitoring devices. In particular, Holter recorders can inform a caregiver of the heart rate, sleep apnea monitors can record and communicate unusual breathing patterns, and these metrics plus the activity of the subject can be monitored by existing devices by Proteus Biomedical, Inc. of Redwood City, Calif. Some wearable diagnostic and monitoring devices are known as body-associated receivers or simply patches. Although the above described metrics are undeniably useful, and sometimes lifesaving, disease management also requires knowledge of chemical indicators of health. Examples of chemical health indices include the blood glucose of diabetics, creatinine levels in dialysis patients, or serum drug levels in many conditions. While there is ongoing extensive research on wearable chemical or biochemical sensors, few of these devices have made it out of the laboratory. Shortcomings of existing chemical/biochemical sensors include insufficient accuracy, inadequate specificity, poor repeatability, short operating life, complexity, and excessive cost.
In one aspect, a biological sample collection device includes a top cover plate, a bottom portion attached to the top cover plate, and a fastening portion provided on the bottom portion. The bottom portion includes a remotely-analyzable biological sample collection portion to collect a biological sample from a body of a subject. The biological sample is to be analyzed at a remote processing facility at a later time. The fastening portion affixes the remotely-analyzable biological sample collection device to the body of the subject. A real-time clock is coupled to the top cover plate and a memory also coupled to the top cover plate is electrically coupled to the real time clock.
In another aspect, a remotely-analyzable biological sample collection system further includes a processing unit, at least two electrodes, and a transbody conductive communication module. The at least two electrodes are coupled to the processing unit and are configured to contact the skin of a subject. The transbody conductive communication module is coupled to the processing unit and the at least two electrodes. The transbody conductive communication module is operative to detect and gather physiological information from the subject in the form of an electric current flow through the at least two electrodes at a first frequency. The current flow at the first frequency is associated with a device associated with the subject.
In yet another aspect, a remotely-analyzable biological sample collection system further includes a physiological sensing module coupled to the processing unit and a wireless communication module. The physiological sensing module is operative to sense physiological information from the subject in the form of electric current flow through the at least two electrodes at a second frequency. The current flow at the second frequency is associated with the physiology of the subject. The wireless communication module is coupled to the processing unit and is operative to communicate information from the remotely-analyzable biological collection device to a communication device external to the subject.
The present specification describes multiple aspects of a biological sample collection device, biological sample collection system, and a communication system therefore, for remote management of disease. In one aspect, the biological sample collection device can be realized in the form of a patch that may be positioned on a subject. In various aspects, the biological sample collection device can be used for periodic sampling of biological or biochemical/chemical substance constituents, e.g., analytes, secreted by the subject and collected by the biological sample collection device over a predetermined period. The analytes can be determined using an analytical procedure at a processing facility. In various aspects, the biological sample collection device may be wearable, implantable, or semi-implantable on the or in the subject. In one aspect, the biological sample collection device may be combined in a system with receivers. In other aspects, the biological sample collection device may be combined with sensing and recording elements. In other aspects, the biological sample collection device may be combined in a communication system. Examples of communication systems include receivers to detect information from the subject encoded in current flows through a conducting solution and systems capable of communicating with one or more of the communication devices.
Various aspects of the disclosed biological sample collection device and systems may have particular utility in places where the cost of healthcare is a real challenge such as underdeveloped countries where continuous cell phone coverage and even going to a hospital to have a lab test may be impractical. The disclosed biological sample collection device and systems, however, provide a method for collecting physiological information and analyzing the information remotely so that a caregiver does not need to be located near the subject or even in the same continent as the subject.
In a passive configuration, the biological sample collection device 100 includes passive elements that merely collect physiological information (e.g., physiological parameters or biomarkers) over a predetermined period for later analysis at a processing facility. The passive configuration does not employ sensors, receivers, electronic recording devices, memory, communication capabilities, or batteries. In one aspect, the biological sample collection device 100 may comprise one or more passive physiological parameter collection abilities. By physiological parameter collection ability is meant a capability of collecting a physiological parameter or biomarker including but not limited to: chemical composition of fluid, e.g., analyte in blood, perspiration (sweat), extra-cellular fluid, excreted oils, skin cells, hair follicles, viruses, bacteria, antibodies, DNA, molecules of various sizes associated with the subject 102. In various aspects, the biological sample collection device 100 may be configured to collect small molecules or elements like potassium, sodium, alcohol, nicotine, and other drugs of abuse to assist addicts; larger molecules like glucose and proteins like antibodies and DNA; and particles like viruses and bacteria. The term “biomarker” refers to an anatomic, physiologic, biochemical, or molecular parameter associated with the presence and severity of specific disease states.
In an active configuration, the biological sample collection device 100 comprises one or more active components to dynamically detect and gather physiological parameters in addition to passively collecting physiological parameters or biomarkers. In one aspect, active components include but are not limited to: sensors, receivers, electronic recording devices, memory, communication components. In an active configuration, the biological sample collection device 100 may include an on-board battery to supply electrical power to the active components. The biological sample collection device 100 may comprise a real time clock coupled to the cover plate to time-stamp (e.g., record in memory the date and/or time) when the data collection is actually performed. Active physiological parameter or biomarker sensing abilities include, without limitation, sensing: cardio-data, including heart rate, electrocardiogram (ECG), and the like; respiration rate, temperature; pressure; chemical composition of fluid, e.g., analyte in blood, fluid state, blood flow rate, accelerometer motion data.
The biological sample collection device 100 may comprise any number of distinct physiological parameter or biomarker collecting and/or sensing capabilities. The number of distinct parameters or biomarker collecting and/or sensing capabilities may vary e.g., one or more, two or more, three or more, four or more, five or more, ten or more, and so on.
The biological sample collection device 100 provides specific information about the state of health of the subject 102. Although some of this information may be derived from sensors embedded in the biological sample collection device 100 (e.g., active mode), there is a limitation in the sensor technology such that it is not practical to implement small ambulatory, inexpensive, biochemical/chemical sensors capable of being embedded in the biological sample collection device 100. As an example, there is no existing practical sensor for measuring viral load for a subject that is HIV positive and needs to control viral loads through entry retroviral medicines. Accordingly, instead of trying to embed sensors into a wearable device, the present disclosure provides a biological sample collection device 100 for collecting biological samples over a predetermined period, which then can be analyzed in a conventional way at a processing facility. The subject 102 may obtain the biological sample collection device 100 with a prescription, wear the biological sample collection device 100 for a prescribed period (e.g., minutes, hours, days, or weeks), and send it to a processing laboratory facility where the materials that were collected (e.g., biochemical/chemical samples) by the biological sample collection device 100 are removed and a suite of laboratory tests are conducted on the samples to measure any number of physiologic parameters and/or biomarkers or simply ascertain the presence or absence of a particular physiological parameter or biomarker. For instance, if the biological sample collection device 100 collected extra-cellular fluid, the laboratory could analyze the extra-cellular fluid for blood chemistry, glucose for the diabetics, creatinine for people on dialysis or recipients of organ transplant, and so on.
In one aspect, the subject 102 merely affixes the biological sample collection device 100 to the skin to collect raw physiological parameters or biomarkers (e.g., biological samples such as biochemicals/chemicals) in the field over several minutes, hours, days, weeks, or other suitable period. Since not all analytes require moment-by-moment measurement to optimize therapy, for those analytes for which periodic sampling is adequate, the limitations of biosensors can be overcome by configuring the biological sample collection device 100 not as an analysis tool but as a sample collection tool—a biological sample collection device. Once the relevant information is extracted from the biological sample collection device 100, the sample collection device 100 may be discarded.
The central processing facility 200 may use any suitable analytical procedures, such as a titration, for example, to analyze the analyte. In some aspects, conventional biochemical analysis techniques can be employed to extract and analyze the biological samples from the biological sample collection device 100. Such analytical techniques may include, for example, ELISA (enzyme linked immuno-assay), PCR (polymer chain reaction), FTIR (Fourier transform infrared spectroscopy), cell culture, mass spectroscopy, liquid chromatography, among other state of the art chemical analysis techniques. In one aspect, a reverse iontophoresis process may be used to drive the biochemicals/chemicals out of the collection device 100 and extract the analytes for analysis.
The adsorption, atoms, ions, biomolecules or molecules of gas, liquid, or dissolved solids from the body of the subject 102 adhere to the surface of the adsorbent material 302. This process creates a film of the adsorbate (the molecules or atoms being accumulated) on the surface of the adsorbent material 302. It differs from absorption, in which a fluid permeates or is dissolved by a liquid or solid. Similar to surface tension, adsorption is a consequence of surface energy. In the adsorbent material 302, all the bonding requirements (be they ionic, covalent, or metallic) of the constituent atoms of the material are filled by other atoms in the material. Atoms on the surface of the adsorbent material 302, however, are not wholly surrounded by other adsorbent atoms and therefore can attract adsorbates from the body of the subject 102 such as perspiration, blood, excreted oils, or other fluids. The adsorption process generally may be classified as physisorption (characteristic of weak van der Waals forces) or chemisorption (characteristic of covalent bonding). It may also occur due to electrostatic attraction. The adsorbent material 302 may be formed using many natural physical, biological, or chemical materials such as activated charcoal, synthetic resins, nanoporous carbon. Adsorption, ion exchange, and chromatography are sorption processes in which certain adsorbates are selectively transferred from the fluid phase to the surface of insoluble, rigid particles suspended in a vessel or packed in a column.
The real time clock 1602 and the memory 1604 record or time-stamp (e.g., record in memory the date and/or time) when the biological sample collection device is applied and/or removed from the body of the subject 102 (
In one aspect, the framework 1682 of the biological sample collection device 1600 provides a chassis for attaching, depositing upon, or securing multiple components. In one aspect, a material 1684 is physically associated with the framework 1682. The material 1684 may be chemically deposited on, evaporated onto, secured to, or built-up on the framework all of which may be referred to herein as “deposit” with respect to the framework 1682. The material 1684 is deposited on one side of the framework 1682. The materials of interest that can be used as material 1684 include, but are not limited to: Cu or Cul. The material 1684 is deposited by physical vapor deposition, electrodeposition, or plasma deposition, among other protocols. The material 1684 may be from about 0.05 to about 500 μm thick, such as from about 5 to about 100 μm thick. The shape is controlled by shadow mask deposition, or photolithography and etching. Additionally, even though only one region is shown for depositing the material, each of the biological sample devices 1600 may contain two or more electrically unique regions where the material 1684 may be deposited, as desired.
At a different portion of the same side of the framework 1682, another material 1686 is deposited, such that the first and second materials 1684 and 1686 are dissimilar and are separated by a non-conducting skirt 1619. More specifically, the first and second materials 1684 and 1686 are selected such that they form a voltage potential difference when in contact with a conducting liquid, such as body fluids secreted by the body of subject 102, for example. Thus, when the biological sample devices 1600 is in contact with and/or partially in contact with a conducting liquid on the surface of the body of the subject 102, a current path 1692 is formed through the conducting liquid between first and second material 1684 and 1686. Although not shown, in one aspect, the second material 1686 may be located opposite to the first material 1684. The scope of the present disclosure is not limited by the side selected and the term “different side” can mean any of the multiple sides that are different from the first selected side. Furthermore, although the shape of the system is shown as a square, the shape may be any geometrically suitable shape. The materials 1684 and 1686 are selected such that they produce a voltage potential difference when the biological collection device 1600 is in contact with a conducting liquid, such as body fluid, on the surface of the body of the subject 102 when the biological collection device 1600 is applied to the body of the subject 102. The materials of interest for material 1686 include, but are not limited to: Mg, Zn, or other electronegative metals. As indicated above with respect to the material 1684, the material 1686 may be chemically deposited on, evaporated onto, secured to, or built-up on the framework. Also, an adhesion layer may be necessary to help the material 1686 (as well as material 1684 when needed) to adhere to the framework 1682. Typical adhesion layers for the material 1686 are Ti, TiW, Cr or similar material. Anode material and the adhesion layer may be deposited by physical vapor deposition, electrodeposition or plasma deposition. The material 1686 may be from about 0.05 to about 500 μm thick, such as from about 5 to about 100 μm thick. However, the scope of the present disclosure is not limited by the thickness of any of the materials nor by the type of process used to deposit or secure the materials to the framework 1682.
According to the disclosure set forth, the materials 1684 and 1686 can be any pair of materials with different electrochemical potentials. Additionally, in the aspects wherein the system 1680 is used in-vivo, the materials 1684 and 1686 may absorbable by the body of the subject 102. More specifically, the materials 1684 and 1686 can be made of any two materials appropriate for the environment in which the biological collection device 1600 will be operating. For example, when the biological collection device 1600 is in contact with an ionic solution, such as perspiration. Suitable materials are not restricted to metals, and in certain aspects the paired materials are chosen from metals and non-metals, e.g., a pair made up of a metal (such as Mg) and a salt (such as CuCl or Cul). With respect to the active electrode materials, any pairing of substances—metals, salts, or intercalation compounds—with suitably different electrochemical potentials (voltage) and low interfacial resistance are suitable.
Materials and pairings of interest include, but are not limited to, those reported in TABLE 1 below. In one aspect, one or both of the metals may be doped with a non-metal, e.g., to enhance the voltage potential created between the materials as they come into contact with a conducting liquid. Non-metals that may be used as doping agents in certain aspects include, but are not limited to: sulfur, iodine, and the like. In another aspect, the materials are copper iodine (Cul) as the anode and magnesium (Mg) as the cathode. Aspects of the present disclosure use electrode materials that are not harmful to the human body.
Thus, when the biological collection device 1600 is in contact with a conducting fluid, a current path is formed through the conducting fluid between material 1684 and 1686. A control device 1688 is secured to the framework 1682 and electrically coupled to the materials 1684 and 1686. In one aspect, the control device 1688 includes electronic circuitry, for example the real time clock 1602 and memory 1604 capable of recording a time-stamp when the biological collection device 1600 is applied to the body of the subject 102 and the a control voltage is generated by the framework 1682. In other aspects, the control device 1688 may comprise logic is capable of performing additional functionality such as controlling and altering the conductance between the materials 1684 and 1686.
The voltage potential created between the materials 1684 and 1686 provides the power for operating the system as well as produces the current flow through the conducting fluid and the biological collection device 1600. In one aspect, the biological collection device 1600 operates in direct current mode. In an alternative aspect, the biological collection device 1600 controls the direction of the current so that the direction of current is reversed in a cyclic manner, similar to alternating current. As the conducting fluid or the electrolyte, where the fluid or electrolyte component is provided by a physiological fluid, e.g., perspiration, reaches the two materials 1684 and 1686 the path for current flow between the materials 1684 and 1686 is completed and, in one aspect, the current path through may be controlled by the control device 1688. Completion of the current path allows for the current to flow and in turn activate the real time clock 1602 and memory 1604 to record a time-stamp when the biological collection device 1600 is applied to the body of the subject 102.
In one aspect, the two materials 1684 and 1686 are similar in function to the two electrodes needed for a direct current power source, such as a battery. The conducting liquid acts as the electrolyte needed to complete the power source. The completed power source described is defined by the physical chemical reaction between the materials 1684 and 1686 of the biological collection device 1600 and the surrounding fluids of the body. The completed power source may be viewed as a power source that exploits reverse electrolysis in an ionic or a conduction solution such as gastric fluid, blood, or other bodily fluids and some tissues. Additionally, the environment may be something other than a body and the liquid may be any conducting liquid. For example, the conducting fluid may be salt water or a metallic based paint.
In certain aspects, the two materials 1684 and 1686 may be shielded from the surrounding environment by an additional layer of material. Accordingly, when the shield is dissolved and the two dissimilar materials are exposed to the target site, a voltage potential is generated.
In certain aspects, the complete power source or supply is one that is made up of active electrode materials, electrolytes, and inactive materials, such as current collectors, packaging. The active materials are any pair of materials with different electrochemical potentials. Suitable materials are not restricted to metals, and in certain aspects the paired materials are chosen from metals and non-metals, e.g., a pair made up of a metal (such as Mg) and a salt (such as Cul). With respect to the active electrode materials, any pairing of substances—metals, salts, or intercalation compounds—with suitably different electrochemical potentials (voltage) and low interfacial resistance are suitable.
A variety of different materials may be employed as the materials that form the electrodes. In certain aspects, electrode materials are chosen to provide for a voltage upon contact with the target physiological site, e.g., the outer skin of the subject 102, sufficient to drive the power source of the biological collection device 1600. In certain aspects, the voltage provided by the electrode materials upon contact of the metals of the power source with the target physiological site is 0.001 V or higher, including 0.01 V or higher, such as 0.1 V or higher, e.g., 0.3 V or higher, including 0.5 volts or higher, and including 1.0 volts or higher, where in certain aspects, the voltage ranges from about 0.001 to about 10 volts, such as from about 0.01 to about 10 V.
In various aspects, the biological sample collection devices 100, 300, 400, 500, 600, 700, 800, 1600 described in connection with respective
Various aspects of biological sample collection systems provide a method of connecting medication that a subject 102 takes daily to the Internet and to the communication device (e.g., telephone or wireless communication device such as a cell phone or smart phone) of the subject 102. The IEM is generally configured as a pill taken by the subject 102. The IEM comprises an integrated circuit microchip and/or sensors embedded on or in the medication capsule or tablet (pill). The microchip and its sensors are powered up when wetted, which generally occurs when the pill is ingested. When ingested, the microchip starts generating physiologic communications that propagate through the body, like an electrocardiogram (EKG) or electromyography (EMG), and are communicated through the body. Like an EKG, the physiologic communications can be picked up by a receiver located on the subject 102. Most often the receiver is located on a wearable patch stuck on the torso of the subject 102. The patch has electrodes which detect the physiologic communications coming from the pill, measures heart rate and other parameters, and includes an accelerometer to measure body angle and activity level. From those measurements, processing devices on the patch can derive other metrics like amount of exercise, step count, how much sleep the subject gets at night. The receiver also includes a radio that uplinks the subject information (data) to the Internet usually via the communication device of the subject 102. The information associated with the subject 102 is then routed to servers and sent back to the subject 102 via the communication device. The subject 102 can then see what medications they took, when they took them, how that compares to what they were prescribed, and can also see metrics of how well they are doing. The subject 102 also can choose to share that information with professional caregivers such as doctors, nurses, family caregivers, joint social networks of people that have similar conditions so they can compare notes on how they are feeling, what medications work for them, what strategies work to help to keep their health improving, and so on.
In addition to receiving a conductive form of communication, such as one communicated by an identifier of an ingestible event marker, the receiver may further include one or more distinct physiological sensing modules having physiological parameter sensing abilities. The physiological sensing module may be implemented to sense various physiological parameters or biomarkers, such as, but not limited to: cardio-data, including heart rate, electrocardiogram (ECG), and the like; respiration rate, temperature; pressure; chemical composition of fluid, analyte detection in blood, fluid state, blood flow rate, accelerometer motion data. Where the receiver has physiological parameter or biomarker sensing capability, the number of distinct parameters or biomarkers that the receiver may sense may vary, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 10 or more. The term “biomarker” refers to an anatomic, physiologic, biochemical, molecular or other parameter associated with the presence and severity of specific disease states. Biomarkers are detectable and measurable by a variety of methods including physical examination, laboratory assays and medical imaging. Depending on the particular aspect, the receiver may accomplish one or more of these sensing functions using the communication receiving element, e.g., using electrodes of the receiver for receiving communications and sensing applications, or the receiver may include one or more distinct sensing elements that are different from the communication receiving element. The number of distinct sensing elements that may be present on (or at least coupled to) the receiver may vary, and may be one or more, two or more, three or more, four or more, five or more, ten or more.
In certain aspects, the receiver includes a set of two or more, such as two or three, electrodes that provide for dual functions of receiving communications and sensing. For example, in addition to receiving communications, the electrodes can also serve additional sensing functions. In certain aspects, the electrodes are used to generate electrocardiogram data. From that data, there are many kinds of processing that can be done, e.g., to detect various cardiac events, such as tachycardia, fibrillations, heart rate. The obtained electrocardiogram data can be used to titrate medications, or be used for alerts when an important change or significant abnormality in the heart rate or rhythm is detected. This data is also helpful in certain aspects for monitoring heart rate in patients who do not have pacemakers or as an alternative to patients who might normally require a Holter monitor or a Cardiac Event Monitor, portable devices for continuously monitoring the electrical activity of the heart for 24 hours or other devices. An extended recording period is useful for observing occasional cardiac arrthymias that are difficult to identify in shorter time periods.
In various aspects, the biological sample collection systems may comprise sensors, electronic recording devices, memory, communication components, an on-board battery to supply electrical power to the active components, a real time clock to time-stamp the time when the data collection is actually performed, one or more physiological parameter or biomarker sensing and recording abilities in combination with the physiological parameter or biomarker collection abilities such as, without limitation, cardio-data, including heart rate, electrocardiogram (ECG), and the like; respiration rate, temperature; pressure; chemical composition of fluid, e.g., analyte in blood, fluid state, blood flow rate, accelerometer motion data. The data can be stored in memory and when the biological sample collection device is sent to the processing facility 200 the data can be downloaded along with the biomarker.
Biological sample collection systems comprising receivers, configured with passive elements to collect physiological parameters or biomarkers for later analyses at a processing facility and a physiological data detection protocol when present in an active state, e.g., to obtain ECG data, accelerometer data, temperature data, will now be described in greater detail below.
Additionally, the receiver 901 may further include one or more distinct physiological parameter sensing abilities. By physiological parameter sensing ability is meant a capability of sensing a physiological parameter or biomarker, such as, but not limited to: heart rate, respiration rate, temperature, pressure, chemical composition of fluid, e.g., analyte detection in blood, fluid state, blood flow rate, accelerometer motion data, IEGM (intra cardiac electrogram) data.
In accordance with the teaching of the present disclosure, the receiver aspects of the receiver 901 may be configured to receive communications. The communications may be in the form of conductively modulated information communicated by any physiologic part of the body or from a device that communicates by way of conduction through a body using ionic emission through controlled release of mass from solid into a conducting solution or fluid. The communication may be produced by an ionic emission module or an IEM or a smart-parenteral delivery system. Ingestible event markers of interest include those described in PCT Application Serial No. PCT/US2006/016370 published as WO/2006/116718; PCT Application Serial No. PCT/US2007/082563 published as WO/2008/052136; PCT Application Serial No. PCT/US2007/024225 published as WO/2008/063626; PCT Application Serial No. PCT/US2007/022257 published as WO/2008/066617; PCT Application Serial No. PCT/US2008/052845 published as WO/2008/095183; PCT Application Serial No. PCT/US2008/053999 published as WO/2008/101107; PCT Application Serial No. PCT/US2008/056296 published as WO/2008/112577; PCT Application Serial No. PCT/US2008/056299 published as WO/2008/112578; and PCT Application Serial No. PCT/US2008/077753 published as WO 2009/042812; the disclosures of which applications are herein incorporated by reference. Smart parenteral delivery systems are described in PCT Application Serial No. PCT/US2007/015547 published as WO 2008/008281; each of the foregoing disclosures is herein incorporated by reference in its entirety.
As the receiver 901 of these aspects is configured to receive data encoded in current flow through a conductive fluid, the receiver 901 and the device that emits the communication (such as an IEM) use the living body with which they are associated as a communication medium. To employ the body as a communication medium, the body fluids act as the conducting fluid and the body of the subject is used as a conduction medium for communication. As such, the communication transferred between ionic emission device and any other emitting device and the receiver, such as the receiver 901, travels through the body of the subject 102. The conductively communicated information of interest may be communicated through and received from the skin and other body tissues of the subject body in the form of electrical alternating current (a.c.) communications that are conducted through the body tissues. As a result, such receivers do not require any additional cable or hard wire connection between the communicating device and the receiver.
As the receivers 901 are configured to receive conductively communicated information, they may include a transbody conductive communication module. The transbody conductive communication module is a functional module that is configured to receive a conductive communication, such as a communication emitted by an IEM. Where desired, the transbody conductive communication module may be implemented by a high power functional block. In some instances, the communication by the transbody conductive communication module is configured to receive is encoded information, by which is meant that the information has been modulated in some manner (for example using a protocol such as binary phase shift keying (BPSK), frequency shift keying (FSK), amplitude shift keying (ASK)). In such instances, the receivers and transbody conductive communication module thereof are configured to decode encoded information, such as information communicated by an IEM. The receivers may be configured to decode the encoded in a low signal to noise ratio (SNR) environment, e.g., where there may be substantial noise in addition to the information of interest, e.g., an environment having an SNR of 7.7 dB or less. The receivers may be further configured to decode the encoded information with substantially no error. In certain aspects, the receiver has a high coding gain, e.g., a coding gain ranging from 6 dB to 12 dB, such as a coding gain ranging from 8 dB to 10 dB, including a coding gain of 9 dB. The receivers of aspects disclosed herein can decode encoded information with substantially no error, e.g., with 10% error or less.
In those aspects where the received information is encoded, such as where the received information is an encoded IEM communication, the transbody conductive communication module may be configured to process the received communication with at least one demodulation protocol, where the transbody conductive communication module may be configured to process the received communication with two or more, three or more, four or more, different demodulation protocols, as desired. When two or more different demodulation protocols are employed to process a given encoded information, the protocols may be run simultaneously or sequentially, as desired. The received information may be processed using any convenient demodulation protocol. Demodulation protocols of interest include, but are not limited to: Costas Loop demodulation (for example, as described in PCT Application Serial No. PCT/US07/024,225 and published as WO 2008/063626, the disclosure of which is herein incorporated by reference); coherent demodulation (for example, as described in PCT Application Serial No. PCT/US07/024,225 and published as WO 2008/063626, the disclosure of which is herein incorporated by reference); accurate, low overhead iterative demodulation (for example, as described in PCT Application Serial No. PCT/US07/024,225 and published as WO 2008/063626, the disclosure of which is herein incorporated by reference); incoherent demodulation; and differential coherent demodulation.
In some instances, a coherent demodulation protocol is employed. Coherent demodulation modules that may be employed in aspects of the receivers include, but are not limited to, those described in PCT Application Serial No. PCT/US2007/024225; the disclosure of which is herein incorporated by reference.
In some instances, a differential coherent demodulation protocol is employed. Differentially coherent demodulation compares the phase of adjacent bits in a Binary phase-shift keying modulated communication (BPSK). For example an 8 bit binary code of 11001010 would result in a differential series of bits 0101111. Since the technique leverages phase differences between adjacent bits, it is inherently more robust against frequency instability and drift than a coherent demodulation scheme.
The body-associate biological sample collection devices and systems described herein (e.g., 100, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1400, 1500) of interest include both external and implantable devices. In external aspects, the biological sample collection device is ex vivo, by which is meant that the device is present outside of the body during use. Where the biological sample collection devices are external, they may be configured in any convenient manner, where in certain aspects they are configured to be associated with a desirable skin location. As such, in certain aspects the external biological sample collection devices are configured to be contacted with a topical skin location of a subject. Configurations of interest for the biological sample collection devices described herein (e.g., 100, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1400, 1500) include, but are not limited to: patches, wrist bands, jewelry (such as watches, earrings and bracelets), clothing, accessories, e.g., belts and shoes, eyeglasses. In some instances, the receivers are configured to adhere to a skin location, e.g., by use of suitable adhesive, such as described below. In some instances, the receivers are configured to touch a skin location but not adhere thereto, for example where the device is configured as a wrist band, an item of jewelry (such as a watch, an earring and a bracelet), an article of clothing, an accessory, such as a belt and a shoe, and a pair of eyeglasses. In yet other instances, the receivers may be configured to be maintained within some defined distance of a skin surface, such as within 1 cm, including within 0.5 cm.
In certain aspects, the biological sample collection devices and systems described herein (e.g., 100, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1400, 1500) are implantable components. By implantable is meant that the biological sample collection device is designed, i.e., configured, for implantation into a subject, e.g., on a semi-permanent or permanent basis.
In these aspects, the biological sample collection devices and systems described herein (e.g., 100, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1400) are in vivo during use. By implantable is meant that the biological sample collection device are configured to maintain functionality when present in a physiological environment, including a high salt, high humidity environment found inside of a body, for two or more days, such as about one week or longer, about four weeks or longer, about six months or longer, about one year or longer, e.g., about five years or longer. In certain aspects, the implantable biological sample collection devices are configured to maintain functionality when implanted at a physiological site for a period ranging from about one to about eighty years or longer, such as from about five to about seventy years or longer, and including for a period ranging from about ten to about fifty years or longer. For implantable aspects, the biological sample collection device may have any convenient shape, including but not limited to: capsule-shaped, disc-shaped. The biological sample collection device may be configured to be placed in a number of different locations, e.g., the abdomen, small of the back, shoulder (e.g., where implantable pulse generators are placed). In certain implantable aspects, the biological sample collection device is a standalone device, in that it is not physically connected to any other type of implantable device. In yet other aspects, the biological sample collection device may be physically coupled to a second implantable device, e.g., a device which serves as a platform for one or more physiological sensors, where the device may be a lead, such as a cardiovascular lead, where in certain of these aspects the cardiovascular lead includes one or more distinct physiological sensors, e.g., where the lead is a multi-sensor lead (MSL). Implantable devices of interest further include, but are not limited to: implantable pulse generators (e.g., ICDs), neurostimulator devices, implantable loop recorders.
The biological sample collection systems 900, 1000, 1100, 1400, 1500 may include a receiver element which serves to receive the conductive communication from the IEM. The receiver portion of the biological sample collection devices 900, 1000, 1100, 1400, 1500 may include a variety of different types of receiver elements, where the nature of the receiver element necessarily varies depending on the nature of the produced by the generation element. In certain aspects, the receiver element may include one or more electrodes for detecting communications from the generation element, such as two or more electrodes, three or more electrodes. In certain aspects, the receiver device will be provided with two or three electrodes that are dispersed at some distance from each other. This distance allows the electrodes to detect a differential voltage. The distance may vary, and in certain aspects ranges from 0.1 cm to 1.0 m, such as 0.1 to 5 cm, such as 0.5 to 2.5 cm, where the distance 1 cm in some instances.
The biological sample collection devices described herein may be able to collect environmental sample such as for air samples for mine workers or smog. So it is contemplated that any of the biological sample collection devices or systems 100, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1400, 1500 disclosed herein could be configured to sample both the environment as well the subject 102.
In term of size, any of the biological sample collection devices or systems 100, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1400, 1500 disclosed herein can be as small as a square centimeter and as large as 100 to 200 centimeters on a side. Accordingly, in various aspects, the size of the biological sample collection device may be range from about 1 cm to about 200 cm, for example.
Additional disclosure of receivers that may be employed in combination with the biological sample collection devices discussed herein is provided in U.S. patent application Ser. No. 12/673,326, titled “BODY-ASSOCIATED SIGNAL RECEIVER AND METHOD,” filed on Feb. 12, 2010, which is incorporated herein by reference in its entirety.
It is to be understood that this disclosure is not limited to particular aspects or aspects described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects or aspects only, and is not intended to be limiting, since the scope of the biological sample collection devices and systems is defined only by the appended claims.
Notwithstanding the claims, the invention is also defined by the following clauses:
1. A biological sample collection device, comprising:
a top cover plate;
a bottom portion attached to the top cover plate, the bottom portion comprising a remotely-analyzable biological sample collection portion to collect a biological sample from a body of a subject, wherein the biological sample is to be analyzed at a remote processing facility at a later time;
a fastening portion provided on the bottom portion to affix the remotely-analyzable biological sample collection device to the body of the subject;
2. The biological sample collection device of clause 1, comprising a real time clock coupled to the top cover plate.
3. The biological sample collection device of clause 2, comprising a memory coupled to the top cover plate and electrically coupled to the real time clock.
4. The biological sample collection device of clause 3, wherein the memory coupled to the real time clock is operative to time-stamp when the biological sample collection device is applied to the body of the subject
5. The biological sample collection device according to any of the preceding clauses wherein the remotely-analyzable biological collection portion comprises a sorbent material.
6. The biological sample collection device of clause 5, wherein the sorbent material comprises an adsorbent material or an absorbent material.
7. The biological sample collection device according to any of the preceding clauses wherein the remotely-analyzable biological collection portion comprises one or more of the following:
an adhesive material
at least one micro-needle.
a color indicator to indicate a presence or absence of a substance.
8. The biological sample collection according to any of the preceding clauses wherein the fastening portion comprises an adhesive material.
9. The biological sample collection device according to any of the preceding clauses further comprising:
at least two electrodes; and
an electronic module to extract fluids from the body of the subject via reverse electrophoresis and drive the biological sample from the body of the subject into the sample collection portion.
10. The biological sample collection device according to any of the preceding clauses further comprising a framework comprising a first and second dissimilar materials to generate an operational voltage when exposed to a conductive fluid when the biological collection device is applied to the body of the subject.
11. A biological sample collection system comprising a device according to any of the preceding clauses and further comprising:
a processing unit;
at least two electrodes coupled to the processing unit, the at least two electrodes configured to contact skin of a subject; and
a transbody conductive communication module coupled to the processing unit and the at least two electrodes, the transbody conductive communication module operative to detect and gather physiological information from the subject in the form of an electric current flow through the at least two electrodes at a first frequency, wherein the current flow at the first frequency is associated with a device associated with the subject.
12. The biological sample collection system of clause 11, further comprising:
a physiological sensing module coupled to the processing unit and the at least two electrodes, the physiological sensing module operative to sense physiological information from the subject in the form of electric current flow through the at least two electrodes at the second frequency, wherein the second frequency current flow is associated with the physiology of the subject.
13. The biological sample collection system of clause 11 or 12 further comprising:
a wireless communication module coupled to the processing unit operative to communicate information from the remotely-analyzable biological collection device to a communication device external to the subject.
14. The biological sample collection system according to any of the clauses 11-13 wherein the transbody conductive communication module is configured to receive communications from an ingestible event marker located inside the body of the subject.
15. The biological sample collection system according to any of the clauses 12-14 wherein the physiological sensing module is configured to receive communications from a device embedded in the body of the subject.
16. The biological sample collection system according to any of the clauses 13-15 wherein the wireless communication module is configured to communicate data obtained from the ingestible event marker, and/or wherein the wireless communication module is configured to receive data providing for subject directed permissions.
17. Use of a device and/or a system according to any of the preceding clauses for obtaining and/or transmitting physiological information from and/or to a subject
Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the present disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the present disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits also are included in the present disclosure.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the apparatuses, systems, and methods described in the present disclosure, representative illustrative methods and materials are now described.
All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of priority. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.
It is noted that, as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as solely, only and the like in connection with the recitation of claim elements, or use of a negative limitation.
As will be apparent to those of skill in the art upon reading the present disclosure, each of the individual aspects and aspects described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several aspects without departing from the scope of the present disclosure. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.
Although the foregoing disclosure has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this disclosure that certain changes and modifications may be made thereto without departing from the scope of the appended claims.
Accordingly, it will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the present disclosure and are included within its scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles described in the present disclosure and the concepts contributed to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and aspects as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. The scope of the present disclosure, therefore, is not intended to be limited to the exemplary aspects and aspects shown and described herein. Rather, the scope of present disclosure is embodied by the appended claims.
It is worthy to note that any reference to “one aspect” or “an aspect” means that a particular feature, structure, or characteristic described in connection with the aspect is included in at least one aspect. Thus, appearances of the phrases “in one aspect” or “in an aspect” in various places throughout the specification are not necessarily all referring to the same aspect. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner in one or more aspects.
Some aspects may be described using the expression “coupled” and “connected” along with their derivatives. It should be understood that these terms are not intended as synonyms for each other. For example, some aspects may be described using the term “connected” to indicate that two or more elements are in direct physical or electrical contact with each other. In another example, some aspects may be described using the term “coupled” to indicate that two or more elements are in direct physical or electrical contact. The term “coupled,” however, also may mean that two or more elements are not in direct contact with each other, but yet still co-operate or interact with each other.
While certain features of the aspects have been illustrated as described herein, many modifications, substitutions, changes and equivalents will now occur to those skilled in the art. It is therefore to be understood that the appended claims are intended to cover all such modifications and changes as fall within the scope of the present disclosure.
This application claims the benefit of U.S. Provisional Patent Application No. 61/451,934 entitled “Biological Sample Collection Device and System” and filed on Mar. 11, 2011, which is herein entirely incorporated by reference.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US2012/028342 | 3/8/2012 | WO | 00 | 11/18/2013 |
| Number | Date | Country | |
|---|---|---|---|
| 61451934 | Mar 2011 | US |
