Abstract: The present disclosure provides improved methods for bead beating and a bead beating system useful therefor. The present disclosure further provides methods of using the bead beating system to extract nucleic acids from cells containing the nucleic acids.

Abstract: An apparatus produces a target metabolite in a bioreaction. The apparatus has a reactor vessel that contains a bulk liquor in which the bioreaction is conducted, with a headspace provided above the bulk liquor. In some instances, the target metabolite is favorably partitioned into a foam formed at an interface of the bulk liquor and the headspace. A foam collector is arranged to receive this foam from the bioreactor and break it into a condensed foam liquid, from which the target metabolite may be isolated and purified. In one exemplary application, paenibacillin is produced by fermentation of a medium by Paenibacillus polymyxa OSY-DF, and is preferentially concentrated in the foam. In another exemplary application, fermentation of a medium by Bacillus velezensis GF610 produces amyloliquecidin GF610 is which is preferentially concentrated in the foam.

Abstract: The present disclosure describes a computer implemented method, a system, and a computer program product of controlling the purification of a macromolecule solution via real-time multi-angle light scattering.

Abstract: A dynamic impedance imaging system includes a dynamic impedance imaging sensor, an impedance detection and flow rate measurement module and an electrical impedance tomography (EIT) instrument. The impedance detection and flow rate measurement module is configured to detect an abnormal particle flowing through the dynamic impedance imaging sensor to obtain a flow rate of the abnormal particle, and generate a synchronous trigger signal. The EIT instrument is configured to inject a sinusoidal excitation current into the dynamic impedance imaging sensor under the trigger of the synchronous trigger signal, perform multi-channel interleaved sampling for the abnormal particle according to the flow rate to acquire multi-channel sampled data, and calibrate the multi-channel sampled data to implement impedance tomography imaging for the abnormal particle.

Abstract: Nanosecond pulsed electric field (nsPEF) treatments of a tumor are adjusted based on a size and type of the tumor to stimulate an immune response against the tumor and other tumors in the subject. Calreticulin expression on tumor cells can be detected to confirm treatment. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated by directly treating a tumor that is most accessible. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and/or strength of tumors and/or a quantity of tumors in the subject.

Abstract: A method for separating a nucleic acid from a specimen includes accommodating a specimen in an accommodation space provided in a nucleic acid-collecting member, transferring a treatment reagent to the nucleic acid-collecting member by connecting a treatment reagent-accommodating container to a treatment reagent-supplying opening of the nucleic acid-collecting member, obtaining a mixture by mixing the specimen and the treatment reagent in a mixing space formed by combining an inner container space of the treatment reagent-accommodating container and the accommodation space of the nucleic acid-collecting member, and pressure-feeding the mixture by reducing a volume of the inner container space of the treatment reagent-accommodating container and discharging the mixture from an mixture-discharging opening of the nucleic acid-collecting member via a carrier that adsorbs the nucleic acid released in the mixture while allowing the mixture to permeate therethrough.

Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: Nanosecond pulsed electric field (nsPEF) treatments of a tumor are adjusted based on a size and type of the tumor to stimulate an immune response against the tumor and other tumors in the subject. Calreticulin expression on tumor cells can be detected to confirm treatment. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated by directly treating a tumor that is most accessible. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and/or strength of tumors and/or a quantity of tumors in the subject.

Abstract: A biological sample processing device includes a base, a purification unit, a metering unit and a first tube. The purification unit is disposed on the base and is configured to purify a sample. The metering unit is disposed on the base and has an inlet, at least one metering trough and an overflow trough. The inlet is connected to the purification unit via the first tube, and the metering trough is connected between the inlet and the overflow trough. The sample from the purification unit is configured to enter the metering unit through the inlet to be moved toward the metering trough, and to be moved toward the overflow trough after the metering trough is filled with the sample.

Abstract: Bioreactors and methods for cultivating microalgae under heterotrophic growth conditions using fruit wastewater as a carbon source are provided herein. The heterotrophic growth conditions include low irradiance of light sufficient to initiate light-activated metabolism, but not photosynthesis. The methods provide a cost effective and environmentally friendly solution for converting wastewater from dried fruit and wine industries into products like biofuels.

Abstract: Nanosecond pulsed electric field (nsPEF) treatments of a tumor are adjusted based on a size and type of the tumor to stimulate an immune response against the tumor and other tumors in the subject. Calreticulin expression on tumor cells can be detected to confirm treatment. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated by directly treating a tumor that is most accessible. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and/or strength of tumors and/or a quantity of tumors in the subject.

Abstract: An apparatus for generating one or several droplets of a first liquid in a second liquid immiscible with the first liquid includes a rotational body and a drive apparatus. The rotational body includes a fluid chamber, a fluid channel and a transition area. The transition area includes a first expansion area and a second expansion area. The drive apparatus is configured to provide the rotational body with such a rotation that the first liquid is supplied centrifugally to the fluid chamber and that centrifugally hydrodynamically induced pressure and lifting forces are caused due to the second expansion area, which cause a droplet break-off in the first liquid, such that a droplet of the first liquid embedded in the second liquid is generated.

Abstract: An apparatus for analyzing individual cell composition in a heterogeneous cell population may include, in one embodiment, a deposition plate having an array of microwells disposed therein, and a cover plate substantially overlying the deposition plate. A pair of electrodes may be associated with one or more of the microwells, and may be configured to generate an electric field within the associated microwell.

Abstract: An apparatus for destroying cancer cells in blood includes a vessel for accepting a flow of blood of a patient through the vessel, and a sound energy source coupled with the vessel for generating sound energy at a resonant sweep frequency that causes cancer cells, within the flow of blood in the vessel, to act as cavitation nuclei and implode without implosion of other cells not resonant with the resonant sweep frequency. A method for destroying cancer cells in blood includes circulating blood from a patient through a vessel coupled with a sound energy source and exposing the blood, when passing through the vessel, to sound energy at a resonant sweep frequency to make cancer cells therein act as cavitation nuclei and implode without implosion of other cells not resonant with the resonant sweep frequency.

Abstract: A subject is inoculated from a disease by exposing a biopsy of a tumor or other abnormal growth to a nanosecond pulsed electric field (nsPEF). A sufficient treatment can be confirmed by detecting calreticulin on the tumor cell membranes, which indicates apoptosis occurring in the tumor cells. Treated tumor cells from the biopsy are then reintroduced into the subject. The calreticulin-exhibiting tumor cells activate the subject's immune system against the tumor, and any other like tumors in the body, and effectively vaccinates the subject against the disease. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. The immune response may be measured at a later time. Specific electrical characteristics of the nsPEF treatments can be based on the type and/or strength of the tumor.

Abstract: A micro-electro-mechanical system for heating a sample including a substrate, a micro-channel flow channel in the substrate, a carrier fluid within the micro-channel flow channel for moving the sample in the micro-channel flow channel, and a microwave source that directs microwaves onto the sample in the micro-channel flow channel for heating the sample. The carrier fluid and the substrate are made of materials that are not appreciably heated by the microwaves. The microwave source includes conductive traces or strips and a microwave power source connected to the conductive traces or strips.

Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: Method and apparatus for controlling acoustic treatment of a sample including a liquid. A processing volume in which the sample is acoustically treated may be controlled, e.g., by positioning a suitable element so as to reduce and/or eliminate a headspace size at a sample/gas interface. An interaction between the acoustic energy and the sample may be controlled, e.g., by using a headspace control element positioned at least partially in the sample that helps to reduce splashing or other sample ejection that would otherwise occur.

Abstract: Methods are disclosed for separating beads and cells from a host fluid. The method includes flowing a mixture containing the host fluid, the beads, and the cells through an acoustophoretic device having an ultrasonic transducer including a piezoelectric material driven by a drive signal to create a multi-dimensional acoustic standing wave. A drive signal is sent to drive the at least one ultrasonic transducer to create the multi-dimensional acoustic standing wave. A recirculating fluid stream having a tangential flow path is located substantially tangential to the standing wave and separated therefrom by an interface region. A portion of the cells pass through the standing wave, and the beads are held back from the standing wave in the recirculating fluid stream at the interface region. Also disclosed is an acoustophoretic device having a coolant inlet adapted to permit the ingress of a cooling fluid into the device for cooling the transducer.

Abstract: Nanosecond pulsed electric field (nsPEF) treatments of a tumor are adjusted based on size and type of a tumor to stimulate an immune response against the tumor and other tumors in a subject. Calreticulin expression on tumor cells can be detected to confirm treatment. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated by directly treating a tumor that is most accessible. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and/or strength of tumors and/or a quantity of tumors in the subject.

Abstract: Method and apparatus for controlling acoustic treatment of a sample including a liquid. A processing volume in which the sample is acoustically treated may be controlled, e.g., by using a bead positioned in the sample that helps to enhance the shearing effects of acoustic energy on genomic fragments.

Abstract: Methods for a new, drug-free therapy for treating solid skin tumors through the application of nanosecond pulsed electric fields (“nsPEFs”) are provided. In one embodiment of the invention, the cells are melanoma cells, and the applied nsPEFs penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin.

Abstract: Nanosecond pulsed electric field (nsPEF) treatments of a tumor are used to cause the tumor to express calreticulin and stimulate an immune response against the tumor and other tumors in a subject. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and/or strength of tumors and/or a quantity of tumors in the subject.

Abstract: The present invention discloses a system for testing microfluid which is made with a disposable disc. The high sensitivity, high sensing accuracy, and quick response microfluidic disc is demonstrated in the present invention. It is note that easy to test microfluid without traditional detecting method, and then reduce energy and simplify procedure. Furthermore, to additive the microfluidic disc is useful to enhance blood typing, and hence raising the sensitivity by the video recognition of blood agglutination.

Abstract: A fluid controlling apparatus including an inlet through which a fluid is introduced, a channel portion connected to the inlet, an outlet that is connected to the channel portion and through which the fluid is discharged, and at least one fluid resisting portion disposed between the inlet and the outlet, as well as a filter and a biochip including the fluid controlling apparatus.

Abstract: Embodiments of the disclosure relate to platelet activation and/or aggregation using electric pulses. In one embodiment, a platelet-containing sample is exposed to electric pulses. At least one of the electric pulses has a duration greater than 1 microsecond and a field strength below 50 kV/cm. In another embodiment, the electric pulses may be designed with particular field strengths and durations.

Abstract: A method for digesting biological cells in a reaction container includes treating the cells with pressure pulses. The pressure pulses are generated by at least one eddy current actuator in conjunction with an electric conductor arranged on or in the reaction container.

Abstract: Method and apparatus for controlling acoustic treatment of a sample including a liquid. A processing volume in which the sample is acoustically treated may be controlled, e.g., by positioning a suitable element so as to reduce and/or eliminate a headspace size at a sample/gas interface. An interaction between the acoustic energy and the sample may be controlled, e.g., by using a headspace control element positioned at least partially in the sample that helps to reduce splashing or other sample ejection that would otherwise occur.

Abstract: Methods and systems for treating material with focused acoustic energy and/or ultraviolet radiation are described. Sample material may be provided to a single batch vessel or may flow in a continuous or intermittent fashion into/out of a processing chamber within which the material is exposed to focused acoustic energy and/or ultraviolet radiation. Exposure to focused acoustics in a flow through environment may enhance the effects of the radiation on the sample material. Further, in flow-through or single batch arrangements, sample material may be retained exterior to or within a processing chamber by one or more retaining members (e.g., filter, valve, etc.) until a characteristic of the sample material reaches one or more particular criteria (e.g., physical, chemical, biological). Once the criteria of the sample material is attained (e.g., via further treatment), the material is then permitted to flow past the retaining member(s) and through the inlet or outlet of the chamber.

Abstract: The present invention relates to systems for releasing genetic materials from a solid medium. The present invention also relates to methods for releasing genetic materials from a solid medium. The present invention further relates to methods for isolating genetic material from a biological sample.

Abstract: A method for sorting particles, in particular cells A and B. The method uses a single channel with only one input and only one output. A particle mix A and B in a fluid is introduced into the channel and particles within the channel are sorted.

Abstract: The present invention is directed to a method of making a stable composition comprising growth factors, which may include platelet derived growth factors and transforming growth factors. The method comprises providing human umbilical cord blood plasma containing platelets, but substantially free of whole blood cells, and lysing the platelets to extrude growth factors into the plasma. The plasma may be obtained from multiple donors and pooled to form a homologous plasma mixture. In another embodiment, the growth factors are encapsulated in a liposome formed by a lipid bilayer, wherein the resulting composition remains stable and viable for at least 30 months. The present invention is also directed to the composition produced by the methods of the present invention and the process of applying the composition to a skin defect or wound.

Abstract: A micro-device for disrupting cells includes a first chamber in which the cells are disrupted, a second chamber which is pressurized and depressurized, a flexible membrane which separates the first chamber and the second chamber and is vibrated by pressuring and depressurizing the second chamber, and a micro-unit confined in the first chamber, where the micro-unit disrupts the cells in the first chamber.

Abstract: The invention relates to the cell disruption of microbes and the preparation of the microbe proteins for mass spectrometric analysis. The cells of microbes from microcolonies are disrupted by physical or chemical means directly on the nutrient medium. The released proteins are then transferred to sample supports by direct contact with their contact surfaces; electrophoresis can be used for assistance. Once the proteins are firmly adsorbed on the contact surfaces, they can be washed with water in order to remove substances which interfere with the ionization process. For analysis by matrix-assisted laser desorption (MALDI), the proteins are prepared on the contact surfaces of the sample supports with matrix substances to form MALDI samples; the sample supports are then introduced into a MALDI mass spectrometer for the acquisition of mass spectra. The microbes are identified by similarity comparisons between the mass spectra of the microbe proteins and similarly obtained reference spectra.

Abstract: The invention concerns a device and a method for concentrating pathogenic germs potentially present in blood products or derivatives and for detecting said germs comprising the following steps: (a) subjecting a sample of said blood product to a blood cell aggregating treatment, (b) eliminating the aggregates formed at step (a) by passing the treated sample over a first filter allowing through the contaminating germs but not the cell aggregates, (c) selectively lyzing the residual cells of the filtrate obtained at step (b), (d) recuperating the contaminating germs by passing the lysate of step (c) over a second filter to detect the contaminating germs possibly trapped.

Abstract: A system and method for sonication of multiple samples and continuous sonication of an input fluid stream in flow-through arrangements useful for economical breakdown of particulates and organisms present in large volumes with relatively low-power sonication devices such as production of oil from algae. The system includes an electrical wave generator oscillating in the ultrasound range, a vibrating element electrically connected to the electrical wave generator, and a sonication plate that vibrates in certain modes. The sonication plate contains features for mating with sample tubes, and the sample tubes also possess complimentary mating features to those on the sonication plate. A method for sonication of multiple samples includes utilizing mating features to attach tubes to the sonication plate and energizing the sonicator to vibrate the sonication plate. The invention also relates to arrangements for continuous flow-through useful for sonicating large sample volumes.

Abstract: According to one embodiment, the disclosure provides a system for algal cell lysis. The system may include at least one algal cell, a plurality of metal nanoparticles, and an electromagnetic radiation generator. The generator may be able to generate radio frequency or microwave radiation that excites the plurality of metal nanoparticles, resulting in lysis of the algal cell. The disclosure also provides a system for recovery of a lipid from an algal cell similar to the above system but also including a separator. The disclosure further provides a method of recovering a lipid from an algal cell by supplying a plurality of metal nanoparticles to at least one algal cell, exciting the plurality of metal nanoparticles with radio frequency or microwave electromagnetic radiation, lysing the algal cell to release the lipid, and separating the lipid from the lysed algal cell.

Abstract: To provide a system by which evaluation of circumstances of contamination by microparticles having nucleic acid can be performed rapidly and accurately. The theme is achieved by a system for measuring microparticles that includes: (1) a microparticle adhesion step of adhering the microparticles having nucleic acid to a microparticle adhesion member; (2) a membrane breakage step of breaking membranes of the adhered microparticles by electrical discharge; (3) an electrophoresis step of electrophoresing the microparticles in a thickness direction of a gel to make the nucleic acid in the microparticles migrate from a negative electrode side toward a positive electrode side and adhere the nucleic acid on a surface of a nucleic acid detection member; and (4) a nucleic acid measurement step of fluorescently staining the surface of the nucleic acid detection member to measure a concentration of the nucleic acid.

Abstract: Contemplated methods and devices are drawn to preparation and analysis of analytes from biological samples. In a preferred embodiment the analytes are nucleic acids that are both released from biological compartment present in the sample and fragmented through the use of a voltage potential applied to a pair of electrodes. The nucleic acids thus prepared are subsequently characterized.

Abstract: The present invention relates to a non-destructive process for the preparation of amoebocyte lysate from the haemolymph of horseshoe crab, characterized by the steps of firstly, means for acclimatizing a live specimen of horseshoe crab in treated seawater under controlled conditions; then, means for cleaning the live specimen, including cleaning the base of the last pair of thoracic appendages of the live specimen; next, means for withdrawing the haemolymph through the base of the last pair of thoracic appendage under aseptic condition; then, means for transferring the collected haemolymph into a pre-cooled disposable centrifuge tube; then, means for centrifuging the collected haemolymph to separate amoebocyte cells from lymph; then, means for decanting the lymph out of the disposable centrifuge tube; then, means for washing the white amoebocyte cells and centrifuging; then, means for sonicating the amoebocyte cells for lysing of the amoebocyte cells; then, means for storing the sonicated amoebocyte cells for

Abstract: According to one embodiment, the disclosure provides a system for algal cell lysis. The system may include at least one algal cell, a plurality of metal nanoparticles, and an electromagnetic radiation generator. The generator may be able to generate radio frequency or microwave radiation that excites the plurality of metal nanoparticles, resulting in lysis of the algal cell. The disclosure also provides a system for recovery of a lipid from an algal cell similar to the above system but also including a separator. The disclosure further provides a method of recovering a lipid from an algal cell by supplying a plurality of metal nanoparticles to at least one algal cell, exciting the plurality of metal nanoparticles with radio frequency or microwave electromagnetic radiation, lysing the algal cell to release the lipid, and separating the lipid from the lysed algal cell.

Abstract: Described are methods of cultivating autotrophic microorganisms, particularly microalgae or diatoms, in a bioreactor by entraining a culture of the microorganisms in a tenuous, gelated, thixotrophic carrier medium having nutrients therefor and moving the medium along a passage at a sufficiently slow speed to enable laminar flow which in cross section is closed and which has transparent walls through which the culture is irradiated to enable photosynthesis. The method includes effecting convective turnover of the culture and medium as they flow along the passage by differentially heating the medium laterally relative to the flow direction so as to produce a generally helical flow of the culture and medium. Also described are processing methods, both physical and chemical, performed underground e.g.

Abstract: A device configured for lysing a sample includes a holding element configured to hold an energy-transmitting element such that the holding element lies around the held part of the energy-transmitting element and envelops the held part of the energy-transmitting element and/or that the holding element lies against the held part of the energy-transmitting element. The holding element is further configured to cause lysis with the energy-transmitting element when the holding element is immersed into the sample to be subjected to lysis or comes into contact with the sample to be subjected to lysis. A method includes inserting the energy-transmitting element into the holding element. A system configured for lysing a sample by way of ultrasound includes the device and the energy transmitting element.

Abstract: A bioreactor system for growing commercial volumes of algae or other biomass in an enclosed, biosecure reactor vessel, the system having internal artificial growth light production as well as exterior solar energy capturing devices or the like designed to facilitate enhanced sunlight exposure for photosynthesis organism production. Magnetic and electromagnetic field generation systems and/or millimeter wave generating devices are integrated with the bioreactor system and its operation to substantially enhance growth rate and overall productivity.

Abstract: A liquid sample flow containing living cells is irradiated with measurement laser light and the photo data of at least either scattering light or fluorescence that is generated by each of the living cells in the liquid sample flow due to the irradiation with the measurement laser light is acquired. Based on the photo data thus acquired, it is determined whether each of the cells assignable to the respective photo data is an unnecessary living cell or a target living cell. Based on the determination results, a pulse voltage is then applied exclusively to the living cells having been determined as unnecessary living cells so that the unnecessary living cells are damaged and killed.

Abstract: The present invention relates to a method by which a controlled source of heat (preferably a laser 3) generates a pulsating vapor bubble 4 in an enclosed liquid. The pulsating rate (the frequency) is preferably in the ultrasonic region, whereby cavitation occurs in the liquid. The cavitation effect will cause disruption of suspended components such as cells or bacterial spores. The ultrasonic disruption of cellular components is known as lysing by sonication.

Abstract: A method for irradiating a sample with focused acoustic energy is provided. The generated acoustic energy is transmitted from the source to the sample via a completely dry propagation path. At least two different focal regions are generated with the source for generating acoustic energy.

Abstract: In this invention, a novel protein interaction domain is provided along with several of its variants. This domain is involved in protein-protein interactions with the Bcl-2 family of proteins. It is named BLID (Bcl2 family of proteins Like Interaction Domain). Use of BLID and its variants for modulating cellular activity is presented. BLID, its variants and or anti-BLID antibodies could be useful as a screening tool as well as for discovery of drugs that help fight pathological states like degenerative diseases, cerebral or cardiac ischemic hypoxic disorders, cancer and autoimmunity.

Abstract: Microorganisms such as microalgae are collected and separated from a host medium such as water. Cellular walls and membranes of the microorganisms are then ruptured to release their lipids using a lipid extraction unit. Thereafter, the lipids from the host medium are collected and separated using a lipid collection and separation unit. Related apparatus, systems, techniques and articles are also described.

Abstract: Hemoglobin in a sample solution is quickly and reliably denatured; at the same time, quick and accurate measurement of hemoglobin and a hemoglobin derivative is realized. In a method for measuring hemoglobin and a hemoglobin derivative, and a reagent composition, a measurement kit, an analysis device, and an analysis system used in the method, a sample solution containing a blood component is treated with a nonionic surfactant, an oxidizing agent, and a metal salt to denature hemoglobin in the sample solution to measure the hemoglobin, and thereafter the amount of a hemoglobin derivative in the sample is measured by an immunological method using an antibody specifically binding to a denatured site of the denatured hemoglobin derivative.