Abstract: A multi-needle injection system having a collapsible and expandable frame portion is provided. The system can be adapted for delivery trans-urethrally into the bladder, and expanded to touch or penetrate a wall portion of the bladder. A plurality of positioned needles can inject at multiple points into the bladder wall simultaneously to introduce a therapeutic or treatment substance.

Abstract: A catheter-based/intravascular fluid injection system with application to renal denervation includes a multiplicity of needles which expand open around a central axis to engage the wall of a blood vessel, or the wall of the left atrium, allowing the injection of a cytotoxic and/or neurotoxic solution for ablating conducting tissue, or nerve fibers around the ostium of the pulmonary vein, or circumferentially in or just beyond the outer layer of the renal artery. The expandable delivery system includes expandable components that facilitate positioning of a multiplicity of injection needles against the inside wall of a blood vessel from where they can be advanced. The system also includes means to limit and/or adjust the depth of penetration of the ablative fluid into the tissue of the wall of the targeted blood vessel.

Abstract: A liquid delivery apparatus for the intrathecal delivery of one or more medications to a patient is disclosed. The liquid delivery apparatus generally includes a liquid reservoir, a liquid metering unit fluidly connected to the liquid reservoir, and a catheter delivery tube fluidly connected to the liquid metering unit. Preferably, the liquid delivery apparatus includes two or more liquid reservoirs. In various embodiments, the liquid reservoir includes a deformable balloon and a compressive sleeve spring as a pressure source, the liquid metering unit is a piezoelectrically actuated microvalve, and/or diagnostic sensors are included in the apparatus. The disclosed apparatus are compact, volume-efficient, energy-efficient, capable of delivering accurate fluid volumes, and address problems associated with multi-medication therapies. Methods of operating the liquid delivery apparatus are also disclosed.

Abstract: A built-in non-verbal compact instructional device integratable to an applicator having a microdevice for painlessly perforating skin and optionally an active agent for application to the perforated area. The microdevice can include microneedles, microneedle arrays, microblades, microblade arrays, microknives, microknife arrays, and Functional MicroArrays (FMAs). The active agent can be stored in a first chamber. The microdevice can perforate stratum corneum without significant pain or discomfort to a patient. The active agent is applied to the perforated area. The device verifies compliance with predetermined methods of use, such as a light to indicate application with the recommended amount of force for perforating skin. The applicator can provide enhanced delivery of an active agent, with minimal discomfort, for therapeutic or cosmetic treatment, such as topical treatment for acne, or other skin disorders, wrinkles, blemishes, etc.

Abstract: The methods, systems, and devices disclosed herein generally involve convection-enhanced delivery of drugs to a target region within a patient. Microfluidic catheter devices are disclosed that are particularly suitable for targeted delivery of drugs via convection, including devices capable of multi-directional drug delivery, devices that control fluid pressure and velocity using the venturi effect, and devices that include conformable balloons. Methods of treating various diseases using such devices are also disclosed, including methods of treating cerebral and spinal cavernous malformations, cavernomas, and hemangiomas, methods of treating neurological diseases, methods of treatment using multiple microfluidic delivery devices, methods of treating hearing disorders, methods of spinal drug delivery using microfluidic devices, and methods of delivering stem cells and therapeutics during fetal surgery. Methods of manufacturing such devices are also disclosed.

Abstract: The methods, systems, and devices disclosed herein generally involve convection-enhanced delivery of drugs to a target region within a patient. Microfluidic catheter devices are disclosed that are particularly suitable for targeted delivery of drugs via convection, including devices capable of multi-directional drug delivery, devices that control fluid pressure and velocity using the venturi effect, and devices that include conformable balloons. Methods of treating various diseases using such devices are also disclosed, including methods of treating cerebral and spinal cavernous malformations, cavernomas, and hemangiomas, methods of treating neurological diseases, methods of treatment using multiple microfluidic delivery devices, methods of treating hearing disorders, methods of spinal drug delivery using microfluidic devices, and methods of delivering stem cells and therapeutics during fetal surgery. Methods of manufacturing such devices are also disclosed.

Abstract: The methods, systems, and devices disclosed herein generally involve convection-enhanced delivery of drugs to a target region within a patient. Microfluidic catheter devices are disclosed that are particularly suitable for targeted delivery of drugs via convection, including devices capable of multi-directional drug delivery, devices that control fluid pressure and velocity using the venturi effect, and devices that include conformable balloons. Methods of treating various diseases using such devices are also disclosed, including methods of treating cerebral and spinal cavernous malformations, cavernomas, and hemangiomas, methods of treating neurological diseases, methods of treatment using multiple microfluidic delivery devices, methods of treating hearing disorders, methods of spinal drug delivery using microfluidic devices, and methods of delivering stem cells and therapeutics during fetal surgery. Methods of manufacturing such devices are also disclosed.

Abstract: An apparatus for performing phlebotomy through a peripheral intravenous line is described herein. The apparatus includes an introducer and a cannula and is configured to advance the cannula through a peripheral intravenous line. A y-adapter with a port of larger diameter is configured to receive the cannula to place the cannula in fluid communication with the peripheral intravenous line. When advanced, the cannula is configured to transport a bodily fluid to a volume outside of the body.

Abstract: The present invention provides for transdermal delivery devices having microneedle arrays, as well as methods for their manufacture and use. In one embodiment, a transdermal delivery device is provided. The transdermal delivery device includes a polymer layer which has microneedles projecting from one of its surfaces. The microneedles are compositionally homogenous with the polymer base layer.

Abstract: A method of manufacturing a microneedle including forming a plurality of first linear grooves on a substrate in parallel to one another along a first direction using grinding and forming a plurality of second linear grooves on the substrate in parallel to one another in a second direction intersecting the first direction using grinding. At least one of the forming of a plurality of first linear grooves and the forming of a plurality of second linear grooves includes forming first stage grooves using a first dicing blade; and processing the first stage grooves by tracing the first stage grooves using a second dicing blade having a side surface different from that of the first dicing blade to thereby form second stage grooves.

Abstract: Disclosed herein are apparatus and techniques for applying a device to a subject. Such apparatus and techniques may provide feedback to an operator and/or regulate the force used to apply the device, yielding an improved result. Particularly useful embodiments include apparatus and techniques for applying a medical device, such as a skin surface electrode or microneedle array, to a patient's tissue.

Abstract: An object of the present invention is to provide a novel microneedle array that has (1) the strength to withstand insertion into the skin surface layer and/or stratum corneum, (2) the fineness and flexibility to cause no pain or bleeding in the skin surface layer and/or stratum corneum at the insertion site of the microneedles, and (3) solubility or biodegradability of the microneedle portions under the skin. [Method for Achieving the Object] The microneedle array is produced by forming microneedles using proteoglycan as a base material.

Abstract: A needle device for the delivery of therapeutic material into tissue comprising a connection to a pressure generation element, a lumen adapted for the passage of a therapeutic material, and a needle barrel, wherein each needle barrel comprises an opening adapted to control and deliver a pressure transmitted from the pressure generation element into a tissue to cause an increase in the permeability of a cell membrane to the therapeutic material.

Abstract: The present invention provides compositions, devices, methods and processes related to the intradermal delivery of PTHrP and PTHrP analogues, particularly [Glu22,25, Leu23,28,31, Aib29, Lys26,30]hPTHrP(1-34)NH2.

Abstract: A drug delivery device (100) for administering a low dose of a medicament includes a housing (111) and a drug reservoir (101) disposed in the housing (111). A needle (135) is connected to the drug reservoir (101). A pressure applying member (113) is movably connected to the housing (111) and is movable between first and second positions. The pressure applying member (113) does not apply pressure to the drug reservoir (101) in the first position and applies pressure to the drug reservoir (101) in the second position to dispense medicament stored in the drug reservoir (101). A method of administering a low dose of insulin to simulate a first-phase insulin response of a pancreas is also disclosed.

Abstract: An applicator used to apply microneedle arrays to a mammal In particular, an application device for applying a microneedle device to a skin surface comprising a flexible sheet having a raised central area attached to the microneedle device and a supporting member at or near the periphery of the flexible sheet, wherein the flexible sheet is configured such that it will undergo a stepwise motion in the direction orthogonal to the major plane of the sheet.

Abstract: An apparatus that includes two syringes, or a “double barrel syringe,” includes one syringe that injects or infuses while the other syringe aspirates. In the double barrel syringe, injection and aspiration may be effected by a single action. The double barrel syringe may include a handle with two members. A first member of such a handle includes one arm that pivotally couples to a plunger of a first syringe and another arm that pivotally couples to a barrel of a second syringe. A second member of the handle includes one arm that pivotally couples to a barrel of the first syringe and another arm that pivotally couples to a plunger of the second syringe. Methods for injecting or infusing simultaneously with aspirating are also disclosed.

Abstract: The present invention includes a microneedle assembly having a support that includes a first surface and a second surface, the second surface further including a slanted surface. A plurality of microneedles are provided which project outwardly from the second surface of the support. A pathway through the microneedle assembly is formed and includes an aperture extending between the first surface of the support and the second surface of the support, a channel disposed on the exterior surface of at least one microneedle, the channel having a surface, the channel being in alignment with at least a portion of the aperture to form a junction through which fluids may pass.

Abstract: A dermal delivery apparatus includes a pad having a surface to interface with an outer layer of skin. The dermal delivery apparatus also includes a micro structure coupled to the pad and configured to penetrate and deliver an agent beneath the outer layer of skin. The dermal delivery device also includes a base at least partially surrounding the micro structure. The base is coupled to the pad and protrudes away from the surface of the pad to apply surface tension to the skin.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of liquid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: Embodiments disclosed herein are directed to systems and methods for automatically inserting a needle into an insertion-target region of a living subject in response to a machine-vision system locating the insertion-target region. In an embodiment, a needle insertion system includes a moveable needle configured to be inserted into a living subject, a machine-vision system configured to locate an insertion-target region of the living subject, control electrical circuitry, and an actuator coupled to the control electrical circuitry. The control electrical circuitry may be coupled to the machine-vision system to receive location information therefrom about the insertion-target region, and configured to output needle targeting instructions. The actuator may be coupled to the control electrical circuitry to receive the needle targeting instructions therefrom and coupled to the moveable needle.

Abstract: A microneedle device having a coating including a high molecular weight pharmaceutical compound substantially uniformly is provided. A microneedle device (1) includes a plurality of microneedles (3) on a microneedle substrate (2), which are capable of piercing the skin. A portion of or entire surface of the microneedles (3) and/or the microneedle substrate (2) has a coating including a coating carrier in a solid state. The coating carrier includes a high molecular weight pharmaceutical compound and polysaccharides compatible with the high molecular weight pharmaceutical compound. Herein, as the polysaccharide, for example, pullulan or hydroxypropylcellulose can be used.

Abstract: A method and device to deliver medication in a liquid, gel or suspension formulation to a plurality of adjacent tissue sites of a mammal, the device comprising a plurality of tissue-engaging members for receiving the medication and operably engageable with the plurality of tissue sites; means for supplying the tissue-engaging members with the formulation, and to temporarily sustain and control the rate of therapeutic agent/unit of time and preferably to sustain these controlled delivery rates over extended periods of time to enhance the local therapeutic effect of these therapeutic agents and to reduce the systemic toxicity and reduce unwanted side effects.

Abstract: A medical device is provided. The device includes a cannula with a lumen and a plurality of apertures and a visually perceptible indicator that is configured to allow the cannula to be positioned at an appropriate rotational position within the patient. A plurality of injection needles are disposed within the lumen and a first handle is fixed with respect to the cannula and a second handle is disposed in conjunction with the first handle and fixed to the proximal portion of each of the plurality of needles, the first handle is translatable with respect to the second handle to translate the plurality of needles from a first position where the distal portions of each of the plurality of needles are disposed within the lumen of the cannula, and a second position where the distal portion of each of the plurality of needles extends out of the lumen through their respective aperture.

Abstract: An insertion device and insertion set. The insertion device for inserting at least a portion of at least one piercing member of an insertion set through the skin of a patient includes a device housing, a carrier body and a driver. The carrier body is slidably received within the device housing for movement between an advanced position and a retracted position. The carrier body also includes a receiving structure to support the insertion set in a position with the at least one piercing member oriented for insertion through the skin of the patient at a predetermined or variable angle relative to the skin of the patient upon movement of the carrier body from the retracted position to the advanced position.

Abstract: Microneedle comprising a distal part made of a soluble material, characterized by the fact that said distal part comrises a skeleton.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of liquid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: A manifold has at least one manifold aperture extending therethrough and selectively placed in fluid communication with a fluid source. An insertion structure has at least one interior cavity at least partially defined by a structure shell and is selectively placed in fluid communication with a corresponding manifold aperture. The insertion structure is configured for selective placement in a penetrating relationship with a patient tissue below a surface of the patient tissue. At least one shell perforation extends through the structure shell and places the interior cavity in fluid communication with a surrounding ambient space. At least one fluid path extends from the fluid source, through the manifold aperture, into the interior cavity, through at least one shell perforation, and at least one of a proximate relationship and a contacting relationship with the patient tissue beneath the outer surface thereof. A fluid is directed along the fluid path.

Abstract: The invention relates to an arrangement for delivering a fluid medicament, the arrangement comprising a medicament container that comprises an array of separated reservoirs. Each reservoir comprises a defined charge of a fluid medicament and is separately dischargeable. The reservoirs are flexible and connected by a connecting element. The arrangement further comprises a dosage apparatus comprising a releasing actor designed to activate the release of the charge of fluid medicament from a reservoir to a needle. The dosage apparatus comprises a transportation arrangement designed to provide the releasing actor with reservoirs to be released, or designed to move the releasing actor to a reservoir to be released next.

Abstract: Systems and methods for delivering and infusing formulations containing riboflavin or its analogues, or other ophthalmic formulations, into corneal tissue are disclosed. Systems and methods are further disclosed to cross-link the corneal tissue through exposure to UVA irradiation. The systems and methods for formulation delivery employ micro-needle array delivery devices.

Abstract: The present invention provides an electrospray device using a high frequency alternating current (AC) above 10 kHz to generate fine micron sized drops. The apparatus generally functions by applying a high frequency alternating current electric field across one or more micro-needles and one or more conducting elements. The present invention may be used to generate aerosol drops for respiratory drug delivery or as a microencapsulation technique for the encapsulation of drugs, DNA, protein, osteogenic or dermatological growth factors, bacteria, viruses, immobilized enzyme receptors and fluorescent particles for controlled release drug delivery, tissue or bone engineering, clinical or environmental field testing and as biosensors for clinical or drug monitoring. In addition, the present invention may be used to synthesize biodegradable fibers as bioscaffolds for tissue engineering, surgical sutures or medical gauze that enhance blood coagulation, and further may be encapsulated by other agents.

Abstract: Methods and devices are provided for targeted administration of a drug to a patient's eye. In one embodiment, the method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. The fluid drug formulation may flow circumferentially toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye.

Abstract: A transcutaneous multimodal delivery device for drug delivery and the methods of making and using the same are provided.

Abstract: A transdermal patch that can easily deliver a controlled volume of a fluidic drug compound to the skin is provided. More particularly, the patch contains a microneedle assembly that is configured to be placed in fluid communication with a drug delivery assembly. The microneedle assembly contains a support and a plurality of microneedles that extend outwardly from the support. The microneedles are formed with one or more channels of a certain dimension such that passive capillary flow drives the flow of the drug compound. The drug delivery system contains a reservoir for the drug compound that is in fluid communication with a rate control membrane that helps control the flow rate of the drug compound by modulating its pressure downstream from the reservoir. A release member is also positioned adjacent to the microneedle and drug delivery assemblies. Prior to use, the release member acts as a barrier to the flow of the drug compound and thus inhibits premature leakage.

Abstract: A transdermal transport device includes a reservoir for holding a formulation of an active principle, and a needle with a bore extending along the length of the needle from a first end of the needle to a second end of the needle. The second end is substantially aligned to a plane parallel to a body surface of a biological body when the device is placed on the body surface. The device also includes an actuator which pumps the formulation through the bore of the needle between a target area of the body and the reservoir.

Abstract: A method and apparatus for application of a microneedle patch to a skin surface of a patient includes use of an applicator. The applicator includes a housing, a slidably disposed applicator plate, and a compression spring. The applicator plate is moveable between a retracted position and a deployed position, and has an engaging surface suitable for mashing up against a microneedle patch and pressing it against a skin surface. A docking system transfers the microneedle patch from a support to the applicator without requiring a user to handle the microneedle patch directly. Once mounted in the applicator, the microneedle patch is deployed against a skin surface of a patient for delivery of a desired agent via a microneedle array contained on the patch.

Abstract: An injection device is provided. The device includes a housing having a first end defining a first opening. A plunger is received within the first opening of the housing to move between first and second positions. A cartridge is disposed in the housing and has an interior serving as a reservoir for a drug. A delivery needle is disposed within the housing and is in fluid communication with the reservoir via an interruptible fluid channel. A locking mechanism is disposed in the housing. In the first position of the plunger the delivery needle is enclosed by the plunger and in the second position of the plunger the delivery needle is placed in an injection position and the plunger activates the locking mechanism whereby when the plunger returns to the first position the .locking mechanism prevents the needle from being placed in the injection position.

Abstract: An evacuation sheath assembly and method of reducing or removing a blockage within a vessel without permitting embolization of particulate matter is provided. The evacuation sheath assembly includes a first elongate tubular member, having proximal and distal ends and a main lumen configured to be placed in fluid communication with a blood vessel. An expandable member is provided on a distal portion of the tubular member and is configured to form a seal with the blood vessel. The evacuation assembly further includes a second elongate tubular member having proximal and distal ends and an inflation lumen configured to be placed in fluid communication with the expandable member and a gas inflator. The gas inflator includes a high pressure gas source and a mechanism for regulating the pressure of the gas delivered by the gas inflator.

Abstract: An improved method and apparatus is provided as a system to deliver a composition, preferably a medical or pharmaceutical composition or active, through the stratum corneum of skin, without introducing bleeding or damage to tissue, and absent pain or other trauma. The dimensions and shapes of the microelements are controlled so as to control the penetration depth into the skin. The microelements can be “hollow” such that passageways are created therethrough to allow the composition to flow from a chamber, through the microelements, and into the skin. Alternatively, the microelements can be “solid,” and the composition is applied directly to the skin just before or just after the microelements are applied to the skin surface to create the openings in the stratum corneum.

Abstract: The present invention provides for microneedle arrays and related systems and methods. Particularly, microneedle arrays that are configured to deliver active agents, including nucleic acids and vaccines, are provided. Additional related methods of vaccinating and minimizing the amount of vaccine necessary for effective inoculation are also provided.

Abstract: In an aspect of the invention, serotonin receptor antagonist formulations are provided for subcutaneous, transdermal or intradermal delivery to a subject. In an embodiment, serotonin receptor antagonist formulations include ondansetron or ondansetron-containing formulations. In another embodiment, serotonin receptor antagonist formulations include palonosetron or palonosetron-containing formulations. In another aspect of the invention, microinjection devices are provided for delivering a serotonin receptor antagonist formulation to a subject.

Abstract: Relations between crystallinity and performance of a biodegradable resin, between weight-average molecular weight and strength thereof, and between weight-average molecular weight and performance thereof were clarified. As a result thereof, when a microneedle array was provided with microneedles containing noncrystalline polylactic acid which had a weight-average molecular weight of 40,000 to 100,000, it was possible to obtain a microneedle array which could maintain its functional performance.

Abstract: A cartridge with injection needles for an injection device. The cartridge includes a plurality of injection needle assemblies, each including a hub, mounted to be shiftable in cavities of a needle assembly support. A hub ledge having a drive member engageable push surface projects within a gap between a first hub portion and a second hub portion. Driving engagement of the push surface by an injection device drive member shifts the needle assembly from a retracted position to an injection position, during which shifting the second hub portion moves relative to the first hub portion. A pull surface on the second hub portion is engagable with the drive member for lifting the needle assembly from the injection position.

Abstract: A method and system is disclosed for operating a medical device with or without a cassette in place. A method is disclosed for adding additional VTBI to an ongoing infusion without stopping the infusion and with maintaining the infusion parameters. A method and system is disclosed for changing the CCA without having to interrupt or completely stop an ongoing infusion. Quick titration buttons are provided to allow improved navigation between various delivery display screens.

Abstract: The invention relates to a microneedle drug monitoring system, and also a microneedle device when provided with the drug monitoring system, comprising the selective and sequential coating of microneedles with layers of indicator material and therapeutic agent.

Abstract: A transdermal patch can include a drug source, a porator, and an energy storage device on-board the patch. Conductive contact terminals can extend from the energy storage device for connection to an external source of power. The porator operates free of any concurrent connection to any external source of power. A switch can be used to make the selective electrical connection between the porator and the energy storage device. The switch can be arranged to respond to a manual user action after the patch has been adhered to skin, including separation of the porator from a remainder of the patch. Optionally, a series of switches can make electrical connections between the porator and respective individual energy storage devices. In another aspect, a transdermal patch includes a mechanical bias that applies a displacement force to the porator to thereby better ensure good physical contact between the porator and the skin.

Abstract: A transdermal fluid delivery device includes a housing defining a longitudinal axis and having a proximal end and a distal end. The housing defines a passageway extending longitudinally therethrough. A fluid reservoir is disposed at the proximal end of the housing in communication with the passageway of the housing and is adapted for retaining a fluid therein. A base member is positioned at the distal end of the housing. A microneedle assembly including a plurality of microneedles extending distally therefrom is also provided. The microneedle assembly is selectively moveable with respect to the housing between a retracted position, wherein the microneedles are disposed within the housing, and an extended position, wherein the microneedles are advanced distally to penetrate the base member and extend distally therefrom for puncturing the patient's epidermis and delivering the fluid into the patient's bloodstream.

Abstract: The transdermal administration device of the present invention includes: a needle support with a plurality of microneedles formed at a tip portion thereof; a holder with the needle support placed therein, allowing the needle support to protrude itself therefrom and retract therein; and a cap for covering the microneedles, and further includes: a spring member placed between the needle support and the holder, for biasing the needle support in a protruding direction; an engaging portion at a base of the needle support; and an engaged portion capable of engaging the engaging portion, formed in the holder, where the engaging portion of the needle support can be locked with the engaged portion of the holder when the needle support is retracted in the holder.

Abstract: A drug delivery device is provided. The drug delivery device includes a drug reservoir in fluid communication with a microneedle array. The drug delivery device has a sliding actuation mechanism that may be activated by a button or lever. Actuation of the drug delivery device inserts the microneedle array into the skin of a subject and causes a piston to compress the drug reservoir, thereby delivering the drug through the microneedle array to the subject.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.